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Ye Z, Yang S, Lu L, Zong M, Fan L, Kang C. Unlocking the potential of the 3-hydroxykynurenine/kynurenic acid ratio: a promising biomarker in adolescent major depressive disorder. Eur Arch Psychiatry Clin Neurosci 2024:10.1007/s00406-024-01815-x. [PMID: 38819463 DOI: 10.1007/s00406-024-01815-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 04/19/2024] [Indexed: 06/01/2024]
Abstract
Metabolites disruptions in tryptophan (TRP) and kynurenine pathway (KP) are believed to disturb neurotransmitter homeostasis and contribute to depressive symptoms. This study aims to investigate serum levels of KP metabolites in adolescent major depressive disorder (AMDD), and examine their relationship with depression severities. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze serum levels of TRP, kynurenic acid (KYNA), kynurenine (KYN), and 3-hydroxy-kynurenine (3-HK) in 143 AMDD participants and 98 healthy controls (HC). Clinical data, including Children's Depression Inventory (CDI) scores, were collected and analyzed using statistical methods, such as ANOVA, logistic regression, Receiver operating characteristic curve analysis and a significance level of p < 0.05 was used for all analyses. AMDD showed significantly decreased serum levels of KYNA (-25.5%), KYN (-14.2%), TRP (-11.0%) and the KYNA/KYN ratio (-11.9%) compared to HC (p < 0.01). Conversely, significant increases were observed in 3-HK levels (+50.4%), the 3-HK/KYNA ratio (+104.3%) and the 3-HK/KYN ratio (+93.0%) (p < 0.01). Logistic regression analysis identified increased level of 3-HK as a contributing factor to AMDD, while increased level of KYNA acted as a protective factor against AMDD. The 3-HK/KYNA ratio demonstrated an area under the curve (AUC) of 0.952. This study didn't explore AMDD's inflammatory status and its metabolites relationship explicitly. These findings indicate that metabolites of TRP and KP may play a crucial role in the pathogenesis of AMDD, emphasizing the potential of the 3-HK/KYNA ratio as a laboratory biomarker for early detection and diagnosis of AMDD.
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Affiliation(s)
- Zhihan Ye
- Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji Mo Road, Shanghai, 200120, China
| | - Shuran Yang
- Department of Psychosomatic Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji Mo Road, Shanghai, 200120, China
| | - Liu Lu
- Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji Mo Road, Shanghai, 200120, China
| | - Ming Zong
- Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji Mo Road, Shanghai, 200120, China
| | - Lieying Fan
- Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji Mo Road, Shanghai, 200120, China
| | - Chuanyuan Kang
- Department of Psychosomatic Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji Mo Road, Shanghai, 200120, China.
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The Welfare of Fighting Dogs: Wounds, Neurobiology of Pain, Legal Aspects and the Potential Role of the Veterinary Profession. Animals (Basel) 2022; 12:ani12172257. [PMID: 36077977 PMCID: PMC9454875 DOI: 10.3390/ani12172257] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 11/21/2022] Open
Abstract
Simple Summary Dog fights are cruel and harmful events which have a clear impact on animal welfare. For this reason, many countries have banned these events via statute. However, in some regions of the world they are still legal. Moreover, the enforcement of legal bans can be problematic in countries where they are illegal, and they may still occur. This article provides background information on dog fighting and the welfare implications of it. This includes consideration for the pain inflicted, and its mechanisms of perception and recognition. It also analyzes the injuries and emotions experienced by the animals and considers the profile of the breeders and handlers involved in the activity. Since welfare concerns often extend beyond the animals’ fighting lives, a discussion around the possibilities of reintroduction into suitable environments for these animals is also made. Finally, attention is turned to the role that veterinarians can and should play in dealing with these issues of welfare. Abstract Throughout history it has been common to practice activities which significantly impact on animal welfare. Animal fighting, including dogfighting, is a prime example where animals often require veterinary care, either to treat wounds and fractures or to manage pain associated with tissue and where death may even result. Amongst the detrimental health effects arising are the sensory alterations that these injuries cause, which not only include acute or chronic pain but can also trigger a greater sensitivity to other harmful (hyperalgesia) or even innocuous stimuli (allodynia). These neurobiological aspects are often ignored and the erroneous assumption made that the breeds engaged in organized fighting have a high pain threshold or, at least, they present reduced or delayed responses to painful stimuli. However, it is now widely recognized that the damage these dogs suffer is not only physical but psychological, emotional, and sensory. Due to the impact fighting has on canine welfare, it is necessary to propose solution strategies, especially educational ones, i.e., educating people and training veterinarians, the latter potentially playing a key role in alerting people to all dog welfare issues. Therefore, the aim of this review is to describe the risk factors associated with dogfighting generally (dog temperament, age, sex, nutrition, testosterone levels, environment, isolation conditions, socialization, education, or training). A neurobiological approach to this topic is taken to discuss the impact on dog pain and emotion. Finally, a general discussion of the format of guidelines and laws that seek to sanction them is presented. The role that veterinarians can play in advancing dog welfare, rehabilitating dogs, and educating the public is also considered.
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Li YX, Li JH, Guo Y, Tao ZY, Qin SH, Traub RJ, An H, Cao DY. Oxytocin inhibits hindpaw hyperalgesia induced by orofacial inflammation combined with stress. Mol Pain 2022; 18:17448069221089591. [PMID: 35266833 PMCID: PMC9047792 DOI: 10.1177/17448069221089591] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Oxytocin (OT) is recognized as a critical neuropeptide in pain-related disorders. Chronic pain caused by the comorbidity of temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) is common, but whether OT plays an analgesic role in the comorbidity of TMD and FMS is unknown. Female rats with masseter muscle inflammation combined with 3-day forced swim (FS) stress developed somatic hypersensitivity, which modeled the comorbidity of TMD and FMS. Using this model, the effects of spinal OT administration on mechanical allodynia and thermal hyperalgesia in hindpaws were examined. Furthermore, the protein levels of OT receptors and 5-HT2A receptors in the L4-L5 spinal dorsal horn were analyzed by Western blot. The OT receptor antagonist atosiban and 5-HT2A receptor antagonist ritanserin were intrathecally injected prior to OT injection in the separate groups. Intrathecal injection of 0.125 μg and 0.5 μg OT attenuated the hindpaw hyperalgesia. The expression of OT receptors and 5-HT2A receptors in the L4-L5 spinal dorsal horn significantly increased following intrathecal injection of 0.5 μg OT. Intrathecal administration of either the OT receptor antagonist atosiban or 5-HT2A receptor antagonist ritanserin blocked the analgesic effect of OT. These results suggest that OT may inhibit hindpaw hyperalgesia evoked by orofacial inflammation combined with stress through OT receptors and/or 5-HT2A receptors, thus providing a therapeutic prospect for drugs targeting the OT system and for patients with comorbidity of TMD and FMS.
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Affiliation(s)
- Yue-Xin Li
- Key Laboratory of Shaanxi Province
for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi’an Jiaotong University College of
Stomatology, China
- Department of Special Dental Care, Xi’an Jiaotong University College of
Stomatology, China
| | - Jia-Heng Li
- Key Laboratory of Shaanxi Province
for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi’an Jiaotong University College of
Stomatology, China
| | - Yi Guo
- Key Laboratory of Shaanxi Province
for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi’an Jiaotong University College of
Stomatology, China
| | - Zhuo-Ying Tao
- Key Laboratory of Shaanxi Province
for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi’an Jiaotong University College of
Stomatology, China
| | - Shi-Hao Qin
- Key Laboratory of Shaanxi Province
for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi’an Jiaotong University College of
Stomatology, China
- Department of Special Dental Care, Xi’an Jiaotong University College of
Stomatology, China
| | - Richard J Traub
- Department of Neural and Pain
Sciences, School of Dentistry, Center to Advance Chronic Pain Research, University of Maryland
Baltimore, Baltimore, MD, USA
| | - Hong An
- Department of Special Dental Care, Xi’an Jiaotong University College of
Stomatology, China
| | - Dong-Yuan Cao
- Key Laboratory of Shaanxi Province
for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi’an Jiaotong University College of
Stomatology, China
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Efficacy and acceptability of a second dose of ecological executive skills training for children with ADHD: a randomized controlled study and follow-up. Eur Child Adolesc Psychiatry 2021; 30:921-935. [PMID: 32596788 DOI: 10.1007/s00787-020-01571-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 06/01/2020] [Indexed: 01/18/2023]
Abstract
To explore the efficacy and acceptability of a second dose of the 12-session ecological executive skills training (EEST) 1 year after the initial training in children with ADHD. A total of 97 children (aged 6-12) with ADHD who finished the first dose for about 1 year were recruited in the current study. 70 children who agreed to participate the second dose were randomized to the second dose or waitlist group. Both groups were followed up 1 year after the second dose. Executive function, core symptoms were assessed at the time of pre-intervention first dose, pre-intervention second dose, post-intervention second dose and follow-up 1 year after second dose (phase 0-3). For the immediate efficacy, the improvements in the second dose group were greater than the waitlist group on planning by Stockings of Cambridge and delay aversion by Cambridge gambling task (P = 0.02-0.04, η2 = 0.07-0.08). The parent rating of symptoms assessed by ADHD-RS-IV of the second dose group were also greater than the waitlist group rated by self-report. For long term efficacy, Linear mixed model indicated that there was significant time effect for both groups between phase 3 and phase 1, phase 1 and phase 0 on Behavior Rating Scales of Executive Function and ADHD-RS-IV (F = 2.849-21.560, P = 0.001-0.048). The compliance rate was 94.3% for the second dose group and 49% for waitlist group. A second dose of EEST program might bring further efficacy of EF and core symptoms for children with ADHD and it was well accepted.
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Tong J, Yu W, Fan X, Sun X, Zhang J, Zhang J, Zhang T. Impact of Group Art Therapy Using Traditional Chinese Materials on Self-Efficacy and Social Function for Individuals Diagnosed With Schizophrenia. Front Psychol 2021; 11:571124. [PMID: 33551897 PMCID: PMC7855174 DOI: 10.3389/fpsyg.2020.571124] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 12/16/2020] [Indexed: 11/13/2022] Open
Abstract
The purpose of this study was to examine the effect of group art therapy using traditional Chinese materials on improving the self-efficacy and social function of individuals diagnosed with schizophrenia. In China, little research has been conducted on patients to measure the effectiveness of group art therapy, especially using traditional Chinese materials. To address this research gap, 104 individuals diagnosed with schizophrenia were tested in a group art therapy program that included 30 treatment sessions and used a wide variety of materials, including traditional Chinese materials, such as Chinese calligraphy, traditional Chinese painting, Chinese embroidery, and Chinese beads. The effect of art therapy was analyzed using the General Self-Efficacy Scale (GSES) and Scale of Social Skills for Psychiatric Inpatients (SSPI). This study demonstrates that group art therapy using traditional Chinese materials can improve self-efficacy and social function, reducing social and life function problems, and promote the recovery of individuals diagnosed with schizophrenia.
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Affiliation(s)
| | - Wei Yu
- Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China
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Kissiwaa SA, Patel SD, Winters BL, Bagley EE. Opioids differentially modulate two synapses important for pain processing in the amygdala. Br J Pharmacol 2020; 177:420-431. [PMID: 31596498 PMCID: PMC6989950 DOI: 10.1111/bph.14877] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 08/04/2019] [Accepted: 08/09/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND AND PURPOSE Pain is a subjective experience involving sensory discriminative and emotionally aversive components. Consistent with its role in pain processing and emotions, the amygdala modulates the aversive component of pain. The laterocapsular region of the central nucleus of the amygdala (CeLC) receives nociceptive information from the parabrachial nucleus (PB) and polymodal, including nociceptive, inputs from the basolateral nucleus of the amygdala (BLA). Opioids are strong analgesics and reduce both the sensory discriminative and the affective component of pain. However, it is unknown whether opioids regulate activity at the two nociceptive inputs to the amygdala. EXPERIMENTAL APPROACH Using whole-cell electrophysiology, optogenetics, and immunohistochemistry, we investigated whether opioids inhibit the rat PB-CeLC and BLA-CeLC synapses. KEY RESULTS Opioids inhibited glutamate release at the PB-CeLC and BLA-CeLC synapses. Opioid inhibition is via the μ-receptor at the PB-CeLC synapse, while at the BLA-CeLC synapse, inhibition is via μ-receptors in all neurons and via δ-receptors and κ-receptors in a subset of neurons. CONCLUSIONS AND IMPLICATIONS Agonists of μ-receptors inhibited two of the synaptic inputs carrying nociceptive information into the laterocapsular amygdala. Therefore, μ-receptor agonists, such as morphine, will inhibit glutamate release from PB and BLA in the CeLC, and this could serve as a mechanism through which opioids reduce the affective component of pain and pain-induced associative learning. The lower than expected regulation of BLA synaptic outputs by δ-receptors does not support the proposal that opioid receptor subtypes segregate into subnuclei of brain regions.
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MESH Headings
- Amygdala/drug effects
- Amygdala/metabolism
- Amygdala/physiopathology
- Analgesics, Opioid/pharmacology
- Animals
- Glutamic Acid/metabolism
- Male
- Neural Inhibition/drug effects
- Nociception/drug effects
- Nociceptive Pain/metabolism
- Nociceptive Pain/physiopathology
- Nociceptive Pain/prevention & control
- Optogenetics
- Pain Perception/drug effects
- Rats, Sprague-Dawley
- Receptors, Opioid, delta/agonists
- Receptors, Opioid, delta/metabolism
- Receptors, Opioid, kappa/agonists
- Receptors, Opioid, kappa/metabolism
- Receptors, Opioid, mu/agonists
- Receptors, Opioid, mu/metabolism
- Synapses/drug effects
- Synapses/metabolism
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Affiliation(s)
- Sarah A. Kissiwaa
- Discipline of Pharmacology and Charles Perkins CentreThe University of SydneySydneyNSWAustralia
| | - Sahil D. Patel
- Discipline of Pharmacology and Charles Perkins CentreThe University of SydneySydneyNSWAustralia
| | - Bryony L. Winters
- Pain Management Research Institute, Kolling Institute of Medical ResearchThe University of Sydney, Royal North Shore HospitalSt LeonardsNSWAustralia
| | - Elena E. Bagley
- Discipline of Pharmacology and Charles Perkins CentreThe University of SydneySydneyNSWAustralia
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Xie X, Zhang M, Qiao J. The magnet sorting of APTRON. THE REVIEW OF SCIENTIFIC INSTRUMENTS 2020; 91:014711. [PMID: 32012565 DOI: 10.1063/1.5125177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 01/07/2020] [Indexed: 06/10/2023]
Abstract
The magnetic field error caused by imperfection during the manufacturing process of magnets is inevitable. Therefore, the field error of both dipole and quadrupole magnets and their alignment errors will cause the synchrotron closed orbit distortion. In order to minimize the influence of the beam, a sorting method is applied to both dipole and quadrupole magnets with integral consideration of different excitation currents, covering both low and high field situations. The commissioning result shows that we can achieve the designed beam intensity.
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Affiliation(s)
- Xiucui Xie
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
| | - Manzhou Zhang
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
| | - Jian Qiao
- Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
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Turner PV, Pang DS, Lofgren JL. A Review of Pain Assessment Methods in Laboratory Rodents. Comp Med 2019; 69:451-467. [PMID: 31896391 PMCID: PMC6935698 DOI: 10.30802/aalas-cm-19-000042] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 05/29/2019] [Accepted: 07/09/2019] [Indexed: 12/22/2022]
Abstract
Ensuring that laboratory rodent pain is well managed underpins the ethical acceptability of working with these animals in research. Appropriate treatment of pain in laboratory rodents requires accurate assessments of the presence or absence of pain to the extent possible. This can be challenging some situations because laboratory rodents are prey species that may show subtle signs of pain. Although a number of standard algesiometry assays have been used to assess evoked pain responses in rodents for many decades, these methods likely represent an oversimplification of pain assessment and many require animal handling during testing, which can result in stress-induced analgesia. More recent pain assessment methods, such as the use of ethograms, facial grimace scoring, burrowing, and nest-building, focus on evaluating changes in spontaneous behaviors or activities of rodents in their home environments. Many of these assessment methods are time-consuming to conduct. While many of these newer tests show promise for providing a more accurate assessment of pain, most require more study to determine their reliability and sensitivity across a broad range of experimental conditions, as well as between species and strains of animals. Regular observation of laboratory rodents before and after painful procedures with consistent use of 2 or more assessment methods is likely to improve pain detection and lead to improved treatment and care-a primary goal for improving overall animal welfare.
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Affiliation(s)
- Patricia V Turner
- Charles River, Wilmington , Massachusetts Dept of Pathobiology, University of Guelph, Guelph, Canada;,
| | - Daniel Sj Pang
- Dept of Clinical Sciences, Université de Montréal, Quebec, J2S 2M2, Veterinary Clinical and Diagnostic Sciences, University of Calgary, Alberta, Canada
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Tumor necrosis factor receptor 1 inhibition is therapeutic for neuropathic pain in males but not in females. Pain 2019; 160:922-931. [PMID: 30586024 DOI: 10.1097/j.pain.0000000000001470] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is involved in physiological and pathological processes and has been found to be crucial for pain development. In the current study, we were interested in the effects of blocking Tumor necrosis factor receptor 1 (TNFR1) signaling on neuropathic pain after peripheral nerve injury with the use of transgenic mice and pharmacological inhibition. We have previously shown that TNFR1 mice failed to develop neuropathic pain and depressive symptoms after chronic constriction injury (CCI). To investigate the therapeutic effects of inhibiting TNFR1 signaling after injury, we delivered a drug that inactivates soluble TNF (XPro1595). Inhibition of solTNF signaling resulted in an accelerated recovery from neuropathic pain in males, but not in females. To begin exploring a mechanism, we investigated changes in N-methyl-D-aspartate (NMDA) receptors because neuropathic pain has been shown to invoke an increase in glutamatergic signaling. In male mice, XPro1595 treatment reduces elevated NMDA receptor levels in the brain after injury, whereas in female mice, NMDA receptor levels decrease after CCI. We further show that estrogen inhibits the therapeutic response of XPro1595 in females. Our results suggest that TNFR1 signaling plays an essential role in pain induction after CCI in males but not in females.
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Hu SM, Chen MS, Tan HZ. Maternal serum level of resistin is associated with risk for gestational diabetes mellitus: A meta-analysis. World J Clin Cases 2019; 7:585-599. [PMID: 30863758 PMCID: PMC6406206 DOI: 10.12998/wjcc.v7.i5.585] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 02/02/2019] [Accepted: 02/18/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Resistin is most likely involved in the pathogenesis of gestational diabetes mellitus (GDM), but the existing findings are inconsistent.
AIM To review the literature investigating the associations of the risk of GDM with serum level of resistin.
METHODS A systematic literature search was performed using MEDLINE, EMBASE, and Web of Science (all databases). This meta-analysis included eligible studies that: (1) investigated the relationship between the risk of GDM and serum resistin; (2) included GDM cases and controls without GDM; (3) diagnosed GDM according to the oral glucose-tolerance test; (4) were performed in humans; (5) were published as full text articles in English; and (6) provided data with median and quartile range, median and minimum and maximum values, or mean and standard deviation. The pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated to estimate the association between the risk of GDM and serum resistin. To analyze the potential influences of need for insulin in GDM patients and gestational age at blood sampling, we performed a subgroup analysis. Meta-regression with restricted maximum likelihood estimation was performed to assess the potentially important covariate exerting substantial impact on between-study heterogeneity.
RESULTS The meta-analysis for the association between serum resistin level and GDM risk included 18 studies (22 comparisons) with 1041 cases and 1292 controls. The total results showed that the risk of GDM was associated with higher serum resistin level (SMD = 0.250, 95%CI: 0.116, 0.384). The “after 28 wk” subgroup, “no need for insulin” subgroup, and “need for insulin” subgroup indicated that higher serum resistin level was related to GDM risk (“after 28 wk” subgroup: SMD = 0.394, 95%CI: 0.108, 0.680; “no need for insulin” subgroup: SMD = 0.177, 95%CI: 0.018, 0.336; “need for insulin” subgroup: SMD = 0.403, 95%CI: 0.119, 0.687). The “before 14 wk” subgroup, “14-28 wk” subgroup, and “no information of need for insulin” subgroup showed a nonsignificant association between serum resistin level and GDM risk (“before 14 wk” subgroup: SMD = 0.087, 95%CI: -0.055, 0.230; “14-28 wk” subgroup: SMD = 0.217, 95%CI: -0.003, 0.436; “no information of need for insulin” subgroup: SMD = 0.356, 95%CI: -0.143, 0.855). The postpartum subgroup included only one study and showed that higher serum resistin level was related to GDM risk (SMD = 0.571, 95%CI: 0.054, 1.087) The meta-regression revealed that no need for insulin in GDM patients, age distribution similar between cases and controls, and ELISA all had a significant impact on between-study heterogeneity.
CONCLUSION This meta-analysis supports that the maternal serum resistin level is associated with GDM risk.
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Affiliation(s)
- Shi-Min Hu
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
| | - Meng-Shi Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
| | - Hong-Zhuan Tan
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
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Kissiwaa SA, Bagley EE. Central sensitization of the spino-parabrachial-amygdala pathway that outlasts a brief nociceptive stimulus. J Physiol 2018; 596:4457-4473. [PMID: 30004124 PMCID: PMC6138295 DOI: 10.1113/jp273976] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 06/29/2018] [Indexed: 12/22/2022] Open
Abstract
KEY POINTS Chronic pain is disabling because sufferers form negative associations between pain and activities, such as work, leading to the sufferer limiting these activities. Pain information arriving in the amygdala is responsible for forming these associations and contributes to us feeling bad when we are in pain. Ongoing injuries enhance the delivery of pain information to the amygdala. If we want to understand why chronic pain can continue without ongoing injury, it is important to know whether this facilitation continues once the injury has healed. In the present study, we show that a 2 min noxious heat stimulus, without ongoing injury, is able to enhance delivery of pain information to the amygdala for 3 days. If the noxious heat stimulus is repeated, this enhancement persists even longer. These changes may prime this information pathway so that subsequent injuries may feel even worse and the associative learning that results in pain-related avoidance may be promoted. ABSTRACT Pain is an important defence against dangers in our environment; however, some clinical conditions produce pain that outlasts this useful role and persists even after the injury has healed. The experience of pain consists of somatosensory elements of intensity and location, negative emotional/aversive feelings and subsequent restrictions on lifestyle as a result of a learned association between certain activities and pain. The amygdala contributes negative emotional value to nociceptive sensory information and forms the association between an aversive response and the environment in which it occurs. It is able to form this association because it receives nociceptive information via the spino-parabrachio-amygdaloid pathway and polymodal sensory information via cortical and thalamic inputs. Synaptic plasticity occurs at the parabrachial-amygdala synapse and other brain regions in chronic pain conditions with ongoing injury; however, very little is known about how plasticity occurs in conditions with no ongoing injury. Using immunohistochemistry, electrophysiology and behavioural assays, we show that a brief nociceptive stimulus with no ongoing injury is able to produce long-lasting synaptic plasticity at the rat parabrachial-amygdala synapse. We show that this plasticity is caused by an increase in postsynaptic AMPA receptors with a transient change in the AMPA receptor subunit, similar to long-term potentiation. Furthermore, this synaptic potentiation primes the synapse so that a subsequent noxious stimulus causes prolonged potentiation of the nociceptive information flow into the amygdala. As a result, a second injury could have an increased negative emotional value and promote associative learning that results in pain-related avoidance.
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Affiliation(s)
- Sarah A Kissiwaa
- Discipline of Pharmacology and Charles Perkins CentreUniversity of SydneySydneyNSW2006Australia
| | - Elena E Bagley
- Discipline of Pharmacology and Charles Perkins CentreUniversity of SydneySydneyNSW2006Australia
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12
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Affiliation(s)
- Jordan Raine
- Mammal Vocal Communication and Cognition Research Group, School of Psychology, University of Sussex, Brighton, UK
| | - Katarzyna Pisanski
- Mammal Vocal Communication and Cognition Research Group, School of Psychology, University of Sussex, Brighton, UK
| | - Julia Simner
- MULTISENSE Research Lab, School of Psychology, University of Sussex, Brighton, UK
| | - David Reby
- Mammal Vocal Communication and Cognition Research Group, School of Psychology, University of Sussex, Brighton, UK
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13
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Otis C, Gervais J, Guillot M, Gervais JA, Gauvin D, Péthel C, Authier S, Dansereau MA, Sarret P, Martel-Pelletier J, Pelletier JP, Beaudry F, Troncy E. Concurrent validity of different functional and neuroproteomic pain assessment methods in the rat osteoarthritis monosodium iodoacetate (MIA) model. Arthritis Res Ther 2016; 18:150. [PMID: 27338815 PMCID: PMC4918125 DOI: 10.1186/s13075-016-1047-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 06/09/2016] [Indexed: 11/17/2022] Open
Abstract
Background Lack of validity in osteoarthritis pain models and assessment methods is suspected. Our goal was to 1) assess the repeatability and reproducibility of measurement and the influence of environment, and acclimatization, to different pain assessment outcomes in normal rats, and 2) test the concurrent validity of the most reliable methods in relation to the expression of different spinal neuropeptides in a chemical model of osteoarthritic pain. Methods Repeatability and inter-rater reliability of reflexive nociceptive mechanical thresholds, spontaneous static weight-bearing, treadmill, rotarod, and operant place escape/avoidance paradigm (PEAP) were assessed by the intraclass correlation coefficient (ICC). The most reliable acclimatization protocol was determined by comparing coefficients of variation. In a pilot comparative study, the sensitivity and responsiveness to treatment of the most reliable methods were tested in the monosodium iodoacetate (MIA) model over 21 days. Two MIA (2 mg) groups (including one lidocaine treatment group) and one sham group (0.9 % saline) received an intra-articular (50 μL) injection. Results No effect of environment (observer, inverted circadian cycle, or exercise) was observed; all tested methods except mechanical sensitivity (ICC <0.3), offered good repeatability (ICC ≥0.7). The most reliable acclimatization protocol included five assessments over two weeks. MIA-related osteoarthritic change in pain was demonstrated with static weight-bearing, punctate tactile allodynia evaluation, treadmill exercise and operant PEAP, the latter being the most responsive to analgesic intra-articular lidocaine. Substance P and calcitonin gene-related peptide were higher in MIA groups compared to naive (adjusted P (adj-P) = 0.016) or sham-treated (adj-P = 0.029) rats. Repeated post-MIA lidocaine injection resulted in 34 times lower downregulation for spinal substance P compared to MIA alone (adj-P = 0.029), with a concomitant increase of 17 % in time spent on the PEAP dark side (indicative of increased comfort). Conclusion This study of normal rats and rats with pain established the most reliable and sensitive pain assessment methods and an optimized acclimatization protocol. Operant PEAP testing was more responsive to lidocaine analgesia than other tests used, while neuropeptide spinal concentration is an objective quantification method attractive to support and validate different centralized pain functional assessment methods.
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Affiliation(s)
- Colombe Otis
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada.,Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada
| | - Julie Gervais
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada
| | - Martin Guillot
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada.,Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada
| | - Julie-Anne Gervais
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada
| | - Dominique Gauvin
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada.,Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada
| | - Catherine Péthel
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada.,Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | | | - Marc-André Dansereau
- Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Philippe Sarret
- Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Johanne Martel-Pelletier
- Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada
| | - Jean-Pierre Pelletier
- Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada
| | - Francis Beaudry
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada.,Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada
| | - Eric Troncy
- Groupe de Recherche en Pharmacologie Animale du Québec (GREPAQ), Department of Biomedical Sciences, Faculty of veterinary medicine, Université de Montréal, 1500 des Vétérinaires Street, P.O. Box 5000, St-Hyacinthe, Quebec, J2S 7C6, Canada. .,Osteoarthritis Research Unit, Research Center Hospital of Montreal University (CRCHUM), Montreal, Quebec, Canada.
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Castel D, Sabbag I, Brenner O, Meilin S. Peripheral Neuritis Trauma in Pigs: A Neuropathic Pain Model. THE JOURNAL OF PAIN 2016; 17:36-49. [DOI: 10.1016/j.jpain.2015.09.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 09/21/2015] [Accepted: 09/26/2015] [Indexed: 12/29/2022]
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15
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Pain and pessimism: dairy calves exhibit negative judgement bias following hot-iron disbudding. PLoS One 2013; 8:e80556. [PMID: 24324609 PMCID: PMC3851165 DOI: 10.1371/journal.pone.0080556] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 10/03/2013] [Indexed: 11/19/2022] Open
Abstract
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, but emotional states are difficult to directly assess in animals. Researchers have assessed pain using behavioural and physiological measures, but these approaches are limited to understanding the arousal rather than valence of the emotional experience. Cognitive bias tasks show that depressed humans judge ambiguous events negatively and this technique has been applied to assess emotional states in animals. However, limited research has examined how pain states affect cognitive processes in animals. Here we present the first evidence of cognitive bias in response to pain in any non-human species. In two experiments, dairy calves (n = 17) were trained to respond differentially to red and white video screens and then tested with unreinforced ambiguous colours in two or three test sessions before and two sessions after the routine practice of hot-iron disbudding. After disbudding calves were more likely to judge ambiguous colours as negative. This ‘pessimistic’ bias indicates that post-operative pain following hot-iron disbudding results in a negative change in emotional state.
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16
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Disturbances in slow-wave sleep are induced by models of bilateral inflammation, neuropathic, and postoperative pain, but not osteoarthritic pain in rats. Pain 2013; 154:1092-102. [DOI: 10.1016/j.pain.2013.03.019] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Revised: 01/31/2013] [Accepted: 03/12/2013] [Indexed: 11/19/2022]
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17
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Schwarting RKW, Wöhr M. On the relationships between ultrasonic calling and anxiety-related behavior in rats. Braz J Med Biol Res 2012; 45:337-48. [PMID: 22437483 PMCID: PMC3854164 DOI: 10.1590/s0100-879x2012007500038] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Accepted: 03/08/2012] [Indexed: 11/22/2022] Open
Abstract
In the present review, the phenomenon of ultrasonic vocalization in rats will be outlined, including the three classes of vocalizations, namely 40-kHz calls of pups, and 22- and 50-kHz calls of juvenile and adult rats, their general relevance to behavioral neuroscience, and their special relevance to research on anxiety, fear, and defense mechanisms. Here, the emphasis will be placed on 40- and 22-kHz calls, since they are typical for various situations with aversive properties. Among other topics, we will discuss whether such behavioral signals can index a certain affective state, and how these signals can be used in social neuroscience, especially with respect to communication. Furthermore, we will address the phenomenon of inter-individual variability in ultrasonic calling and what we currently know about the mechanisms, which may determine such variability. Finally, we will address the current knowledge on the neural and pharmacological mechanisms underlying 22-kHz ultrasonic vocalization, which show a substantial overlap with mechanisms known from other research on fear and anxiety, such as those involving the periaqueductal gray or the amygdala.
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Affiliation(s)
- R K W Schwarting
- Experimental and Physiological Psychology, Philipps-University of Marburg, Germany.
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18
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Umberg EN, Pothos EN. Neurobiology of aversive states. Physiol Behav 2011; 104:69-75. [PMID: 21549137 DOI: 10.1016/j.physbeh.2011.04.045] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2011] [Revised: 04/23/2011] [Accepted: 04/26/2011] [Indexed: 12/01/2022]
Abstract
Hoebel and colleagues are often known as students of reward and how it is coded in the CNS. This article, however, attempts to focus on the significant advances by Hoebel and others in dissecting out behavioral components of distinct aversive states and in understanding the neurobiology of aversion and the link between aversive states and addictive behaviors. Reward and aversion are not necessarily dichotomous and may reflect an affective continuum contingent upon environmental conditions. Descriptive and mechanistic studies pioneered by Bart Hoebel have demonstrated that the shift in the reward-aversion spectrum may be, in part, a result of changes in central dopamine/acetylcholine ratio, particularly in the nucleus accumbens. The path to aversion appears to include a specific neurochemical signature: reduced dopamine release and increased acetylcholine release in "reward centers" of the brain. Opioid receptors may have a neuromodulatory role on both of these neurotransmitters.
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Affiliation(s)
- Erin N Umberg
- Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, United States
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