|
1
|
Gagnière M, Daste C, Campagna R, Drapé JL, Feydy A, Guerini H, Lefèvre-Colau MM, Rannou F, Nguyen C. Efficacy and safety of intra-articular botulinum toxin injection therapy for joint pain: A systematic review and meta-analysis. Ann Phys Rehabil Med 2025; 68:101877. [PMID: 39647305 DOI: 10.1016/j.rehab.2024.101877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 06/06/2024] [Accepted: 06/12/2024] [Indexed: 12/10/2024]
Abstract
BACKGROUND Studies conducted in various animal models of joint pain showed an anti-nociceptive effect of intra-articular botulinum toxin type A (BoNT-A). Randomized controlled trials (RCTs) in humans suggest a potential effect but results are disparate. OBJECTIVES To assess the efficacy and safety of intra-articular BoNT-A for the treatment of joint pain. METHODS We conducted a systematic review of RCTs comparing the effects of intra-articular BoNT-A to other interventions on pain and activity limitations in the short (<3 months), intermediate (3-6 months) and long term (> 6 months), and their adverse effects, in people with joint pain. We performed a meta-analysis when appropriate. MEDLINE, EMBASE, ClinicalTrials.gov, CINHAL and ICTRP databases were searched from inception to July 9, 2023. Two independent reviewers selected eligible studies and extracted data in a standardized manner. The results of quantitative synthesis were expressed as the standardized mean difference (SMD) (95 % confidence interval). RESULTS We included 14 RCTs: 437 participants received an intra-articular injection of BoNT-A and 551 received another intervention. Overall, 7 RCTs (549 participants) compared intra-articular BoNT-A with an intra-articular treatment in the knee: short-, intermediate-, and long-term SMD were -0.35 (-0.82 to 0.12), -0.27 (-0.61 to 0.08), and -0.43 (-1.12 to 0.26) for pain and -0.44 (-0.96 to 0.07), -0.24 (-0.63 to 0.15) and -0.42 (-1.26 to 0.42) for activity limitations, respectively. Two RCTs (68 participants) in the shoulder and 1 RCT (60 participants) in the base-of-thumb showed reduced pain in the short term. Minor adverse events were not rare, but no serious adverse events related to intra-articular BoNT-A were reported. CONCLUSIONS Intra-articular BoNT-A may reduce joint pain in the short term for small and medium-sized joints (ie, base-of-thumb and shoulder), but not for large joints (ie, knee). REGISTRATION PROSPERO: CRD42021290157 (Date of first submission: 8 November 2021; Date of registration: 8 December 2021).
Collapse
Affiliation(s)
- Mathieu Gagnière
- AP-HP.Centre-Université Paris Cité, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Camille Daste
- AP-HP.Centre-Université Paris Cité, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, Faculté de Santé, UFR de Médecine, 15 Rue de l'École de Médecine, 75006 Paris, France
| | - Raphaël Campagna
- AP-HP.Centre-Université Paris Cité, Service de Radiologie B, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Jean-Luc Drapé
- Université Paris Cité, Faculté de Santé, UFR de Médecine, 15 Rue de l'École de Médecine, 75006 Paris, France; AP-HP.Centre-Université Paris Cité, Service de Radiologie B, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique, ECaMO Team, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Antoine Feydy
- Université Paris Cité, Faculté de Santé, UFR de Médecine, 15 Rue de l'École de Médecine, 75006 Paris, France; AP-HP.Centre-Université Paris Cité, Service de Radiologie B, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique, ECaMO Team, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Henri Guerini
- AP-HP.Centre-Université Paris Cité, Service de Radiologie B, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Marie-Martine Lefèvre-Colau
- AP-HP.Centre-Université Paris Cité, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, Faculté de Santé, UFR de Médecine, 15 Rue de l'École de Médecine, 75006 Paris, France; INSERM UMR-S 1153, Centre de Recherche Épidémiologie et Statistique, ECaMO Team, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; Fédération pour la Recherche sur le Handicap et l'Autonomie, mie, 8 rue de la Croix de Jarry, Bat. A, 75013 Paris, France
| | - François Rannou
- AP-HP.Centre-Université Paris Cité, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, Faculté de Santé, UFR de Médecine, 15 Rue de l'École de Médecine, 75006 Paris, France; INSERM UMR-S 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs (T3S), Campus Saint-Germain-des-Prés, 45 Rue des Saints-Pères, 75006 Paris, France
| | - Christelle Nguyen
- AP-HP.Centre-Université Paris Cité, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpital Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, Faculté de Santé, UFR de Médecine, 15 Rue de l'École de Médecine, 75006 Paris, France; INSERM UMR-S 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs (T3S), Campus Saint-Germain-des-Prés, 45 Rue des Saints-Pères, 75006 Paris, France.
| |
Collapse
|
|
2
|
Ferraro GA, Mattiello S, Natriello A, Lanzano G, Nicoletti GF. Botulinum Toxin-A Infiltration to Control Post-Operative Pain after Mastectomy and Expander Reconstruction as Potentially Useful Tool: A Narrative Review. Aesthetic Plast Surg 2024; 48:4930-4936. [PMID: 38722336 DOI: 10.1007/s00266-024-04034-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 03/19/2024] [Indexed: 01/19/2025]
Abstract
Botulinum toxin-A (BTX-A), a neurotoxin produced by Clostridium botulinum, was assessed for relieving implant-related pectoralis major muscle's painful spasms. In detail, 100 units of BTX-A can reduce muscle activity and, as a consequence, muscle spasms. The latter is considered the leading cause of post-operative pain after the sub-pectoral tissue expansion, sometimes leading to early expanders' removal. In addition, women choosing post-mastectomy reconstruction surgery seem to suffer worse post-operative pain than those who stop at the mastectomy stage. However, there is no unanimous consensus concerning the potential benefits of BTX-A in reducing pain related to the sub-pectoral placement of tissue expanders in breast reconstruction due to the exiguity of evidence. Therefore, this review aims to describe BTX-A-related evidence in this reconstruction setting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Collapse
Affiliation(s)
- Giuseppe Andrea Ferraro
- Multidisciplinary Department of Medical and Dental Specialties, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
| | - Sara Mattiello
- Multidisciplinary Department of Medical and Dental Specialties, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy
| | - Arcangelo Natriello
- Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy
| | - Giuseppe Lanzano
- Multidisciplinary Department of Medical and Dental Specialties, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy
| | - Giovanni Francesco Nicoletti
- Multidisciplinary Department of Medical and Dental Specialties, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy
| |
Collapse
|
|
3
|
Poenaru D, Sandulescu MI, Cinteza D. Pain Modulation in Chronic Musculoskeletal Disorders: Botulinum Toxin, a Descriptive Analysis. Biomedicines 2023; 11:1888. [PMID: 37509527 PMCID: PMC10376837 DOI: 10.3390/biomedicines11071888] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/25/2023] [Accepted: 07/01/2023] [Indexed: 07/30/2023] Open
Abstract
Botulinum neurotoxin (BoNT), a product of Clostridium botulinum, reversibly inhibits the presynaptic release of the neurotransmitter acetylcholine at the neuromuscular junction. In addition, BoNT blocks the transmission of other substances involved in pain perception and, together with a soft-tissue anti-inflammatory effect, may play a role in analgesia. When first-line treatment fails, second-line therapies might include BoNT. Studies on chronic and recurrent pain using different mechanisms offer heterogenous results that must be validated and standardized. Plantar fasciitis, severe knee osteoarthritis, painful knee and hip arthroplasty, antalgic muscular contractures, and neuropathic and myofascial pain syndromes may benefit from the administration of BoNT. Research on this topic has revealed the main musculoskeletal conditions that can benefit from BoNT, stressing the effects, modalities of administration, doses, and schedule.
Collapse
Affiliation(s)
- Daniela Poenaru
- Rehabilitation Department 1, Carol Davila University of Medicine and Pharmacy, 4192910 Bucharest, Romania
| | - Miruna Ioana Sandulescu
- Doctoral School, Carol Davila University of Medicine and Pharmacy, 4192910 Bucharest, Romania
| | - Delia Cinteza
- Rehabilitation Department 1, Carol Davila University of Medicine and Pharmacy, 4192910 Bucharest, Romania
| |
Collapse
|
|
4
|
Béret M, Barry F, Garcia-Fernandez MJ, Chijcheapaza-Flores H, Blanchemain N, Chai F, Nicot R. Efficacy of Intra-Articular Injection of Botulinum Toxin Type A (IncobotulinumtoxinA) in Temporomandibular Joint Osteoarthritis: A Three-Arm Controlled Trial in Rats. Toxins (Basel) 2023; 15:toxins15040261. [PMID: 37104199 PMCID: PMC10142654 DOI: 10.3390/toxins15040261] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/27/2023] [Accepted: 03/28/2023] [Indexed: 04/05/2023] Open
Abstract
Temporomandibular disorders (TMD) are complex pathologies responsible for chronic orofacial pain. Intramuscular injection of botulinum toxin A (BoNT/A) has shown effectiveness in knee and shoulder osteoarthritis, as well as in some TMDs such as masticatory myofascial pain, but its use remains controversial. This study aimed to evaluate the effect of intra-articular BoNT/A injection in an animal model of temporomandibular joint osteoarthritis. A rat model of temporomandibular osteoarthritis was used to compare the effects of intra-articular injection of BoNT/A, placebo (saline), and hyaluronic acid (HA). Efficacy was compared by pain assessment (head withdrawal test), histological analysis, and imaging performed in each group at different time points until day 30. Compared with the rats receiving placebo, those receiving intra-articular BoNT/A and HA had a significant decrease in pain at day 14. The analgesic effect of BoNT/A was evident as early as day 7, and lasted until day 21. Histological and radiographic analyses showed decrease in joint inflammation in the BoNT/A and HA groups. The osteoarthritis histological score at day 30 was significantly lower in the BoNT/A group than in the other two groups (p = 0.016). Intra-articular injection of BoNT/A appeared to reduce pain and inflammation in experimentally induced temporomandibular osteoarthritis in rats.
Collapse
Affiliation(s)
- Marie Béret
- Univ. Lille, INSERM, U1008-Advanced Drug Delivery Systems, F59000 Lille, France
| | - Florent Barry
- Univ. Lille, CHU Lille, INSERM, Department of Oral and Maxillofacial Surgery, U1008-Advanced Drug Delivery Systems, F59000 Lille, France
| | | | | | - Nicolas Blanchemain
- Univ. Lille, INSERM, U1008-Advanced Drug Delivery Systems, F59000 Lille, France
| | - Feng Chai
- Univ. Lille, INSERM, U1008-Advanced Drug Delivery Systems, F59000 Lille, France
| | - Romain Nicot
- Univ. Lille, CHU Lille, INSERM, Department of Oral and Maxillofacial Surgery, U1008-Advanced Drug Delivery Systems, F59000 Lille, France
| |
Collapse
|
|
5
|
Wang C, Zhao J, Gao F, Jia M, Hu L, Gao C. The efficacy and safety of intra-articular botulinum toxin type A injection for knee osteoarthritis: A meta-analysis of randomized controlled trials. Toxicon 2023; 224:107026. [PMID: 36640812 DOI: 10.1016/j.toxicon.2023.107026] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 12/24/2022] [Accepted: 01/10/2023] [Indexed: 01/13/2023]
Abstract
The purpose of this study was to investigate the efficacy and safety of intra-articular Botulinum Toxin type A (BTA) injection in the management of patients with knee osteoarthritis (KOA). The literature retrieval was conducted based on PRISMA guidelines. Databases including Pubmed, Web of science, EMBASE, and Cochrane Library were searched to identify RCTs that comparing the effects of intra-articular BTA injection with control interventions on patients with KOA. The primary outcomes involved pain and function improvements as well as the occurrence of adverse events. Seven RCTs comprising 548 participants were included in this meta-analysis. Compared with the control group, BTA injection exhibited greater pain reduction at 4 weeks posttreatment (SMD = -0.86, 95% CI [-1.52, -0.19], p = 0.011), but not 8-24 weeks posttreatment (wk 8, SMD = -0.53, 95% CI [-1.21, 0.15], p = 0.127; wk 12, SMD = -0.34, 95% CI [-0.73, 0.04], p = 0.081; wk 24, SMD = -0.65, 95% CI [-1.52, 0.22], p = 0.144). Additionally, no differences were found between BTA injection versus control intervention on functional improvement at all time points assessed (wk 4, WMD = -5.16, 95% CI [-12.31, 2.00], p = 0.158; wk 8, WMD = -0.98, 95% CI [-5.66, 3.71], p = 0.683; wk 12, WMD = -2.52, 95% CI [-7.54, 2.50], p = 0.325); wk 24, WMD = -3.66, 95% CI [-14.09, 6.76], p = 0.491). There was no significant difference in adverse event rate between the BTA and control group (OR = 0.88, 95% CI [0.24, 3.18], p = 0.843). This meta-analysis suggests that intra-articular BTA injection could be an efficious and safe strategy for analgesic treatment of KOA. However, evidence is limited due to the small number and heterogeneity of included studies, this urges further and stronger trials to confirm our findings.
Collapse
Affiliation(s)
- Chen Wang
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Jinpeng Zhao
- Department of Cardiothoracic Surgery, Yantai Municipal Laiyang Central Hospital, Yantai, Shandong, China
| | - Fang Gao
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Min Jia
- Department of Rehabilitation Medicine, Jinan Municipal Hospital of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Luoman Hu
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Chengfei Gao
- Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
| |
Collapse
|
|
6
|
Sconza C, Leonardi G, Carfì C, Kon E, Respizzi S, Scaturro D, Letizia Mauro G, Massazza G, Di Matteo B. Intra-Articular Injection of Botulinum Toxin for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials. Int J Mol Sci 2023; 24:ijms24021486. [PMID: 36674999 PMCID: PMC9863806 DOI: 10.3390/ijms24021486] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/18/2022] [Accepted: 01/09/2023] [Indexed: 01/15/2023] Open
Abstract
The purpose of the present paper was to review the available evidence on intra-articular botulinum toxin (BTX) injection in the treatment of knee osteoarthritis and to compare it to other conservative treatment options. A systematic review of the literature was performed on the PubMed, Scopus, Cochrane Library, Web of Science, Pedro and Research Gate databases with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in the English language, and (3) published on indexed journals in the last 20 years (2001-2021) dealing with the use of BTX intra-articular injection for the treatment of knee OA. The risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. Nine studies involving 811 patients in total were included. Patients in the control groups received different treatments: conventional physiotherapy, hyaluronic acid injection or prolotherapy or a combination thereof in 5 studies, steroid infiltrative therapy (triamcinolone) in 1 study, placebo in 2, and local anesthetic treatment in 1 study. Looking at the quality of the available literature, two of the included studies reached "Good quality" standard, three were ranked as "Fair", and the rest were considered "Poor". No major complications or serious adverse events were reported following intra-articular BTX, which provided encouraging pain relief, improved motor function, and quality of life. Based on the available data, no clear indication emerged from the comparison of BTX with other established treatments for knee OA. The analysis of the available RCTs on BTX intra-articular injection for the treatment of knee OA revealed modest methodological quality. However, based on the data retrieved, botulinum toxin has been proven to provide good short-term outcomes, especially in patients with pain sensitization, by modulating neurotransmitter release, peripheral nociceptive transduction, and acting on the control of chronic pain from central sensitization.
Collapse
Affiliation(s)
- Cristiano Sconza
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Giulia Leonardi
- U.O.C. of Physical and Rehabilitation Medicine and Sports Medicine, Policlinico Universitario “G. Martino”, 98124 Messina, Italy
| | - Carla Carfì
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Elizaveta Kon
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Correspondence: ; Tel.: +39-028-224-5425; Fax: +39-028-224-4600
| | - Stefano Respizzi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Dalila Scaturro
- Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Via del Vespro, 129, 90127 Palermo, Italy
| | - Giulia Letizia Mauro
- Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Via del Vespro, 129, 90127 Palermo, Italy
| | - Giuseppe Massazza
- Division of Physical Medicine and Rehabilitation, Department of Surgical Sciences, University of Turin, 10124 Turin, Italy
| | - Berardo Di Matteo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| |
Collapse
|
|
7
|
Sari BC, Develi T. The effect of intraarticular botulinum toxin-A injection on symptoms of temporomandibular joint disorder. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2022; 123:e316-e320. [PMID: 35523405 DOI: 10.1016/j.jormas.2022.04.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 04/25/2022] [Accepted: 04/26/2022] [Indexed: 06/14/2023]
Abstract
INTRODUCTION Application of arthrocentesis in temporomandibular joint disorders preferred and suggested therapeutic treatment option in recent years. This study was designed to investigate and compare the effect of intra-articular injection of botulinum toxin-A (Btx-A) on pain and mouth opening after arthrocentesis in nonreduction disc displacement. MATERIALS AND METHODS This restrospective study was conducted on 30 patients with a visual analogue scale is higher than five and limited mouth opening. Patients were divided into 2 groups as conventional arthrocentesis group (group A) and intra-articular Btx-A injection following arthrocentesis group (group B). Maximum mouth openining and temporomandibular joint pain were measured in preoperative (t0) and at postoperative 1st-week (t1), 1st-month (t2) and 6th-month (t3). RESULTS When VAS scores of group A and group B were examined, no statistical difference was observed at t0 and t1 time intervals; an increased in mouth opening values and decreased VAS score values were observed in both groups in the 1st month (t2) and 6th (t3) months, mostly in group A. CONCLUSION İntra-articular injection of Btx-A following arthrocentesis can induce mouth opening and reduce the pain and dysfunction in patients with anterior disc displacement.
Collapse
Affiliation(s)
- Bilal Cemsit Sari
- Department of Oral and Maxillofacial Surgery, Istanbul Medipol University Faculty of Dentistry, Istanbul, Turkey.
| | - Tuba Develi
- Department of Oral and Maxillofacial Surgery, Istanbul Medipol University Faculty of Dentistry, Istanbul, Turkey
| |
Collapse
|
|
8
|
Quaranta M, Riccio I, Oliva F, Maffulli N. Osteoarthritis of the Knee in Middle-age Athletes: Many Measures are Practiced, but Lack Sound Scientific Evidence. Sports Med Arthrosc Rev 2022; 30:102-110. [PMID: 35533062 DOI: 10.1097/jsa.0000000000000341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Osteoarthritis of the knee generally affects individuals from the fifth decade, the typical age of middle-age athletes. In the early stages, management is conservative and multidisciplinary. It is advisable to avoid sports with high risk of trauma, but it is important that patients continue to be physically active. Conservative management offers several options; however, it is unclear which ones are really useful. This narrative review briefly reports the conservative options for which there is no evidence of effectiveness, or there is only evidence of short-term effectiveness.
Collapse
Affiliation(s)
- Marco Quaranta
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi
- Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
| | - Ivano Riccio
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi
- Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
| | - Francesco Oliva
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi
- Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Baronissi
- Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
- Barts and the London School of Medicine and Dentistry, Centre for Sports and Exercise Medicine, Mile End Hospital, Queen Mary University of London, London
- Faculty of Medicine, School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Stoke-on-Trent, England
| |
Collapse
|
|
9
|
Lee BJ, Park D. Botulinum Toxin Injection of a Patient with Intractable Acromio-Clavicular Joint Pain due to Distal Clavicular Osteolysis. PAIN MEDICINE 2020; 21:3730-3732. [PMID: 32289822 DOI: 10.1093/pm/pnaa066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Byung Joo Lee
- Department of Rehabilitation Medicine, Daegu Fatima Hospital, Daegu, Republic of Korea
| | - Donghwi Park
- Department of Physical Medicine and Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, Dong-gu, Ulsan, Republic of Korea
| |
Collapse
|
|
10
|
Botulinum Toxin A in Tissue Expander Breast Reconstruction: A Double-blinded Randomized Controlled Trial. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2020; 8:e3030. [PMID: 32983785 PMCID: PMC7489665 DOI: 10.1097/gox.0000000000003030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 06/11/2020] [Indexed: 11/25/2022]
Abstract
Subpectoral tissue expander breast reconstruction is often associated with muscle spasms, pain, and discomfort during tissue expansion. In this study, we hypothesized that an intraoperative injection of botulinum toxin A (BTX-A) in the pectoralis major muscle reduces the pain associated with tissue expansion and improves women's physical well-being. Methods Between May 2012 and May 2017, women undergoing immediate subpectoral tissue expander breast reconstruction were randomized to administer 100 units of BTX-A or a placebo injection. A numeric pain intensity scale and the physical well-being scale of the BREAST-Q: Reconstruction Module were used to test our hypothesis. Data on postoperative oral narcotic consumption were not collected. Results Of the 131 women included in the analysis, 48% were randomized to placebo and 52% to BTX-A. The preoperative median pain intensity score was 0 [interquartile range (IQR), 0-1], and the median preoperative BREAST-Q score was 91 (IQR, 81-100). The median slopes for the change in pain intensity scores from baseline throughout tissue expansion for those randomized to placebo and BTX-A were -0.01 (IQR, -0.02 to 0.00) and -0.01 (IQR, -0.02 to 0.00), respectively (P = 0.55). The median slopes for the change in BREAST-Q scores from baseline throughout tissue expansion for those randomized to placebo and BTX-A were 0.04 (IQR, -0.17 to 0.14) and 0.02 (IQR, -0.06 to 0.13), respectively (P = 0.89). Conclusion In this study, we found that an intraoperative intramuscular injection of 100 units of BTX-A in the pectoralis major muscle did not reduce postoperative pain and patient-reported physical well-being when compared with placebo.
Collapse
|
|
11
|
Blanshan N, Krug H. The Use of Botulinum Toxin for the Treatment of Chronic Joint Pain: Clinical and Experimental Evidence. Toxins (Basel) 2020; 12:toxins12050314. [PMID: 32397671 PMCID: PMC7291335 DOI: 10.3390/toxins12050314] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 04/25/2020] [Accepted: 05/05/2020] [Indexed: 12/11/2022] Open
Abstract
Chronic osteoarthritis pain is an increasing worldwide problem. Treatment for osteoarthritis pain is generally inadequate or fraught with potential toxicities. Botulinum toxins (BoNTs) are potent inhibitors of neuropeptide release. Paralytic toxicity is due to inhibition at the neuromuscular junction, and this effect has been utilized for treatments of painful dystonias. Pain relief following BoNT muscle injection has been noted to be more significant than muscle weakness and hypothesized to occur because of the inhibition of peripheral neuropeptide release and reduction of peripheral sensitization. Because of this observation, BoNT has been studied as an intra-articular (IA) analgesic for chronic joint pain. In clinical trials, BoNT appears to be effective for nociceptive joint pain. No toxicity has been reported. In preclinical models of joint pain, BoNT is similarly effective. Examination of the dorsal root ganglion (DRG) and the central nervous system has shown that catalytically active BoNT is retrogradely transported by neurons and then transcytosed to afferent synapses in the brain. This suggests that pain relief may also be due to the central effects of the drug. In summary, BoNT appears to be safe and effective for the treatment of chronic joint pain. The long-term effects of IA BoNT are still being determined.
Collapse
Affiliation(s)
- Nicole Blanshan
- Minneapolis VA Health Care System, Minneapolis, MN 55455, USA;
| | - Hollis Krug
- Minneapolis VA Health Care System, Minneapolis, MN 55455, USA;
- Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
- Correspondence: ; Tel.: +1-612-467-4190
| |
Collapse
|
|
12
|
Hsu PC, Wu WT, Han DS, Chang KV. Comparative Effectiveness of Botulinum Toxin Injection for Chronic Shoulder Pain: A Meta-Analysis of Randomized Controlled Trials. Toxins (Basel) 2020; 12:toxins12040251. [PMID: 32290577 PMCID: PMC7232231 DOI: 10.3390/toxins12040251] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 04/09/2020] [Accepted: 04/10/2020] [Indexed: 12/16/2022] Open
Abstract
Botulinum toxin (BoNT) injection is regarded as a promising treatment for musculoskeletal pain. However, its efficacy for treating chronic shoulder pain remains unclear. We investigated the effectiveness of BoNT injections for chronic shoulder pain by conducting a systematic search of electronic databases up to March 2020 for randomized control trials (RCTs) that used BoNT injections for chronic shoulder pain treatment. The primary outcome was the between-group comparison of pain reduction, quantified by the standardized mean difference (SMD). Nine RCTs comprising 666 patients were included and divided into two groups: one group with shoulder joint pain (n = 182) and the other group with shoulder myofascial pain (n = 484). Regarding shoulder joint pain, the efficacy of BoNT injections was similar to that of the reference treatment (SMD: −0.605, 95% confidence level [CI]: −1.242 to 0.032 versus saline; SMD: −0.180, 95% CI: −0.514 to 0.153 versus corticosteroids) at one month post-intervention, and was superior (SMD: −0.648, 95% CI: −0.1071 to −0.225 versus corticosteroids) between one and three months. Likewise, in terms of shoulder myofascial pain, the effectiveness of BoNT injections did not differ from the reference treatment (SMD: −0.212, 95% CI: −0.551 to 0.127 versus saline; SMD: 0.665, 95% CI: −0.260 to 1.590 versus dry needling and SMD: 1.093; 95% CI: 0.128 to 2.058 versus lidocaine) at one month post- intervention, and appeared superior (SMD: −0.314, 95% CI: −0.516 to −0.111 versus saline) between one and three months. Our meta-analysis revealed that BoNT injections could be a safe and effective alternative for patients with chronic shoulder pain.
Collapse
Affiliation(s)
- Po-Cheng Hsu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei 10845, Taiwan; (P.-C.H.); (W.-T.W.); (D.-S.H.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
| | - Wei-Ting Wu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei 10845, Taiwan; (P.-C.H.); (W.-T.W.); (D.-S.H.)
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei 10048, Taiwan
| | - Der-Sheng Han
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei 10845, Taiwan; (P.-C.H.); (W.-T.W.); (D.-S.H.)
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei 10048, Taiwan
| | - Ke-Vin Chang
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei 10845, Taiwan; (P.-C.H.); (W.-T.W.); (D.-S.H.)
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei 10048, Taiwan
- Correspondence: ; Tel.: +886-2-2371-7101
| |
Collapse
|
|
13
|
Efficacy of Intra-Articular Botulinum Toxin in Osteoarticular Joint Pain: A Meta-Analysis of Randomized Controlled Trials. Clin J Pain 2019; 34:383-389. [PMID: 28731959 DOI: 10.1097/ajp.0000000000000538] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE This study was conducted with the aim of evaluating the efficacy of intra-articular injections of botulinum toxin type A (BT-A) into the painful joint diseases through a systematic review of the literature and a meta-analysis of controlled randomized trials. Intra-articular therapies (corticosteroids, hyaluronic acid) have limited efficacy and run a risk of toxicity in patients with joint pain. New therapeutic options are needed to treat painful osteoarticular disease. METHODS We searched via Pubmed, American College of Rheumatology, and European League Against Rheumatism congresses, and gray literature for the studies reported until June 2016 and addressing the issue of BT intra-articular injections in patients with refractory joint pain. Randomized trials were included. For the meta-analysis, we compared a numeric rating scale (NRS) from 0 to 10 before treatment and at 1 or 2 months and 6 months after in the BT-A and the control groups for each study. We also compared separately low dose and high dose of BT at 1 or 2 months' evaluation. RESULTS In a total of 269 selected articles, 8 were analyzed and 6 studies were included in the meta-analysis involving a total of 382 patients. On comparing the NRS rating for 5 trials, at 1 or 2 months irrespective of the dose of BT, 4 trials showed a positive effect of BT compared with the control on the NRS and 1 found no effect; the overall weighted mean difference [95% confidence interval (CI)] was -1.10 (-1.62, -0.58) (P<0.0001, I=63%). Among the 4 trials with a low dose of BT (100 U), comparing NRS at 1 or 2 months, 3 trials showed significant results with a positive effect of BT-A injection compared with the control on the NRS; the fourth study failed to find any effect. The overall weighted mean difference (95% CI) was -0.95 (-0.02, -1.88) (P=0.05, I=67%). In the 2 trials using a high dose of BT (200 U) comparing NRS at 1 or 2 months, there was an almost zero effect of BT, with an overall weighted mean difference (95% CI) of 0.13 (-0.55, 0.81) (P=0.71, I=0%). In the 3 trials comparing NRS at 6 months there was an overall weighted mean difference (95% CI) of -0.57 (-1.98, 0.83) (P=0.42, I=73%). CONCLUSIONS BT-A intra-articular injections have short-term benefits with a statistically significant decrease in the NRS pain score of around 1 point in patients with refractory joint pain. A decrease in the pain score was also observed at 6 months but with a nonsignificant result.
Collapse
|
|
14
|
Bellon G, Venturin A, Masiero S, Del Felice A. Intra-articular botulinum toxin injection in complex regional pain syndrome: Case report and review of the literature. Toxicon 2019; 159:41-44. [DOI: 10.1016/j.toxicon.2019.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 12/29/2018] [Accepted: 01/02/2019] [Indexed: 01/05/2023]
|
|
15
|
Mendes JG, Natour J, Nunes-Tamashiro JC, Toffolo SR, Rosenfeld A, Furtado RNV. Comparison between intra-articular Botulinum toxin type A, corticosteroid, and saline in knee osteoarthritis: a randomized controlled trial. Clin Rehabil 2019; 33:1015-1026. [PMID: 30782000 DOI: 10.1177/0269215519827996] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To compare the effectiveness of intra-articular injection (IAI) with Botulinum toxin type A (BTA), triamcinolone hexacetonide (TH), and saline in primary knee osteoarthritis. DESIGN A randomized controlled trial, with blinded patients and assessor. SETTING Outpatient rheumatology service. SUBJECTS Patients with knee osteoarthritis grades II and III. INTERVENTIONS Patients received IAI with 100 IU BTA, 40 mg TH, or isotonic saline solution (SS) 0.9%. MAIN MEASURES Patients were assessed at baseline and at 4, 8, and 12 weeks with the following instruments: visual analog scale for pain during movement (VASm; primary outcome) and visual analog scale for pain at rest (VASr), Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, 6-minute walk test, Timed Up and Go test, Short Form (SF)-36 questionnaire, range of motion of knee, and ultrasound (US) measurement of synovial hypertrophy. RESULTS In total, 105 patients were randomized, with 35 in each group; 96 were female (91.4%) and 9 were male (8.6%), with a mean age of 64.2 years (±6.9). At 12 weeks, the TH group showed better results only for VASm. At four weeks, the TH group showed better results than the BTA and SS groups for VASm (-68.9% (37.8) vs. -35.3% (40.3) vs. -35.9% (51.4)), WOMAC pain (-56.0% (30.7) vs. -30.8% (34.3) vs. -30.0% (39.9)), WOMAC stiffness (-53.4% (38.4) vs. -17.2% (59.3) vs. -17.3% (78.1)), WOMAC function (-48.2% (34.6) vs. 30.8% (33.6) vs. -13.6% (64.9)), WOMAC total score (-51.2% (31.0) vs. -30.9% (30.0) vs. -18.8% (54.8)), and US measurement of synovial hypertrophy (-11.6% (44.9) vs. -1.5% (47.9) vs. +28.6% (81.3)). CONCLUSION IAI with TH had a higher effectiveness than that with TBA or SS in the short-term assessment (four weeks) for pain in movement, WOMAC, and US measurement of synovial hypertrophy.
Collapse
Affiliation(s)
- Jamille Godoy Mendes
- 1 Rheumatology Division, Escola Paulista de Medicina (UNIFESP-EPM), Universidade Federal de São Paulo, São Paulo, Brazil
| | - Jamil Natour
- 1 Rheumatology Division, Escola Paulista de Medicina (UNIFESP-EPM), Universidade Federal de São Paulo, São Paulo, Brazil
| | - José Carlos Nunes-Tamashiro
- 1 Rheumatology Division, Escola Paulista de Medicina (UNIFESP-EPM), Universidade Federal de São Paulo, São Paulo, Brazil
| | - Sandra Regina Toffolo
- 1 Rheumatology Division, Escola Paulista de Medicina (UNIFESP-EPM), Universidade Federal de São Paulo, São Paulo, Brazil
| | - André Rosenfeld
- 2 Department of Diagnostic Imaging, Escola Paulista de Medicina (UNIFESP-EPM), Universidade Federal de São Paulo, São Paulo, Brazil
| | - Rita Nely Vilar Furtado
- 1 Rheumatology Division, Escola Paulista de Medicina (UNIFESP-EPM), Universidade Federal de São Paulo, São Paulo, Brazil
| |
Collapse
|
|
16
|
McAlindon TE, Schmidt U, Bugarin D, Abrams S, Geib T, DeGryse RE, Kim K, Schnitzer TJ. Efficacy and safety of single-dose onabotulinumtoxinA in the treatment of symptoms of osteoarthritis of the knee: results of a placebo-controlled, double-blind study. Osteoarthritis Cartilage 2018; 26:1291-1299. [PMID: 29753118 DOI: 10.1016/j.joca.2018.05.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 04/13/2018] [Accepted: 05/01/2018] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To evaluate intraarticular onabotulinumtoxinA 400 U and 200 U in reducing symptoms of knee osteoarthritis (OA) in patients with nociceptive pain. DESIGN A multicenter, double-blind, randomized, placebo-controlled study was conducted in adults with knee OA and a painDETECT questionnaire score of ≤12 (indicating nociceptive pain). Patients were randomized to receive intraarticular onabotulinumtoxinA 400 U or 200 U or placebo (saline) in the study knee on a 1:1:2 ratio and were followed-up for 24 weeks posttreatment. The primary efficacy measure was the daily average numeric rating scale pain score for the study knee over 7 days at week 8. Secondary efficacy measures included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function scores, the patient global impression of change score and the 7-day average worst pain score. RESULTS Of the 176 enrolled patients, 158 completed the study. The daily average pain score was reduced by approximately two points for all treatments (week 8); the reduction was sustained throughout follow-up, with no significant between-group difference between onabotulinumtoxinA and placebo (both doses: 0.22 [95% confidence interval (CI): -0.33, 0.76]; 400 U: 0.42 [95% CI: -0.26, 1.10]; 200 U: -0.03 [95% CI: -0.70, 0.64]). Similar results were found for all secondary efficacy measures. Treatment-related adverse events occurred in 3.4% of the pooled onabotulinumtoxinA group and placebo group; none were serious. CONCLUSIONS There were no significant differences between onabotulinumtoxinA and placebo in reducing average pain score at week 8 compared with baseline in patients with knee OA. No safety concerns were identified. CLINICALTRIALS. GOV IDENTIFIER NCT02230956.
Collapse
Affiliation(s)
- T E McAlindon
- Division of Rheumatology, Tufts Medical Center, Boston, MA, USA.
| | - U Schmidt
- CCBR Ballerup, Bioclinica Research Network, Denmark.
| | | | | | - T Geib
- Allergan Plc, Irvine, CA, USA.
| | | | - K Kim
- Allergan Plc, Irvine, CA, USA.
| | - T J Schnitzer
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
| |
Collapse
|
|
17
|
Goldman DT, Piechowiak R, Nissman D, Bagla S, Isaacson A. Current Concepts and Future Directions of Minimally Invasive Treatment for Knee Pain. Curr Rheumatol Rep 2018; 20:54. [PMID: 30033492 DOI: 10.1007/s11926-018-0765-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW The purpose of this paper is to review the percutaneous interventions available for the treatment of osteoarthrosis of the knee that address pain and prolong the time to arthroplasty. RECENT FINDINGS Corticosteroid injection and viscosupplementation have been the most studied, but there is still no consensus about their value. Thermal nerve ablation, including both radiofrequency ablation and cryoneurolysis, is a promising new modality of therapy that may increase in clinical use given current data showing favorable outcomes. Of the future therapies that are currently under investigation, synovial embolization via the geniculate arteries represents an exciting new approach that may soon be available clinically. There are various percutaneous interventions available for the treatment of osteoarthrosis of the knee that address pain and prolong the time to arthroplasty.
Collapse
Affiliation(s)
| | - Rachel Piechowiak
- Vascular & Interventional Radiology, Vascular Institute of Virginia, Woodbridge, Prince William County, VA, USA
| | - Daniel Nissman
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Sandeep Bagla
- Vascular & Interventional Radiology, Vascular Institute of Virginia, Woodbridge, Prince William County, VA, USA
| | - Ari Isaacson
- Vascular and Interventional Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| |
Collapse
|
|
18
|
Cinone N, Letizia S, Santoro L, Gravina M, Amoruso L, Molteni F, Ranieri M, Santamato A. Intra-articular injection of botulinum toxin type A for shoulder pain in glenohumeral osteoarthritis: a case series summary and review of the literature. J Pain Res 2018; 11:1239-1245. [PMID: 29983587 PMCID: PMC6025770 DOI: 10.2147/jpr.s159700] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Shoulder pain is one of the most common musculoskeletal diseases, and can be due to glenohumeral osteoarthritis, rotator cuff tear, impingement, tendinitis, adhesive capsulitis, and subacromial bursitis. Several therapies have been proposed, including steroids, nonsteroidal anti-inflammatory drugs, intra-articular injections, and physical therapies. Many published studies have reported on the employment of botulinum toxin type A (BoNT-A) to reduce pain in subjects with neurological and musculoskeletal diseases by inhibiting substance P release and other inflammatory factors. METHODS In the present article, we briefly update current knowledge regarding intra-articular BoNT therapy, reviewing existing literature on intra-articular use of BoNT-A, including nonrandomized and randomized prospective and retrospective cohort studies and case series published from December 1989 to November 2017. We also describe a case series of six subjects treated with intra-articular injection of incobotulinumtoxin A for the treatment of pain deriving from osteoarthritis. CONCLUSION Intra-articular BoNT-A is effective and minimally invasive. Pain reduction with an increase in shoulder articular range of motion in our experience confirms the effectiveness of BoNT-A injection for the management of this syndrome.
Collapse
Affiliation(s)
- Nicoletta Cinone
- Physical Medicine and Rehabilitation Unit, Ospedali Riuniti, Università di Foggia, Foggia,
| | - Sara Letizia
- Physical Medicine and Rehabilitation Unit, Ospedali Riuniti, Università di Foggia, Foggia,
| | - Luigi Santoro
- Physical Medicine and Rehabilitation Unit, Ospedali Riuniti, Università di Foggia, Foggia,
| | - Michele Gravina
- Rehabilitation Center, "Padre Pio" Foundation, San Giovanni Rotondo
| | - Loredana Amoruso
- Physical Medicine and Rehabilitation Unit, Ospedali Riuniti, Università di Foggia, Foggia,
| | | | - Maurizio Ranieri
- Physical Medicine and Rehabilitation Unit, Ospedali Riuniti, Università di Foggia, Foggia,
| | - Andrea Santamato
- Physical Medicine and Rehabilitation Unit, Ospedali Riuniti, Università di Foggia, Foggia,
- Rehabilitation Center, "Turati" Foundation, Vieste, Italy,
| |
Collapse
|
|
19
|
Alternatives to Biologics in Management of Knee Osteoarthritis: A Systematic Review. Sports Med Arthrosc Rev 2018; 26:79-85. [PMID: 29722769 DOI: 10.1097/jsa.0000000000000190] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Knee osteoarthritis (KOA) is a common condition encountered by physicians. KOA is addressed by a wide array of modalities including a number of nonbiological treatments. METHODS PubMed, ISI Web of Science, and SPORTDiscus were searched for level 1 to 4 studies published from inception to August 2017. RESULTS A total of 18 studies were evaluated and results demonstrated moderate supporting evidence for prolotherapy and limited evidence for botulinum toxin type A, sodium bicarbonate and calcium gluconate, and low-molecular weight fraction of 5% human serum albumin. Evidence for local anesthetic agents was conflicting. CONCLUSION There is moderate supportive evidence for the effectiveness of prolotherapy in improving pain and function in both, short-term and long-term. Limited supporting evidence found for botulinum toxin type A, sodium bicarbonate and calcium gluconate, and low-molecular weight fraction of 5% human serum albumin in improving pain and function. There is conflicting evidence for the use of local anesthetic agents in patients with KOA.
Collapse
|
|
20
|
Shukla D, Sreedhar SK, Rastogi V. A Comparative Study of Botulinum Toxin: A with Triamcinolone Compared to Triamcinolone alone in the treatment of Osteoarthritis of Knee. Anesth Essays Res 2018; 12:47-49. [PMID: 29628553 PMCID: PMC5872892 DOI: 10.4103/aer.aer_210_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Introduction: This study compares the efficacy in terms of pain relief and complications of intra-articular Botulinum toxin-A (BoNT-A) with intra-articular Triamcinolone versus Triamcinolone alone in the treatment of osteoarthritic knee pain of severe grade. If effective, BoNT-A may help in reducing the long term adverse effects due to prolonged analgesic consumption and reduce/delay requirement of knee replacement surgeries. Materials and Methods: In this prospective study, 30 patients of either sex, aged between 40 to 60 years with physical status ASA classes I or II suffering from knee joint osteoarthritis with knee pain and functional impairment were divided into 2 groups: The OA patients which received Botulinum toxin-A with Triamcinolone (Group A) & OA patients which received only Triamcinolone (Group B). Only patients with advanced OA of the knee; radiographically verified with a Joint space <2 mm were included. The efficacy of pain relief in the 2 groups were compared using Visual analog score (VAS) and Oxford knee Score and followed upto 6 months. Results and Conclusions: On comparing the VAS Score during the follow up period, there was a significant difference between groups A and B upto 3 months. During post treatment follow up, there was significant difference in pain relief as measured by the Oxford Knee score from 4 weeks to 6 months, where Group A patients fared much better in terms of pain relief than group B with a highly significant value of P =<0.001 during the time period of 6 weeks to 6 months. The study shows that the use intra-articular Botulinum toxin-A with steroid is far superior to intra-articular steroid alone in terms of pain relief as well as functional outcome.
Collapse
Affiliation(s)
- Divya Shukla
- Department of Anesthesiology, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India
| | - Smitha K Sreedhar
- Department of Anesthesiology, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India
| | - Virendra Rastogi
- Department of Anesthesiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| |
Collapse
|
|
21
|
Calvet J, Orellana C, Galisteo C, García-Manrique M, Navarro N, Caixàs A, Larrosa M, Gratacós J. Clinical and ultrasonographic features associated to response to intraarticular corticosteroid injection. A one year follow up prospective cohort study in knee osteoarthritis patient with joint effusion. PLoS One 2018; 13:e0191342. [PMID: 29351562 PMCID: PMC5774783 DOI: 10.1371/journal.pone.0191342] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 01/03/2018] [Indexed: 01/29/2023] Open
Abstract
OBJECTIVES Intraarticular injection is used for pain relief in knee osteoarthritis (OA), but there is not a well defined profile of patient who could get more benefit from it. The purpose of this study was to evaluate the frequency of pain relief at one year after corticosteroids intraarticular injection and to identify clinical factors associated to response in patients with knee osteoarthritis with joint effusion. METHODS One-year prospective cohort study of patients with knee OA with joint effusion confirmed by ultrasound. An intraarticular injection was performed following a clinical protocol. Anthropometric measurements, laboratory parameters, clinical severity, ultrasound parameters and radiological severity were collected. Response regarding pain and presence of synovial fluid on ultrasound at one month and at one year were evaluated. Clinical responder were consider in subjects with enough improvement to carry out normal daily activities with pain VAS<40mm. RESULTS One hundred and thirty-two patients were included.A significant number of patients (61.4%) improved pain at one year following the protocol established in this study. Pain and ultrasound synovial fluid at one month appeared to predict the response at one year. The Lequesne index and the percentage of body fat were independently associated to pain at one year while the Lequesne index and ultrasound synovial hypertrophy were independently related to the presence of synovial fluid at one year. CONCLUSIONS The status regarding pain or ultrasound synovial fluid at one month after an intraarticular joint injection appeared to predict the status at one year in patients with knee osteoarthritis and synovial effusion.
Collapse
Affiliation(s)
- Joan Calvet
- Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| | - Cristóbal Orellana
- Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| | - Carlos Galisteo
- Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| | - María García-Manrique
- Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| | - Noemí Navarro
- Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| | - Assumpta Caixàs
- Endocrinology and Nutrition Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| | - Marta Larrosa
- Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| | - Jordi Gratacós
- Rheumatology Department, Parc Taulí Sabadell University Hospital. I3PT Research Institute (UAB), Sabadell, Barcelona, Spain
| |
Collapse
|
|
22
|
Heikkilä HM, Jokinen TS, Syrjä P, Junnila J, Hielm-Björkman A, Laitinen-Vapaavuori O. Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial. PLoS One 2018; 13:e0191043. [PMID: 29320549 PMCID: PMC5761897 DOI: 10.1371/journal.pone.0191043] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 12/27/2017] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. METHODS A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. RESULTS Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. CONCLUSION Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.
Collapse
Affiliation(s)
- Helka M. Heikkilä
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
- * E-mail:
| | - Tarja S. Jokinen
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Pernilla Syrjä
- Department of Veterinary Biosciences, Veterinary Pathology, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | | | - Anna Hielm-Björkman
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Outi Laitinen-Vapaavuori
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| |
Collapse
|
|
23
|
Nguyen C, Rannou F. The safety of intra-articular injections for the treatment of knee osteoarthritis: a critical narrative review. Expert Opin Drug Saf 2017. [PMID: 28627937 DOI: 10.1080/14740338.2017.1344211] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION International guidelines recommend that the management of knee osteoarthritis (OA) combine both nonpharmacological and pharmacological interventions. Intra-articular (IA) therapies are considered part of this multimodal approach and are well-established Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved treatments. Areas covered: Safety data for knee OA, including IA corticosteroids, hyaluronic acid, platelet-rich plasma and botulinum toxin are critically reviewed, and evidence- and pratice-based measures to improve safety of IA therapies are discussed. Expert opinion: The incidence of AEs attributable to IA therapies across clinical trials in knee OA is very low, and barely reaches significance when compared to the incidence of AEs in the comparator group. These events are exceptionally serious. Mild differences between products have been inconsistently reported mainly for IA HA. One can distinguish self-limited AEs such as post-injection pain and swelling that are the most frequently reported AEs, from AEs that are not self-limited but rare such as septic arthritis. The safety of IA therapies can be improved by applying simple measures designed to prevent AEs. However, even though no specific safety concerns have been raised to date about IA therapies, the quality of evidence is low, and there is a need to improve the monitoring and reporting of safety data from clinical trials and post-marketing surveillance.
Collapse
Affiliation(s)
- Christelle Nguyen
- a Université Paris Descartes, Faculté de Médecine , Paris , France.,b INSERM UMR 1124, Faculté des Sciences Fondamentales et Biomédicales , Paris , France.,c AP-HP, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpitaux Universitaires Paris Centre Paris - Groupe Hospitalier Cochin , Paris , France
| | - François Rannou
- a Université Paris Descartes, Faculté de Médecine , Paris , France.,b INSERM UMR 1124, Faculté des Sciences Fondamentales et Biomédicales , Paris , France.,c AP-HP, Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpitaux Universitaires Paris Centre Paris - Groupe Hospitalier Cochin , Paris , France
| |
Collapse
|
|
24
|
The effect of intra-articular botulinum toxin A on substance P, prostaglandin E 2, and tumor necrosis factor alpha in the canine osteoarthritic joint. BMC Vet Res 2017; 13:74. [PMID: 28327134 PMCID: PMC5359943 DOI: 10.1186/s12917-017-0990-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 03/08/2017] [Indexed: 11/27/2022] Open
Abstract
Background Recently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α) in osteoarthritic dogs. Additionally, the aim was to compare SF SP and PGE2 between osteoarthritic and non-osteoarthritic joints, and investigate associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs. Thirty-five dogs with chronic naturally occurring osteoarthritis and 13 non-osteoarthritic control dogs were included in the study. Osteoarthritic dogs received either IA BoNT A (n = 19) or IA placebo (n = 16). Serum and SF samples were collected and osteoarthritic pain was evaluated before (baseline) and 2 and 8 weeks after treatment. Osteoarthritic pain was assessed with force platform, Helsinki Chronic Pain Index, and joint palpation. Synovial fluid samples were obtained from control dogs after euthanasia. The change from baseline in SP and PGE2 concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE2 concentration was compared between osteoarthritic and control joints. Associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs were evaluated. Results There was no significant change from baseline in SP or PGE2 after IA BoNT A. Synovial fluid PGE2 was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE2 correlated with osteoarthritic pain. No associations were found between SP or PGE2 and the signalment of dogs. The concentration of TNF-α remained under the detection limit of the assay in all samples. Conclusions The results suggest that the antinociceptive effect of IA BoNT A in the joint might not be related to the inhibition of SP nor PGE2. Synovial fluid PGE2, but not SP, could be a marker for chronic osteoarthritis and pain in dogs.
Collapse
|
|
25
|
Arendt-Nielsen L, Jiang GL, DeGryse R, Turkel CC. Intra-articular onabotulinumtoxinA in osteoarthritis knee pain: effect on human mechanistic pain biomarkers and clinical pain. Scand J Rheumatol 2016; 46:303-316. [PMID: 27733091 DOI: 10.1080/03009742.2016.1203988] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES OnabotulinumtoxinA (onabotA) attenuates peripheral nociceptive transduction and consequently neuronal firing. The aim of this mechanistic study was to evaluate the effect of intra-articular (IA) onabotA in patients with painful knee osteoarthritis (OA). METHOD We conducted a double-blind, randomized, placebo-controlled, 12-week trial using a single ultrasound-guided IA injection of onabotA (200 U). Patients (N = 121) were randomized to receive onabotA (n = 61) or placebo (n = 60). Mechanistic pain biomarkers and clinical outcomes were used for profiling the effect. The biomarkers were pressure pain thresholds (PPTs) from the knee joint (localized sensitization) and extra-articular sites (widespread sensitization), and wind-up pain (central sensitization). Clinical assessments included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), average daily pain (ADP), patient global impression of change (GIC), and rescue medication. The painDETECT questionnaire (PD-Q) was used for subgrouping patients (nociceptive, neuropathic, and mixed/uncertain). RESULTS The nociceptive and non-nociceptive groups were identical with respect to all baseline data. No significant differences in clinical efficacy parameters were found between onabotA and placebo in the entire population. The nociceptive group showed significant improvement after IA onabotA at week 8 for all WOMAC outcomes, ADP at weeks 9 and 10, and patient GIC at week 12, and significant reduction in rescue medication counts within each 14-day period at weeks 9 and 10. After 4, 8, and 12 weeks, significant correlations were obtained in the onabotA group between ADP (both the entire group and the nociceptive group) and various sensitization parameters. The nociceptive group showed pronounced effects on widespread sensitization. CONCLUSIONS Intra-articular onabotA given to patients with nociceptive knee OA reduced pain sensitization together with improvement in pain and function.
Collapse
Affiliation(s)
| | - G-L Jiang
- b Sanofi Biosurgery DPU , Cambridge , MA , USA
| | - R DeGryse
- c Allergan, Inc. , Irvine , CA , USA
| | | |
Collapse
|
|
26
|
|
|
27
|
Wu T, Song HX, Dong Y, Ye Y, Li JH. Intra-articular injections of botulinum toxin a for refractory joint pain: a systematic review and meta-analysis. Clin Rehabil 2016; 31:435-443. [PMID: 27094033 DOI: 10.1177/0269215516644951] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Tao Wu
- Department of Rehabilitation Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hang Zhou, PR China
- Tao Wu and Hai-xin Song contributed equally to this work
| | - Hai-xin Song
- Department of Rehabilitation Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hang Zhou, PR China
- Tao Wu and Hai-xin Song contributed equally to this work
| | - Yan Dong
- Department of Rehabilitation Medicine, Hangzhou Hospital of Zhejiang CAPF, Hang Zhou, PR China
| | - Ye Ye
- Department of Rehabilitation Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hang Zhou, PR China
| | - Jian-hua Li
- Department of Rehabilitation Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hang Zhou, PR China
| |
Collapse
|
|
28
|
van Middelkoop M, Arden NK, Atchia I, Birrell F, Chao J, Rezende MU, Lambert RGW, Ravaud P, Bijlsma JW, Doherty M, Dziedzic KS, Lohmander LS, McAlindon TE, Zhang W, Bierma-Zeinstra SMA. The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids. Osteoarthritis Cartilage 2016; 24:1143-52. [PMID: 26836288 DOI: 10.1016/j.joca.2016.01.983] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 11/26/2015] [Accepted: 01/22/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. DESIGN Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (≥70 points, 0-100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study. RESULTS Seven out of 43 published randomized clinical trials (n = 620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid- and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% Confidence Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. CONCLUSIONS This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline.
Collapse
Affiliation(s)
- M van Middelkoop
- Erasmus MC Medical University Center Rotterdam, Department of General Practice, The Netherlands.
| | - N K Arden
- Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, OX3 7LD, UK; Arthritis Research UK Centre of Excellence for Sports, Exercise and Osteoarthritis, University of Oxford, OX3 7LD, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton SO16 6YD, UK.
| | - I Atchia
- Northumbria Healthcare NHS Foundation Trust, University of Newcastle, UK.
| | - F Birrell
- Northumbria Healthcare NHS Foundation Trust, University of Newcastle, UK.
| | - J Chao
- UCSD School of Medicine, La Jolla, CA, USA.
| | - M U Rezende
- Instituto de Ortopedia e Traumatologia, Faculdade de Medicina, HCFMUSP, Sao Paulo, Brazil.
| | - R G W Lambert
- Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton, Canada.
| | - P Ravaud
- Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité, Paris, France.
| | - J W Bijlsma
- University Medical Center Utrecht, Department of Rheumatology & Clinical Immunology, Utrecht, The Netherlands.
| | - M Doherty
- Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK.
| | - K S Dziedzic
- Arthritis Research UK Primary Care Centre, Primary Care Sciences, Keele University, UK.
| | - L S Lohmander
- Lund University, Department of Orthopaedics, Clinical Sciences Lund, Sweden; Institute of Sports Science and Clinical Biomechanics, Department of Orthopaedics and Traumatology, University of Southern Denmark, Denmark.
| | - T E McAlindon
- Tufts University, Department of Medicine, Boston, USA.
| | - W Zhang
- Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK.
| | - S M A Bierma-Zeinstra
- Erasmus MC Medical University Center Rotterdam, Department of General Practice, The Netherlands.
| |
Collapse
|
|
29
|
Nguyen C, Lefèvre-Colau MM, Poiraudeau S, Rannou F. Evidence and recommendations for use of intra-articular injections for knee osteoarthritis. Ann Phys Rehabil Med 2016; 59:184-189. [DOI: 10.1016/j.rehab.2016.02.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2015] [Revised: 02/22/2016] [Accepted: 02/28/2016] [Indexed: 12/13/2022]
|
|
30
|
Hsieh LF, Wu CW, Chou CC, Yang SW, Wu SH, Lin YJ, Hsu WC. Effects of Botulinum Toxin Landmark-Guided Intra-articular Injection in Subjects With Knee Osteoarthritis. PM R 2016; 8:1127-1135. [PMID: 27210235 DOI: 10.1016/j.pmrj.2016.05.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Revised: 05/02/2016] [Accepted: 05/08/2016] [Indexed: 01/22/2023]
Abstract
BACKGROUND Increasing evidence has suggested that botulinum toxin A (BoNT/A) can inhibit the release of selected neuropeptide transmitters from primary sensory neurons. Thus, intra-articular (IA) injection therapies with BoNT/A may reduce pain in patients with knee osteoarthritis (OA). OBJECTIVE To investigate the effects of landmark-guided IA injection of BoNT/A on patients with knee OA. DESIGN A prospective randomized controlled trial. SETTING A rehabilitation clinic of a private teaching hospital. PATIENTS A total of 46 patients with symptomatic knee OA (mostly Kellgren-Lawrence grade 2-3). METHODS The patients were randomly assigned to 1 of the following groups: BoNT/A group (BoNT/A injection; n = 21) or control group (education only; n = 20). The patients in the BoNT/A group received an IA injection of 100 units of BoNT/A into the affected knee. MAIN OUTCOME MEASURES The short-term (1 week posttreatment) and long-term (6 months posttreatment) effects were evaluated using a pain visual analogue scale (VAS) and questionnaires concerning functional status, including the Lequesne and Western Ontario and McMaster Universities (WOMAC) indexes. RESULTS The between-group comparison revealed significant differences with regard to the pain VAS score at 1 week (P < .001) and at 6 months (P = .001) posttreatment. Similar findings for the between-group comparison were observed for the WOMAC and Lequesne indexes at 6 months (P < .05) posttreatment. The pain VAS score in the BoNT/A group significantly decreased from 5.05 ± 1.12 (pretreatment) to 2.89 ± 1.04 at 1 week (P < .001) and 3.45 ± 1.70 at 6 months posttreatment (P < .001) but not in the control group (P = .476). CONCLUSIONS The IA injection of BoNT/A provided pain relief and improved functional abilities in patients with knee OA in both the short- and long-term follow-up. LEVEL OF EVIDENCE I.
Collapse
Affiliation(s)
- Lin-Fen Hsieh
- Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, Republic of China(∗)
| | - Chia-Wei Wu
- Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China(†)
| | - Ching-Chieh Chou
- Neuromuscular Research Laboratory, Department of Physical Therapy, Chang Gung University, Tao-Yuan, Taiwan, Republic of China(‡)
| | - Sai-Wei Yang
- Department of Biomedical Engineering, National Yang-Ming University, No. 155, Section 2, Li-Nong Street, Taipei, Taiwan, Republic of China(§).
| | - Shih-Hui Wu
- Department of Physical Medicine and Rehabilitation, Cardinal Tien Hospital, Taipei, Taiwan, Republic of China(‖)
| | - Yi-Jia Lin
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, Republic of China(¶)
| | - Wei-Chun Hsu
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, Republic of China; National Defense Medical Center, Taipei, Taiwan, Republic of China(#)
| |
Collapse
|
|
31
|
Richards MM, Maxwell JS, Weng L, Angelos MG, Golzarian J. Intra-articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. PHYSICIAN SPORTSMED 2016; 44:101-8. [PMID: 26985986 PMCID: PMC4932822 DOI: 10.1080/00913847.2016.1168272] [Citation(s) in RCA: 114] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVES Knee osteoarthritis (OA) is a debilitating condition that may ultimately require total knee arthroplasty (TKA). Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI). The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment. METHODS A literature search was executed using Medline, Cochrane, and Embase with keywords "knee osteoarthritis" and "injection." Specifically, 45 articles that discussed intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSC), were analyzed. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5 evidence. Papers included animal models. RESULTS Local anesthetics have potential side effects and may only be effective for a few hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation . Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint. CONCLUSIONS Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they may ultimately have profound implications in the way knee OA is managed.
Collapse
Affiliation(s)
- Masters M. Richards
- University of Minnesota-School of Medicine, Department of Vascular and Interventional Radiology 420 Delaware St. SE, Minneapolis, MN 55455, Ph. (612)626-5388
| | - Joshua Shane Maxwell
- University of Minnesota-School of Medicine, Department of Family Medicine and Community Health, 420 Delaware St. SE, MMC 381, Minneapolis, MN 55455, Ph. (612)625-0646
| | - Lihui Weng
- University of Minnesota-School of Medicine, Department of Vascular and Interventional Radiology 420 Delaware St. SE, Minneapolis, MN 55455, Ph. (612)626-5388
| | - Mathew G. Angelos
- University of Minnesota-School of Medicine, Department of Hematology, Oncology, and Transplantation, 401 East River Parkway, Suite 131, MMC 194, Minneapolis, Minnesota 55455, Ph. (612)625-3654
| | - Jafar Golzarian
- University of Minnesota-School of Medicine, Department of Vascular and Interventional Radiology 420 Delaware St. SE, Minneapolis, MN 55455, Ph. (612)626-5388
| |
Collapse
|
|
32
|
Khenioui H, Houvenagel E, Catanzariti JF, Guyot MA, Agnani O, Donze C. Usefulness of intra-articular botulinum toxin injections. A systematic review. Joint Bone Spine 2015; 83:149-54. [PMID: 26645160 DOI: 10.1016/j.jbspin.2015.10.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2015] [Indexed: 10/22/2022]
Abstract
UNLABELLED Botulinum toxin is a proven and widely used treatment for numerous conditions characterized by excessive muscular contractions. Recent studies have assessed the analgesic effect of botulinum toxin in joint pain and started to unravel its mechanisms. LITERATURE-SEARCH-METHODOLOGY We searched the international literature via the Medline database using the term "intraarticular botulinum toxin injection" combined with any of the following terms: "knee", "ankle", "shoulder", "osteoarthritis", "adhesive capsulitis of the shoulder". RESULTS Of 16 selected articles about intraarticular botulinum toxin injections, 7 were randomized controlled trials done in patients with osteoarthritis, adhesive capsulitis of the shoulder, or chronic pain after joint replacement surgery. Proof of anti-nociceptive effects was obtained in some of these indications and the safety and tolerance profile was satisfactory. The studies are heterogeneous. The comparator was usually a glucocorticoid or a placebo; a single study used hyaluronic acid. Pain intensity was the primary outcome measure. DISCUSSION-CONCLUSION The number of randomized trials and sample sizes are too small to provide a satisfactory level of scientific evidence or statistical power. Unanswered issues include the effective dosage and the optimal dilution and injection modalities of botulinum toxin.
Collapse
Affiliation(s)
- Hichem Khenioui
- Service de médecine physique et de réadaptation, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France; Université Nord de France, 1, rue Lefèvre, 59000 Lille, France; Université catholique de Lille, 60, boulevard Vauban, 59800 Lille, France.
| | - Eric Houvenagel
- Université Nord de France, 1, rue Lefèvre, 59000 Lille, France; Université catholique de Lille, 60, boulevard Vauban, 59800 Lille, France; Service de rhumatologie, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France
| | - Jean François Catanzariti
- Service de médecine physique et de réadaptation, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France; Université Nord de France, 1, rue Lefèvre, 59000 Lille, France; Service de rhumatologie, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France; Service de médecine physique et réadaptation, centre de SSR pédiatrique Marc-Sautelet, 10, rue du Petit-Boulevard, 59650 Villeneuve-d'Ascq, France
| | - Marc Alexandre Guyot
- Service de médecine physique et de réadaptation, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France; Université Nord de France, 1, rue Lefèvre, 59000 Lille, France; Service de rhumatologie, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France
| | - Olivier Agnani
- Service de médecine physique et de réadaptation, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France; Université Nord de France, 1, rue Lefèvre, 59000 Lille, France; Service de rhumatologie, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France
| | - Cécile Donze
- Service de médecine physique et de réadaptation, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France; Université Nord de France, 1, rue Lefèvre, 59000 Lille, France; Service de rhumatologie, centre hospitalier Saint-Philibert, groupe hospitalier de l'institut catholique de Lille, 115, rue du Grand-But, BP 249, 59462 Lomme cedex, France
| |
Collapse
|
|
33
|
Current status and future directions of botulinum neurotoxins for targeting pain processing. Toxins (Basel) 2015; 7:4519-63. [PMID: 26556371 PMCID: PMC4663519 DOI: 10.3390/toxins7114519] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 09/29/2015] [Accepted: 10/19/2015] [Indexed: 12/20/2022] Open
Abstract
Current evidence suggests that botulinum neurotoxins (BoNTs) A1 and B1, given locally into peripheral tissues such as skin, muscles, and joints, alter nociceptive processing otherwise initiated by inflammation or nerve injury in animal models and humans. Recent data indicate that such locally delivered BoNTs exert not only local action on sensory afferent terminals but undergo transport to central afferent cell bodies (dorsal root ganglia) and spinal dorsal horn terminals, where they cleave SNAREs and block transmitter release. Increasing evidence supports the possibility of a trans-synaptic movement to alter postsynaptic function in neuronal and possibly non-neuronal (glial) cells. The vast majority of these studies have been conducted on BoNT/A1 and BoNT/B1, the only two pharmaceutically developed variants. However, now over 40 different subtypes of botulinum neurotoxins (BoNTs) have been identified. By combining our existing and rapidly growing understanding of BoNT/A1 and /B1 in altering nociceptive processing with explorations of the specific characteristics of the various toxins from this family, we may be able to discover or design novel, effective, and long-lasting pain therapeutics. This review will focus on our current understanding of the molecular mechanisms whereby BoNTs alter pain processing, and future directions in the development of these agents as pain therapeutics.
Collapse
|
|
34
|
Fibel KH, Hillstrom HJ, Halpern BC. State-of-the-Art management of knee osteoarthritis. World J Clin Cases 2015; 3:89-101. [PMID: 25685755 PMCID: PMC4317618 DOI: 10.12998/wjcc.v3.i2.89] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Revised: 09/29/2014] [Accepted: 10/28/2014] [Indexed: 02/05/2023] Open
Abstract
Osteoarthritis (OA) is the most common type of arthritis found in the United States' population and is also the most common disease of joints in adults throughout the world with the knee being the most frequently affected of all joints. As the United States' population ages along with the increasing trends in obesity prevalence in other parts of the world, it is expected that the burden of OA on the population, healthcare system, and overall economy will continue to increase in the future without making major improvements in managing knee OA. Numerous therapies aim to reduce symptoms of knee OA and continued research has helped to further understand the complex pathophysiology of its disease mechanism attempting to uncover new potential targets for the treatment of OA. This review article seeks to evaluate the current practices for managing knee OA and discusses emerging therapies on the horizon. These practices include non-pharmacological treatments such as providing patient education and self-management strategies, advising weight loss, strengthening programs, and addressing biomechanical issues with bracing or foot orthoses. Oral analgesics and anti-inflammatories are pharmacologicals that are commonly used and the literature overall supports that some of these medications can be helpful for managing knee OA in the short-term but are less effective for long-term management. Additionally, more prolonged use significantly increases the risk of serious associated side effects that are not too uncommon. Disease-modifying osteoarthritis drugs are being researched as a treatment modality to potentially halt or slow disease progression but data at this time is limited and continued studies are being conducted to further investigate their effectiveness. Intra-articular injectables are also implemented to manage knee OA ranging from corticosteroids to hyaluronans to more recently platelet-rich plasma and even stem cells while several other injection therapies are presently being studied. The goal of developing new treatment strategies for knee OA is to prolong the need for total knee arthroplasty which should be utilized only if other strategies have failed. High tibial osteotomy and unicompartmental knee arthroplasty are potential alternatives if only a single compartment is involved with more data supporting unicompartmental knee arthroplasty as a good treatment option in this scenario. Arthroscopy has been commonly used for many years to treat knee OA to address degenerative articular cartilage and menisci, however, several high-quality studies have shown that it is not a very effective treatment for the majority of cases and should generally not be considered when managing knee OA. Improving the management of knee OA requires a multi-faceted treatment approach along with continuing to broaden our understanding of this complex disease so that therapeutic advancements can continue to be developed with the goal of preventing further disease progression and even potentially reversing the degenerative process.
Collapse
|
|
35
|
Vázquez-Portalatín N, Breur GJ, Panitch A, Goergen CJ. Accuracy of ultrasound-guided intra-articular injections in guinea pig knees. Bone Joint Res 2015; 4:1-5. [PMID: 25588586 PMCID: PMC4309960 DOI: 10.1302/2046-3758.41.2000370] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint. METHODS A high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. A total of 36 guinea pigs were anaesthetised with isoflurane and placed on a heated stage. Sterile needles were inserted directly into the knee joint medially, while the transducer was placed on the lateral surface, allowing the femur, tibia and fat pad to be visualised in the images. B-mode cine loops were acquired during 100 µl. We assessed our ability to visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical changes due to the injection. RESULTS From the ultrasound images, we were able to visualise clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. We also observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a smaller subset of injections. CONCLUSION The results demonstrate that this image-guided technique can be used to visualise the location of an intra-articular injection in the joints of guinea pigs. Future studies using an ultrasound-guided approach could help improve the injection accuracy in a variety of anatomical locations and animal models, in the hope of developing anti-arthritic therapies. Cite this article: Bone Joint Res 2015;4:1-5.
Collapse
Affiliation(s)
| | - G J Breur
- Purdue University, West Lafayette, Indiana 47907, USA
| | - A Panitch
- Purdue University, West Lafayette, Indiana 47907, USA
| | - C J Goergen
- Purdue University, West Lafayette, Indiana 47907, USA
| |
Collapse
|
|
36
|
Heikkilä HM, Hielm-Björkman AK, Morelius M, Larsen S, Honkavaara J, Innes JF, Laitinen-Vapaavuori OM. Intra-articular botulinum toxin A for the treatment of osteoarthritic joint pain in dogs: a randomized, double-blinded, placebo-controlled clinical trial. Vet J 2014; 200:162-9. [PMID: 24675370 DOI: 10.1016/j.tvjl.2014.01.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Revised: 01/27/2014] [Accepted: 01/29/2014] [Indexed: 01/09/2023]
Abstract
The aim of this study was to investigate the efficacy of intra-articular (IA) botulinum toxin A (IA BoNT A) for the treatment of osteoarthritic joint pain in dogs. The study was a placebo-controlled, randomized, double-blinded clinical trial with parallel group design and 12-week follow-up. Thirty-six dogs with chronic lameness due to stifle, hip or elbow osteoarthritis were randomized to receive an IA injection of 30IU of BoNT A or placebo. The main outcome variables were vertical impulse (VI) and peak vertical force (PVF) measured with a force platform, and Helsinki chronic pain index (HCPI). Subjective pain score and the need for rescue analgesics were secondary variables. The response to treatment was assessed as the change from baseline to each examination week. The variables were analyzed by ANOVA with repeated measurements and results were considered statistically significant if P ⩽ 0.05. The improvement from baseline to 12 weeks after baseline was statistically significant in VI, PVF and HCPI in the treatment group (P=0.001, P=0.054 and P=0.053, respectively). Additionally, there were statistically significant improvements in VI in the treatment group at 2, 4 and 8 weeks after baseline (P=0.037, P=0.016 and P=0.016, respectively). The difference between groups in improvement in VI was statistically significant at 12weeks after baseline (P=0.005). There was no significant change in the subjective pain score or in the requirement for rescue analgesics in either group. No major adverse events thought to be related to trial protocol were detected. These results suggest that IA BoNT A has some efficacy in reducing osteoarthritic pain in dogs.
Collapse
Affiliation(s)
- H M Heikkilä
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, P.O. Box 57, 00014 University of Helsinki, Finland.
| | - A K Hielm-Björkman
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, P.O. Box 57, 00014 University of Helsinki, Finland
| | - M Morelius
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, P.O. Box 57, 00014 University of Helsinki, Finland
| | - S Larsen
- Centre for Epidemiology and Biostatistics, Norwegian School of Veterinary Science, P.O. Box 8146 Dep, 0033 Oslo, Norway
| | - J Honkavaara
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, P.O. Box 57, 00014 University of Helsinki, Finland
| | - J F Innes
- Department of Musculoskeletal Biology, Institute of Aging and Chronic Disease and School of Veterinary Science, University of Liverpool, Chester High Road, Neston CH64 7TE, UK
| | - O M Laitinen-Vapaavuori
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, P.O. Box 57, 00014 University of Helsinki, Finland
| |
Collapse
|
|
37
|
Huleatt JB, Campbell KJ, Laprade RF. Nonoperative treatment approach to knee osteoarthritis in the master athlete. Sports Health 2014; 6:56-62. [PMID: 24427443 PMCID: PMC3874223 DOI: 10.1177/1941738113501460] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Context: Middle-age and elderly participants in athletic activities frequently encounter the chronic disabling process of osteoarthritis. Knowledge of the treatment of knee osteoarthritis is needed to keep the master athlete active. Objective: This article reviews the current scientific evidence regarding recommendations for the maturing athlete, specifically discussing the strengths and weaknesses of dietary and lifestyle modifications, physical therapy, bracing, supplements, pharmacotherapies, and biologics in the management of knee osteoarthritis. Level of Evidence: Level 4. Conclusion: These treatment modalities can help keep the aging athlete active, which in itself plays an important role in reducing the symptoms of knee osteoarthritis.
Collapse
|
|
38
|
Singh JA. Efficacy of Long-term Effect and Repeat Intraarticular Botulinum toxin in Patients with Painful Total Joint Arthroplasty: A Retrospective Study. ACTA ACUST UNITED AC 2014; 4. [PMID: 24319672 PMCID: PMC3850174 DOI: 10.9734/bjmmr/2014/4897] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Objective Based on recent success of intra-articular (IA) Botulinum neurotoxin type A (BoNT/A; OnabotulinumtoxinA) in patients with osteoarthritis, we examined if repeat IA-BoNT/A is an effective antinociceptive in patients with refractory arthroplasty pain. Methods 11 patients with refractory chronic arthroplasty joint pain without any evidence of infection or prosthesis loosening were referred by orthopedic surgeons. After discussion of off-label use, each patient underwent IA injection of BoNT/A, repeated based on return of pain on numeric rating scale (NRS) and functional limitation on composite validated scales, Western Ontario McMaster Osteoarthritis index (WOMAC) or Shoulder Pain and Disability (SPADI). Results 11 patients (10 men, 1 woman) with 14 painful arthroplasty joints (3 bilateral; 12 knee and 2 shoulder) underwent ≥1 IA-BoNT/A injections (8 joints injected once, one joint injected twice only, five joints injected thrice) with doses ranging 100–300 units. Mean age was 68 years (standard deviation, 12) and follow-up ranged 1–28 months. Clinically meaningful reduction of 2-units in pain severity and really meaningful reduction in pain severity (50% reduction) were reported by 6/11 patients (6/13 joints) and 3/11 patients (3/13 joints), respectively, 1 month after the first IA-BoNT/A (100-units each). Significant improvements were noted in composite functional scales (WOMAC/SPADI). Pain relief was sustained at 3–4 month follow-up and was reproducible in those who received repeat injections. No significant adverse events were seen in any patients. Conclusions A single intra-articular injection of BoNT/A improved pain and function in patients with chronic, refractory painful knee or shoulder arthroplasty, which sustained with repeat injections. Patients who were refractory to the first injection, did not respond to subsequent injections of higher dose of IA-BoNT/A.
Collapse
Affiliation(s)
- Jasvinder A Singh
- Medicine Service and Center for Surgical Medical Acute Care Research and Transitions (C-SMART), Birmingham VA Medical Center, Birmingham, AL; USA ; Department of Medicine, University of Alabama, and Division of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL; USA. ; Department of Orthopedic Surgery, Mayo Clinic School of Medicine, Rochester, MN, USA
| |
Collapse
|
|
39
|
Abstract
Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the treatment of a wide range of arthropathies. Possible benefits over systemic delivery include increased bioavailability, reduced systemic exposure, fewer adverse events, and lower total drug costs. Nevertheless, intra-articular therapy is challenging because of the rapid egress of injected materials from the joint space; this elimination is true of both small molecules, which exit via synovial capillaries, and of macromolecules, which are cleared by the lymphatic system. In general, soluble materials have an intra-articular dwell time measured only in hours. Corticosteroids and hyaluronate preparations constitute the mainstay of FDA-approved intra-articular therapeutics. Recombinant proteins, autologous blood products and analgesics have also found clinical use via intra-articular delivery. Several alternative approaches, such as local delivery of cell and gene therapy, as well as the use of microparticles, liposomes, and modified drugs, are in various stages of preclinical development.
Collapse
Affiliation(s)
- Christopher H Evans
- Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN-115, Boston, MA 02215, USA
| | - Virginia B Kraus
- Duke University Medical Center, Department of Medicine, Box 3416, Durham, NC 27710, USA
| | - Lori A Setton
- Department of Biomedical Engineering, Duke University, Room 136 Hudson Hall, Box 90281, Durham, NC 27708, USA
| |
Collapse
|
|
40
|
Anti-inflammatory effects of botulinum toxin type a in a complete Freund's adjuvant-induced arthritic knee joint of hind leg on rat model. Neurotox Res 2013; 26:32-9. [PMID: 24338136 DOI: 10.1007/s12640-013-9447-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2013] [Revised: 11/25/2013] [Accepted: 11/28/2013] [Indexed: 02/02/2023]
Abstract
The objective of the study is to verify histopathologically the anti-inflammatory effect of botulinum toxin type A (BoNT-A) in a Complete Freund's Adjuvant (CFA)-induced arthritic knee joint of hind leg on rat model using immunofluorescent staining of anti-ionized calcium-binding adaptor molecule 1 (Iba-1) and interleukin-1β (IL-1β) antibody. Twenty-eight experimental rats were injected with 0.1 ml of CFA solution in the knee joint of the hind leg bilaterally. Three weeks after CFA injection, the BoNT-A group (N = 14) was injected with 20 IU (0.1 ml) of BoNT-A bilaterally while the saline group (N = 14) was injected with 0.1 ml of saline in the knee joint of the hind leg bilaterally. One and two weeks after BoNT-A or saline injection, joint inflammation was investigated in seven rats from each group using histopathological and immune-fluorescent staining of Iba-1 and IL-1β antibody. The number of Iba-1 and IL-1β immune-reactive (IR) cells was counted in the BoNT-A and saline groups for comparison. There was a significant reduction in joint inflammation and destruction in the BoNT-A group at 1 and 2 weeks after BoNT-A injection compared with the saline group. The binding of Iba-1 and IL-1β antibody was significantly lower in the BoNT-A group than the saline group at 1 and 2 weeks after BoNT-A injection. The number of Iba-1 and IL-1β-IR cells at 1 and 2 weeks after the injection of BoNT-A were significantly different from the corresponding number of Iba-1 and IL-1β-IR cells in the saline group. To conclude, BoNT-A had an anti-inflammatory effect in a CFA-induced arthritic rat model, indicating that BoNT-A could potentially be used to treat inflammatory joint pain.
Collapse
|
|
41
|
Abstract
PURPOSE OF REVIEW To review new data on pharmacologic treatment of osteoarthritis for the years 2011-2012. RECENT FINDINGS Duloxetine was approved for the treatment of chronic knee pain due to osteoarthritis and has been conditionally recommended by the American College of Rheumatology. Strontium ranelate was found to significantly decrease the rate of decline in joint space width as well as improve pain scores compared with placebo in a large multicenter study in patients with symptomatic knee osteoarthritis. Nerve growth factor (NGF) monoclonal antibody therapy has shown much promise with regard to improvement in pain; however, clinical development studies were stopped out of concern for adverse events in 2010. After a review by the Food and Drug Administration, this hold may be lifted and further studies may resume in 2013. The biologic agents interleukin-1 receptor antagonist and antitumor necrosis factor antibodies have not been shown to be efficacious nor to alter the course of osteoarthritis. Much research surrounding intra-articular injections of platelet-rich plasma (PRP) has not produced clear evidence that this therapy is efficacious in osteoarthritis. There are presently studies using mesenchymal stem cell therapy for osteoarthritis. SUMMARY Duloxetine, strontium ranelate, and NGF antibodies are promising therapies for symptomatic osteoarthritis. At this time, MSCs and PRP require more investigation.
Collapse
|
|
42
|
Abstract
Chronic musculoskeletal pain is a common cause of chronic pain, which is associated with a total cost of $635 billion per year in the U.S. Emerging evidence suggests an anti-nociceptive action of botulinum toxin, independent of its muscle paralyzing action. This review provides a summary of data from both non-randomized and randomized clinical studies of botulinum toxin in back pain and various osteoarticular conditions, including osteoarthritis, tennis elbow, low back pain and hand pain. Three randomized controlled trials (RCTs) of small sizes provide evidence of short-term efficacy of a single intra-articular injection of 100 units of botulinum toxin A (BoNT/A) for the relief of pain and the improvement of both function and quality of life in patients with chronic joint pain due to arthritis. Three RCTs studied intramuscular BoNT/A for tennis elbow with one showing a significant improvement in pain relief compared with placebo, another one showing no difference from placebo, and the third finding that pain and function improvement with BoNT/A injection were similar to those obtained with surgical release. One RCT of intramuscular BoNT/A for low back pain found improvement in pain and function compared to placebo. Single RCTs using local injections of BoNT in patients with either temporomandibular joint (TMJ) pain or plantar fasciitis found superior efficacy compared to placebo. One RCT of intramuscular BoNT/B in patients with hand pain and carpal tunnel syndrome found improvement in pain in both BoNT/B and placebo groups, but no significant difference between groups. Most evidence is based on small studies, but the use of BoNT is supported by a single, and sometimes up to three, RCTs for several chronic musculoskeletal pain conditions. This indicates that botulinum toxin may be a promising potential new treatment for chronic refractory musculoskeletal pain. Well-designed large clinical trials are needed.
Collapse
Affiliation(s)
- Jasvinder A Singh
- Medicine Service and Center for Surgical Medical Acute Care Research and Transitions (C-SMART), Birmingham Veterans Affairs Medical Center, Birmingham AL, 35294, USA ; Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama, Birmingham AL, 35294, USA ; Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester MN, 55123, USA
| |
Collapse
|
|
43
|
Hameed F, Ihm J. Injectable medications for osteoarthritis. PM R 2012; 4:S75-81. [PMID: 22632706 DOI: 10.1016/j.pmrj.2012.02.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Accepted: 02/08/2012] [Indexed: 10/28/2022]
Abstract
Osteoarthritis is one of the most frequent and chronic conditions that affect the U.S. population. Use of intra-articular injections is one of the established treatment options available in the nonoperative care for the management of symptomatic osteoarthritis. Common injectable medications include corticosteroids, hyaluronic acid, and other less traditional compounds (for example, botulinum toxin). Corticosteroids work by anti-inflammatory and antinociceptive actions. Corticosteroids have been shown to decrease pain and symptoms associated with osteoarthritis for up to 3 weeks. Hyaluronic acid has an unclear mechanism of action, but it is thought to promote the restoration of hyaluronic acid within an osteoarthritic joint. The efficacy of hyaluronic acid is modest and is most beneficial between 5 and 13 weeks after treatment. Other injectable compounds have been studied and include botulinum toxin type A, which has been theorized to work as an antinociceptive agent. One must be aware of the potential adverse effects associated with these medications. For all of these injectable treatments, the placebo effect must not be overlooked, because it has be demonstrated in multiple studies that these medications provide similar relief of pain when compared with placebo. Image guidance with ultrasound or fluoroscopy may be considered when performing intra-articular injections to improve accurate placement of medication.
Collapse
Affiliation(s)
- Farah Hameed
- Department of Physical Medicine and Rehabilitation, Rehabilitation Institute of Chicago, Chicago, IL 60611, USA
| | | |
Collapse
|
|
44
|
Mittal S, Machado DG, Jabbari B. OnabotulinumtoxinA for treatment of focal cancer pain after surgery and/or radiation. PAIN MEDICINE 2012; 13:1029-33. [PMID: 22776097 DOI: 10.1111/j.1526-4637.2012.01437.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To report the relief from refractory focal post-radiation and/or postsurgical cancer pain after local treatment with onabotulinumtoxinA. SETTING AND DESIGN We studied the effect of onabotulinumtoxinA in seven cancer patients who suffered from severe focal pain (visual analog scale >5) at the site of local surgery or radiotherapy or both. OnabotulinumtoxinA (20-100 units) was injected into the focal pain areas (skin or muscle or both). Five of seven patients were followed beyond 1 year (1.5-5 years) with repeat treatment. RESULTS All seven patients reported a significant improvement in pain (mean drop in visual analog scale score of 5.1). They described their response on the patient global assessment as satisfactory (two patients) or very satisfactory (five patients). Six of seven patients found the pain relief associated with significant improvement in quality of life. One patient developed weakness of jaw muscles after bilateral masseter injection that was not observed during second injection (reduced dose). Improvements with treatment persisted with repeat injections during long-term follow-up (five patients). CONCLUSION Local treatment with onabotulinumtoxinA can significantly reduce pain and improve quality of life in cancer patients suffering from pain in the area of surgery and radiation and was well tolerated in cancer patients.
Collapse
Affiliation(s)
- Shivam Mittal
- Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA.
| | | | | |
Collapse
|
|
45
|
Singh JA. Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold? BMC Med 2012; 10:44. [PMID: 22551396 PMCID: PMC3364907 DOI: 10.1186/1741-7015-10-44] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Accepted: 05/02/2012] [Indexed: 12/13/2022] Open
Abstract
Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA.Please see related article: http://www.biomedcentral.com/1471-2474/12/259.
Collapse
Affiliation(s)
- Jasvinder A Singh
- Medicine Service, Birmingham VA Medical Center and Department of Medicine, University of Alabama, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL 35294, USA.
| |
Collapse
|
|
46
|
Abstract
BACKGROUND Pain management is a high priority for patients with rheumatoid arthritis (RA). Despite deficiencies in research data, neuromodulators have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain. OBJECTIVES The aim of this review was to determine the efficacy and safety of neuromodulators in pain management in patients with RA. Neuromodulators included in this review were anticonvulsants (gabapentin, pregabalin, phenytoin, sodium valproate, lamotrigine, carbamazepine, levetiracetam, oxcarbazepine, tiagabine and topiramate), ketamine, bupropion, methylphenidate, nefopam, capsaicin and the cannabinoids. SEARCH METHODS We performed a computer-assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44, 2010) and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 and 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conference abstracts and performed a handsearch of reference lists of articles. SELECTION CRITERIA We included randomised controlled trials which compared any neuromodulator to another therapy (active or placebo, including non-pharmacological therapies) in adult patients with RA that had at least one clinically relevant outcome measure. DATA COLLECTION AND ANALYSIS Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta-analyses were used to examine the efficacy of a neuromodulator on pain, depression and function as well as their safety. MAIN RESULTS Four trials with high risk of bias were included in this review. Two trials evaluated oral nefopam (52 participants) and one trial each evaluated topical capsaicin (31 participants) and oromucosal cannabis (58 participants).The pooled analyses identified a significant reduction in pain levels favouring nefopam over placebo (weighted mean difference (WMD) -21.16, 95% CI -35.61 to -6.71; number needed to treat (NNT) 2, 95% CI 1.4 to 9.5) after two weeks. There were insufficient data to assess withdrawals due to adverse events. Nefopam was associated with significantly more adverse events (RR 4.11, 95% CI 1.58 to 10.69; NNTH 9, 95% CI 2 to 367), which were predominantly nausea and sweating.In a mixed population trial, qualitative analysis of patients with RA showed a significantly greater reduction in pain favouring topical capsaicin over placebo at one and two weeks (MD -23.80, 95% CI -44.81 to -2.79; NNT 3, 95% CI 2 to 47; MD -34.40, 95% CI -54.66 to -14.14; NNT 2, 95% CI 1.4 to 6 respectively). No separate safety data were available for patients with RA, however 44% of patients developed burning at the site of application and 2% withdrew because of this.One small, low quality trial assessed oromucosal cannabis against placebo and found a small, significant difference favouring cannabis in the verbal rating score 'pain at present' (MD -0.72, 95% CI -1.31 to -0.13) after five weeks. Patients receiving cannabis were significantly more likely to suffer an adverse event (risk ratio (RR) 1.82, 95% CI 1.10 to 3.00; NNTH 3, 95% CI 3 to 13). These were most commonly dizziness (26%), dry mouth (13%) and light headedness (10%). AUTHORS' CONCLUSIONS There is currently weak evidence that oral nefopam, topical capsaicin and oromucosal cannabis are all superior to placebo in reducing pain in patients with RA. However, each agent is associated with a significant side effect profile. The confidence in our estimates is not strong given the difficulties with blinding, the small numbers of participants evaluated and the lack of adverse event data. In some patients, however, even a small degree of pain relief may be considered worthwhile. Until further research is available, given the relatively mild nature of the adverse events, capsaicin could be considered as an add-on therapy for patients with persistent local pain and inadequate response or intolerance to other treatments. Oral nefopam and oromucosal cannabis have more significant side effect profiles however and the potential harms seem to outweigh any modest benefit achieved.
Collapse
Affiliation(s)
- Bethan L Richards
- Institute of Rheumatology and Orthopedics, Royal Prince Alfred Hospital, Camperdown, Australia.
| | | | | |
Collapse
|
|
47
|
Jabbari B, Machado D. Treatment of refractory pain with botulinum toxins--an evidence-based review. PAIN MEDICINE 2011; 12:1594-606. [PMID: 21958302 DOI: 10.1111/j.1526-4637.2011.01245.x] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVES To provide updated information on the role of botulinum toxins in the treatment of refractory pain based on prospective, randomized, double-blind, placebo-controlled studies. DESIGN OF THE REVIEW: Class I and class II articles were searched online through PubMed (1966 to the end of January 2011) and OvidSP including ahead-of-print manuscripts. RESULTS Level A evidence (two or more class I studies-established efficacy): pain of cervical dystonia, chronic migraine, and chronic lateral epicondylitis. Level B evidence (one class I or two class II studies-probably effective and recommended): post-herpetic neuralgia, post-traumatic neuralgia, pain of plantar fasciitis, piriformis syndrome, and pain in total knee arthroplasty. Level C evidence (one class II study-possibly effective, may be used at discretion of clinician): allodynia of diabetic neuropathy, chronic low back pain, painful knee osteoarthritis, anterior knee pain with vastus lateralis imbalance, pelvic pain, post-operative pain in children with cerebral palsy after adductor hip release surgery, post-operative pain after mastectomy, and sphincter spasms and pain after hemorrhoidectomy. Level U evidence (efficacy not proven due to diverse class I and II results): myofascial pain syndrome and chronic daily headaches. Studies in episodic migraine and tension headaches have shown treatment failure (level A-negative). CONCLUSION Evidence-based data indicate that administration of botulinum toxin in several human conditions can alleviate refractory pain. The problems with some study designs and toxin dosage are critically reviewed.
Collapse
Affiliation(s)
- Bahman Jabbari
- Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
| | | |
Collapse
|
|
48
|
Castiglione A, Bagnato S, Boccagni C, Romano MC, Galardi G. Efficacy of intra-articular injection of botulinum toxin type A in refractory hemiplegic shoulder pain. Arch Phys Med Rehabil 2011; 92:1034-7. [PMID: 21704782 DOI: 10.1016/j.apmr.2011.01.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2010] [Revised: 01/24/2011] [Accepted: 01/27/2011] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To evaluate the efficacy of intra-articular injection of botulinum toxin type A (BTX-A) in relieving hemiplegic shoulder pain (HSP). DESIGN Pilot study with assessments before and after BTX-A intra-articular injection. SETTING Hospital rehabilitation department. PARTICIPANTS Patients (N=5) with HSP refractory to standard treatments and pain score at rest greater than 7 on a pain visual analog scale (VAS) of 0 to 10cm. INTERVENTION Intra-articular BTX-A injection. MAIN OUTCOME MEASURE Variation in VAS score at rest and during 90° passive arm abduction 2 and 8 weeks after BTX-A intra-articular injection. RESULTS Baseline VAS score was 8.7±1 at rest and 9.8±0.4 during passive arm abduction. It clearly decreased at 2 (1.5±1.1 at rest, P=.001; 3±1.2 during arm abduction, P<.001) and 8 weeks (1.5±1.2 at rest, P=.001; 2.3±1.1 during arm abduction, P<.001) after BTX-A intra-articular injection. CONCLUSIONS We found a strong correlation between intra-articular BTX-A injection and pain relief in patients with HSP. This result could provide the rationale for blind randomized controlled trials designed to better evaluate the safety and efficacy of intra-articular BTX-A injection in patients with refractory HSP.
Collapse
Affiliation(s)
- Alberto Castiglione
- Department of Rehabilitation, Fondazione Istituto San Raffaele-G. Giglio, Cefalù Palermo, Italy
| | | | | | | | | |
Collapse
|
|
49
|
|
|
50
|
Iannitti T, Lodi D, Palmieri B. Intra-articular injections for the treatment of osteoarthritis: focus on the clinical use of hyaluronic acid. Drugs R D 2011; 11:13-27. [PMID: 21142290 PMCID: PMC3586124 DOI: 10.2165/11539760-000000000-00000] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Osteoarthritis (OA), also called degenerative joint disease, is the most frequently occurring chronic musculoskeletal disease, particularly affecting the aging population. The use of viscosupplementation, i.e. intra-articular (IA) hyaluronic acid (HA) drug therapy, to treat OA, is growing worldwide, due to important results obtained from several clinical trials, which reported IA HA-related improvements in functional activity and pain management. This review is an update of the IA use of this compound in the treatment of OA, with clinical evidence from the last few years being discussed and used to delineate new trends for the future.
Collapse
Affiliation(s)
- Tommaso Iannitti
- Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK.
| | | | | |
Collapse
|