Irritable bowel syndrome (IBS) is a common condition characterized by abdominal pain and altered bowel habits, affecting around 11% of individuals globally. It is linked to dysregulation of the brain-gut axis, with altered activity and connectivity in various brain regions. IBS patients often have psychiatric comorbidities like anxiety, or obsessive-compulsive disorder (OCD). Deep brain stimulation (DBS) is an established treatment option for severe, therapy-refractory OCD. It has been suggested that DBS for OCD could also have a beneficial effect on accompanying IBS-symptoms.

Nine patients with treatment-refractory OCD who underwent DBS in the bed nucleus striae terminalis (BNST) have been included in this study (4 males, 5 females, mean age: 39.1 ± 11.5 years). Patients were examined with the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) as well as the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) both before the beginning of DBS as well as throughout several follow-up visits for 12 months following the start of DBS.

Three patients displayed clinically relevant levels of IBS-symptoms at baseline (GSRS-IBS scores at or beyond 32). All of those three patients showed a reduction of the GSRS-IBS score at the last follow-up (12-40%). For the other 6 patients, 5 of them showed also a reduction of the GSRS-IBS compared to the score at baseline. The mean score for all patients showed a descriptive trend toward score reduction throughout the study period and until the last follow up visit after 12 months. The mean Y-BOCS decreased from 31.11 at baseline to 16.50 at the last follow-up. Out of the 9 patients, 7 (78%) were considered responders with Y-BOCS scores decreasing between 37% to 74%. Moderate-to-large correlations between both scales could be observed at both the 9-month and the 12-month follow-up visit. However, none of these associations was statistically significant.

In this study, we found alleviation of IBS symptoms after DBS of the BNST, along with improvement in OCD symptoms. Future research using larger sample sizes should address whether the reductions are tied to the improvement of OCD symptoms or if DBS exerts positive effects on IBS independently of OCD symptoms.

Randomized clinical trials (RCTs) are considered the gold standard for evaluating the efficacy of healthcare interventions. However, conflicts of interest (COIs) can compromise the scientific integrity in these trials. This study characterized COIs in RCTs on spinal cord stimulation for chronic pain, focusing on the prevalence, disclosure, and monetary value of COIs.

This cross-sectional study analyzed RCTs published from January 1, 2013 to July 27, 2023. Primary outcomes included the presence, disclosure, and monetary value of COIs, while secondary outcomes assessed the presence of direct/indirect COIs, sponsor access to data, and associations between COIs and select variables, including journal impact factor, publication year, and study outcomes.

Of 38 RCTs, 30 (78.9%) reported COIs. On average, 35.6% of authors per RCT had at least one COI, with a mean of 0.7 COIs per author. The mean annual monetary value of COIs was US$41,157.83 per author per RCT. 29 RCTs (76.3%) had undisclosed COIs, with an average of 24.2% of authors per RCT having undisclosed COIs. Sponsor access to data was reported in 67.6% of RCTs. No associations were observed between the mean percentage of authors with COIs and the monetary value of COIs and select dependent variables (impact factor, publication year, and study outcomes).

A substantial majority of RCTs reported COIs with many authors having undisclosed conflicts, highlighting the need for stringent COI disclosure guidelines to maintain research integrity. Expanding COI registry systems globally and increasing non-industry funding are crucial steps toward enhancing transparency and reducing biases in medical research.

Treatment options for abdominal pain in IBS are inadequate. TEA was reported effective treatment of disorders of gut-brain interaction but its mechanism of action and optimal delivery method for treating pain in IBS are unknown. This study aims to determine the most effective TEA parameter and location to treat abdominal pain in patients with IBS-Constipation and delineate the effect of TEA on rectal sensation and autonomic function.

Nineteen IBS-C patients underwent TEA at acupoints ST36 (leg), PC6 (wrist), or sham-acupoint. Each patient was studied in five randomized sessions on separate days: (1) TEA/ST36-100 Hz; (2) TEA/ST36-25 Hz; (3) TEA/PC6-100 Hz; (4) TEA/PC6-25 Hz; (5) TEA/Sham-25 Hz. In each session, barostat-guided rectal distention (RD) was performed before and after TEA. Patients graded the RD-induced pain and recorded three rectal sensation thresholds. A heart rate variability (HRV) signal was derived from the electrocardiogram for autonomic function assessment.

Studied patients were predominantly female, young, and Caucasian. Compared with baseline, patients treated with TEA/ST36-100 Hz had significantly decreased pain scores at RD pressure-points 20-50 mmHg (p < 0.04). The average pain reduction was 40%. Post-treatment scores did not change significantly with other TEA modalities except with sham-TEA (lesser degree compared to ST36-100 Hz, p = 0.04). TEA/ST36-100, but not other modalities, increased the rectal sensation threshold (first sensation: p = 0.007; urge to defecate: p < 0.026). TEA/ST36-100 Hz was the only treatment that significantly decreased sympathetic activity and increased parasympathetic activity with and without RD (p < 0.04).

TEA at ST36-100 Hz is superior stimulation point/parameter, compared to TEA at PC-6/sham-TEA, to reduce rectal distension-induced pain in IBS-C patients. This therapeutic effect appears to be mediated through rectal hypersensitivity reduction and autonomic function modulation.

Background and Objectives: This review systematically evaluates the potential of electrical neuromodulation techniques-vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)-as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's Disease (CD). It aims to synthesize current evidence on the efficacy and safety of these modalities, addressing the significant burden of IBD on patient quality of life and the limitations of existing pharmacological therapies. Materials and Methods: We conducted a comprehensive analysis of studies from PubMed, focusing on research published between 1978 and 2024. The review included animal models and clinical trials investigating the mechanisms, effectiveness, and safety of VNS, SNS, and TNS in IBD management. Special attention was given to the modulation of inflammatory responses and its impact on gastrointestinal motility and functional gastrointestinal disorders associated with IBD. Results: Preliminary findings suggest that VNS, SNS, and TNS can significantly reduce inflammatory markers and improve symptoms in IBD patients. These techniques also show potential in treating related gastrointestinal disorders during IBD remission phases. However, the specific mechanisms underlying these benefits remain to be fully elucidated, and there is considerable variability in treatment parameters. Conclusions: Electrical neuromodulation holds promise as a novel therapeutic avenue for IBD, offering an alternative to patients who do not respond to traditional treatments or experience adverse effects. The review highlights the need for further rigorous studies to optimize stimulation parameters, understand long-term outcomes, and integrate neuromodulation effectively into IBD treatment protocols.

A male in his mid-50s with a history of cerebral palsy was referred to the neurosurgical department for the management of chronic abdominal visceral pain after nine years of suffering. He had refractory constipation in his youth. Following a permanent colostomy for intestinal obstruction, visceral pain emerged over the right abdominal area, which became refractory to medication. Spinal cord stimulation (SCS) was performed with a pair of electrodes placed over the right mid-dorsal column between the T11-12 segments. Low-frequency stimuli with enough intensity to induce abdominal twitching reduced pain and relieved constipation for at least one year's follow-up. As the effects were strong and persistent, our findings suggest a novel neuromodulation therapy for chronic constipation. However, clinicians should be aware of the potential risk of unwanted gastrointestinal symptoms when thoracic SCS is performed.

Visceral pain, characterized by pain that is diffuse and challenging to localize, occurs frequently and is difficult to treat. In cases where the pain becomes intractable despite optimal medical management, it can affect patients' Quality of Life (QoL). Spinal Cord Stimulation (SCS) has emerged as a potential solution for intractable visceral pain.

In this narrative review, we collected all evidence regarding the efficacy of SCS for visceral pain across various underlying conditions.

A comprehensive literature search was conducted in PubMed, Embase, and Web of Science in which articles published from October 1st, 1963 up to March 7th, 2023 were identified.

Seventy articles were included in this review of which most were retrospective cohort studies, case series and case reports. The studies, often with a small number of participants, reported on SCS for chronic pancreatitis, anorectal pain and bowel disorders, gynaecological diagnoses, visceral pelvic pain, urological disorders and finally general visceral pain. They found positive effects on pain and/or symptom relief, opioid consumption, anxiety and depression and QoL. Complications occurred frequently but were often minor and reversible.

Better screening and selection criteria need to be established to optimally evaluate eligible patients who might benefit from SCS. A positive outcome of a sympathetic nerve block appears to be a potential indicator of SCS effectiveness. Additionally, women receiving SCS for endometriosis had a better outcome compared to other indications. Finally, SCS could also relief functional symptoms such as voiding problems and gastroparesis. Complications could often be resolved with revision surgery. Since SCS is expensive and not always covered by standard health insurance, the incorporation of cost-analyses is recommended. In order to establish a comprehensive treatment plan, including selection criteria for SCS, rigorous prospective, possibly randomized and controlled studies that are diagnosis-oriented, with substantial follow-up and adequate sample sizes, are needed.

Neuropathic pain is generally defined as a non-physiological pain experience caused by damage to the nervous system. It can occur spontaneously, as a reaction to a given stimulus, or independently of its action, leading to unusual pain sensations usually referred to as firing, burning or throbbing. In the course of spine disorders, pain symptoms commonly occur. According to available epidemiological studies, a neuropathic component of pain is often present in patients with spinal diseases, with a frequency ranging from 36% to 55% of patients. Distinguishing between chronic nociceptive pain and neuropathic pain very often remains a challenge. Consequently, neuropathic pain is often underdiagnosed in patients with spinal diseases. In reference to current guidelines for the treatment of neuropathic pain, gabapentin, serotonin and norepinephrine reuptake inhibitors and tricyclic antidepressants constitute first-line therapeutic agents. However, long-term pharmacologic treatment often leads to developing tolerance and resistance to used medications. Therefore, in recent years, a plethora of therapeutic methods for neuropathic pain have been developed and investigated to improve clinical outcomes. In this review, we briefly summarized current knowledge about the pathophysiology and diagnosis of neuropathic pain. Moreover, we described the most effective treatment approaches for neuropathic pain and discussed their relevance in the treatment of spinal pain.

Inflammatory bowel disease (IBD) is an inflammatory disease of the gastrointestinal (GI) tract. It has financial and quality of life impact on patients. Although there has been a significant advancement in treatments, a considerable number of patients do not respond to it or have severe side effects. Therapeutic approaches such as electrical neuromodulation are being investigated to provide alternate options. Although bioelectric neuromodulation technology has evolved significantly in the last decade, sacral nerve stimulation (SNS) for fecal incontinence remains the only neuromodulation protocol commonly utilized use for GI disease. For IBD treatment, several electrical neuromodulation techniques have been studied, such as vagus NS, SNS, and tibial NS. Several animal and clinical experiments were conducted to study the effectiveness, with encouraging results. The precise underlying mechanisms of action for electrical neuromodulation are unclear, but this modality appears to be promising. Randomized control trials are required to investigate the efficacy of intrinsic processes. In this review, we will discuss the electrical modulation therapy for the IBD and the data pertaining to it.

Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity.

To evaluate the efficacy, effectiveness, adverse events, and cost-effectiveness of implanted spinal neuromodulation interventions for people with chronic pain.

We searched CENTRAL, MEDLINE Ovid, Embase Ovid, Web of Science (ISI), Health Technology Assessments, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry from inception to September 2021 without language restrictions, searched the reference lists of included studies and contacted experts in the field.

We included randomised controlled trials (RCTs) comparing SNMD interventions with placebo (sham) stimulation, no treatment or usual care; or comparing SNMD interventions + another treatment versus that treatment alone. We included participants ≥ 18 years old with non-cancer and non-ischaemic pain of longer than three months duration. Primary outcomes were pain intensity and adverse events. Secondary outcomes were disability, analgesic medication use, health-related quality of life (HRQoL) and health economic outcomes.

Two review authors independently screened database searches to determine inclusion, extracted data and evaluated risk of bias for prespecified results using the Risk of Bias 2.0 tool. Outcomes were evaluated at short- (≤ one month), medium- four to eight months) and long-term (≥12 months). Where possible we conducted meta-analyses. We used the GRADE system to assess the certainty of evidence.

We included 15 unique published studies that randomised 908 participants, and 20 unique ongoing studies. All studies evaluated SCS. We found no eligible published studies of DRGS and no studies comparing SCS with no treatment or usual care. We rated all results evaluated as being at high risk of bias overall. For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as low or very low, downgraded due to limitations of studies, imprecision and in some cases, inconsistency. Active stimulation versus placebo SCS versus placebo (sham) Results were only available at short-term follow-up for this comparison. Pain intensity Six studies (N = 164) demonstrated a small effect in favour of SCS at short-term follow-up (0 to 100 scale, higher scores = worse pain, mean difference (MD) -8.73, 95% confidence interval (CI) -15.67 to -1.78, very low certainty). The point estimate falls below our predetermined threshold for a clinically important effect (≥10 points). No studies reported the proportion of participants experiencing 30% or 50% pain relief for this comparison. Adverse events (AEs) The quality and inconsistency of adverse event reporting in these studies precluded formal analysis. Active stimulation + other intervention versus other intervention alone SCS + other intervention versus other intervention alone (open-label studies) Pain intensity Mean difference Three studies (N = 303) demonstrated a potentially clinically important mean difference in favour of SCS of -37.41 at short term (95% CI -46.39 to -28.42, very low certainty), and medium-term follow-up (5 studies, 635 participants, MD -31.22 95% CI -47.34 to -15.10 low-certainty), and no clear evidence for an effect of SCS at long-term follow-up (1 study, 44 participants, MD -7 (95% CI -24.76 to 10.76, very low-certainty). Proportion of participants reporting ≥50% pain relief We found an effect in favour of SCS at short-term (2 studies, N = 249, RR 15.90, 95% CI 6.70 to 37.74, I2 0% ; risk difference (RD) 0.65 (95% CI 0.57 to 0.74, very low certainty), medium term (5 studies, N = 597, RR 7.08, 95 %CI 3.40 to 14.71, I2 = 43%; RD 0.43, 95% CI 0.14 to 0.73, low-certainty evidence), and long term (1 study, N = 87, RR 15.15, 95% CI 2.11 to 108.91 ; RD 0.35, 95% CI 0.2 to 0.49, very low certainty) follow-up. Adverse events (AEs) Device related No studies specifically reported  device-related adverse events at short-term follow-up. At medium-term follow-up, the incidence of lead failure/displacement (3 studies N = 330) ranged from 0.9 to 14% (RD 0.04, 95% CI -0.04 to 0.11, I2 64%, very low certainty). The incidence of infection (4 studies, N = 548) ranged from 3 to 7% (RD 0.04, 95%CI 0.01, 0.07, I2 0%, very low certainty). The incidence of reoperation/reimplantation (4 studies, N =5 48) ranged from 2% to 31% (RD 0.11, 95% CI 0.02 to 0.21, I2 86%, very low certainty). One study (N = 44) reported a 55% incidence of lead failure/displacement (RD 0.55, 95% CI 0.35, 0 to 75, very low certainty), and a 94% incidence of reoperation/reimplantation (RD 0.94, 95% CI 0.80 to 1.07, very low certainty) at five-year follow-up. No studies provided data on infection rates at long-term follow-up. We found reports of some serious adverse events as a result of the intervention. These included autonomic neuropathy, prolonged hospitalisation, prolonged monoparesis, pulmonary oedema, wound infection, device extrusion and one death resulting from subdural haematoma. Other No studies reported the incidence of other adverse events at short-term follow-up. We found no clear evidence of a difference in otherAEs at medium-term (2 studies, N = 278, RD -0.05, 95% CI -0.16 to 0.06, I2 0%) or long term (1 study, N = 100, RD -0.17, 95% CI -0.37 to 0.02) follow-up. Very limited evidence suggested that SCS increases healthcare costs. It was not clear whether SCS was cost-effective.

We found very low-certainty evidence that SCS may not provide clinically important benefits on pain intensity compared to placebo stimulation. We found low- to very low-certainty evidence that SNMD interventions may provide clinically important benefits for pain intensity when added to conventional medical management or physical therapy. SCS is associated with complications including infection, electrode lead failure/migration and a need for reoperation/re-implantation. The level of certainty regarding the size of those risks is very low. SNMD may lead to serious adverse events, including death. We found no evidence to support or refute the use of DRGS for chronic pain.

Chronic abdominal pain (CAP) can arise from multiple conditions, including inflammatory disorders, trauma because of injury or surgery, or structural or functional causes. This prospective, single-arm study was designed to evaluate the safety and efficacy of 10-kHz spinal cord stimulation (SCS) in patients with intractable CAP over a 12-month follow-up period.

Subjects with CAP who had been refractory to conventional medical treatment for at least 3 months resulting in self-reported pain scores of ≥5 cm on a 10-cm visual analog scale were enrolled at 4 centers in the United States. Study subjects underwent a trial stimulation lasting up to 14 days with epidural leads implanted from the vertebral levels T4 through T8. Subjects who had ≥40% pain relief during the trial stimulation period were implanted with a Senza system (Nevro Corp., Redwood City, CA) and followed up to 12 months after surgery.

Twenty-three of 24 subjects (95.8%) had a successful trial stimulation and proceeded to a permanent implant. After 12 months of treatment with 10-kHz SCS, 78.3% of subjects were responders (pain relief of ≥50%) and 14 of 22 subjects (63.6%) were remitters (sustained ≤3.0-cm visual analog scale scores). Secondary outcomes, including assessments of disability, mental and physical well-being, sleep quality, perception of improvement, and satisfaction, showed that 10-kHz SCS greatly improved the quality of life of patients with CAP. Observationally, most subjects also reported concurrent reduction or resolution of nausea and/or vomiting.

10-kHz SCS can provide durable pain relief and improve the quality of life in patients with CAP.

Spinal cord stimulation (SCS) is a neuromodulation technology widely used in the treatment of intractable chronic pain syndromes. SCS is now being applied more broadly as a possible therapy for a range of indications, including neurological, cardiac, and gastrointestinal disorders. Ongoing research in this field is critical in order to gain further insights into the mechanisms of SCS, determine its role in new indications, and refine programming techniques for the optimization of therapeutic outcomes.

To assess the state of SCS-related human research by cataloging and summarizing clinical trials that have been recently completed or are currently underway in this field.

A search was conducted for clinical trials pertaining to SCS using the ClinicalTrials.gov database. Trials were analyzed to generate a detailed overview of ongoing SCS-related research. Specifically, trials were categorized by intervention, trial start date, study completion status, clinical phase, projected subject enrollment, condition, country of origin, device manufacturer, funding source, and study topic.

In total, 212 relevant clinical trials were identified. 175 trials (82.5%) involved invasive SCS, while the remaining 37 trials (17.5%) used noninvasive forms of spinal stimulation. Most trials examined the efficacy of SCS for chronic pain syndromes or new indications, while others assessed different stimulation parameters. The studies spanned >27 different disorders, with almost 20% of trials pertaining to conditions other than chronic pain syndromes. The majority of SCS trials were US-based (55.7% of studies), but many countries (e.g., Belgium and UK) are becoming increasingly active. The ratio of investigator-sponsored to industry-sponsored trials was 2:1. Emphasizing the need to optimize therapeutic outcomes of SCS, one-quarter of trials predominantly focused on the assessment of alternative stimulation parameters such as burst or high-frequency stimulation.

A large number of clinical trials of SCS are underway. Improvements in the treatment of pain and novel indications for SCS constitute the majority of studies. This overview of SCS-related clinical trials provides a window into future new indications, novel stimulation techniques, and a heightened understanding of the mechanisms of action.

Auricular neurostimulation therapy, in which a noninvasive device delivers percutaneous electrical nerve field stimulation (PENFS) to the external ear, is effective in pediatric patients with functional abdominal pain disorders. Preclinical studies showed that PENFS modulates central pain pathways and attenuates visceral hyperalgesia. We evaluated the efficacy of PENFS in adolescents with irritable bowel syndrome (IBS).

We analyzed data from pediatric patients with IBS who participated in a double-blind trial at a tertiary care gastroenterology clinic from June 2015 through November 2016. Patients were randomly assigned to groups that received PENFS (n = 27; median age, 15.3 y; 24 female) or a sham stimulation (n = 23; median age, 15.6 y; 21 female), 5 days/week for 4 weeks. The primary endpoint was number of patients with a reduction of 30% or more in worst abdominal pain severity after 3 weeks. Secondary endpoints were reduction in composite abdominal pain severity score, reduction in usual abdominal pain severity, and improvement in global symptom based on a symptom response scale (-7 to +7; 0 = no change) after 3 weeks.

Reductions of 30% or more in worst abdominal pain were observed in 59% of patients who received PENFS vs 26% of patients who received the sham stimulation (P = .024). The patients who received PENFS had a composite pain median score of 7.5 (interquartile range [IQR], 3.6-14.4) vs 14.4 for the sham group (IQR, 4.5-39.2) (P = .026) and a usual pain median score of 3.0 (IQR, 3.0-5.0) vs 5.0 in the sham group (IQR, 3.0-7.0) (P = .029). A symptom response scale score of 2 or more was observed in 82% of patients who received PENFS vs 26% of patients in the sham group (P ≤ .001). No significant side effects were reported.

Auricular neurostimulation reduces abdominal pain scores and improves overall wellbeing in adolescents with IBS. PENFS is a noninvasive treatment option for pediatric patients with functional bowel disorders. ClinicalTrials.gov no: NCT02367729.

Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the digestive tract that is often debilitating. It affects patients' quality of life and imposes a financial burden. Despite advances in treatment with medications such as biologics, a large proportion of patients do not respond to medical therapy or develop adverse events. Therefore, alternative treatment options such as electrical neuromodulation are currently being investigated. Electrical neuromodulation, also called bioelectronic medicine, is emerging as a potential new treatment for IBD. Over the past decade, advancements have been made in electrical neuromodulation. A number of electrical neuromodulation methods, such as vagus nerve stimulation, sacral nerve stimulation, and tibial nerve stimulation, have been tested to treat IBD. A series of animal and clinical trials have been performed to evaluate efficacy with promising results. Although the exact underlying mechanisms of action for electrical neuromodulation remain to be explored, this modality is promising. Further randomized controlled trials and basic experiments are needed to investigate efficacy and clarify intrinsic mechanisms.

This systematic review assessed design characteristics and reporting quality of published randomized clinical trials of spinal cord stimulation (SCS) for treatment of pain in adults and adolescents. The study protocol was registered with PROSPERO (CRD42018090412). Relevant articles were identified by searching the following databases through December 31, 2018: MEDLINE, Embase, WikiStim, The Cochrane Database of Systematic Reviews, and The Cochrane Central Register of Controlled Trials. Forty-six studies were included. Eighty-seven percent of articles identified a pain-related primary outcome. Secondary outcomes included physical functioning, health-related quality of life, and reductions in opioid use. Nineteen of the 46 studies prespecified adverse events as an outcome, with 4 assessing them as a primary outcome. Eleven studies stated that they blinded participants. Of these, only 5 were assessed as being adequately blinded. The number of participants enrolled was generally low (median 38) and study durations were short (median 12 weeks), particularly in studies of angina. Fifteen studies employed an intention-to-treat analysis, of which only seven specified a method to accommodate missing data. Review of these studies identified deficiencies in both reporting and methodology. The review's findings suggest areas for improving the design of future studies and increasing transparency of reporting. PERSPECTIVE: This article presents a systematic review of research methods and reporting quality of randomized clinical trials of SCS for the treatment of various pain complaints. The review identifies deficiencies in both methodology and reporting, which may inform the design of future studies and improve reporting standards.

The recent availability of paraesthesia/sensation free spinal cord stimulation (SCS) modalities allow the design of clinical trials of SCS using placebo/sham controls and blinding of patients, clinicians, and researchers. The aims of this study were to: 1) systematically review the current evidence base of randomized controlled trials (RCTs) of SCS placebo/sham trials and 2) to undertake a methodological critique of their methods. Based on this critique, we developed a checklist for the design and reporting of future RCTs of SCS.

Electronic data bases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. RCTs with only an active comparator arm were excluded. The results are presented as a narrative synthesis.

Searches identified 12 eligible RCTs. SCS modalities included paraesthesia stimulation, subthreshold, burst, and high-frequency SCS and were mainly conducted in patients with failed back surgery syndrome, complex regional pain syndrome, and refractory angina. The quality and transparency of reporting of the methods of placebo stimulation, blinding of patients, clinicians, and researchers varied markedly across studies.

To date the methods of placebo/sham control and blinding in RCTs have been poorly reported, leading to concerns about the validity and replicability of the findings. Important aspects that need to be clearly reported in the design of placebo-/sham-controlled RCTs of SCS include the transparent reporting of stimulation programming parameters, patient position during perception threshold measurement, management of the patient handheld programmer, frequency of recharging, and assessment of the fidelity of blinding.

Development of safe and effective therapies for paediatric abdominal pain-related functional gastrointestinal disorders is needed. A non-invasive, US Food and Drug Administration-cleared device (Neuro-Stim, Innovative Health Solutions, IN, USA) delivers percutaneous electrical nerve field stimulation (PENFS) in the external ear to modulate central pain pathways. In this study, we evaluated the efficacy of PENFS in adolescents with abdominal pain-related functional gastrointestinal disorders.

In this randomised, sham-controlled trial, we enrolled adolescents (aged 11-18 years) who met Rome III criteria for abdominal pain-related functional gastrointestinal disorders from a single US outpatient gastroenterology clinic. Patients were randomly assigned (1:1) with a computer-generated randomisation scheme to active treatment or sham (no electrical charge) for 4 weeks. Patients were stratified by sex and presence or absence of nausea. Allocation was concealed from participants, caregivers, and the research team. The primary efficacy endpoint was change in abdominal pain scores. We measured improvement in worst abdominal pain and composite pain score using the Pain Frequency-Severity-Duration (PFSD) scale. Participants with less than 1 week of data and those with organic disease identified after enrolment were excluded from the modified intention-to-treat population. This trial has been completed and is registered with ClinicalTrials.gov, number NCT02367729.

Between June 18, 2015, and Nov 17, 2016, 115 children with abdominal pain-related functional gastrointestinal disorders were enrolled and assigned to either PENFS (n=60) with an active device or sham (n=55). After exclusion of patients who discontinued treatment (n=1 in the PENFS group; n=7 in the sham group) and those who were excluded after randomisation because they had organic disease (n=2 in the PENFS group; n=1 in the sham group), 57 patients in the PENFS group and 47 patients in the sham group were included in the primary analysis. Patients in the PENFS group had greater reduction in worst pain compared with sham after 3 weeks of treatment (PENFS: median score 5·0 [IQR 4·0-7·0]; sham: 7·0 [5·0-9·0]; least square means estimate of change in worse pain 2·15 [95% CI 1·37-2·93], p<0·0001). Effects were sustained for an extended period (median follow-up 9·2 weeks [IQR 6·4-13·4]) in the PENFS group: median 8·0 (IQR 7·0-9·0) at baseline to 6·0 (5·0-8·0) at follow-up versus sham: 7·5 (6·0-9·0) at baseline to 7·0 (5·0-8·0) at follow-up (p<0·0001). Median PFSD composite scores also decreased significantly in the PENFS group (from 24·5 [IQR 16·8-33.3] to 8·4 [3·2-16·2]) compared with sham (from 22·8 [IQR 8·4-38·2] to 15·2 [4·4-36·8]) with a mean decrease of 11·48 (95% CI 6·63-16·32; p<0·0001) after 3 weeks. These effects were sustained at extended follow-up in the PENFS group: median 24·5 (IQR 16·8-33·3) at baseline to 12 (3·6-22·5) at follow-up, compared with sham: 22·8 (8·4-38·2) at baseline to 16·8 (4·8-33·6) at follow-up (p=0·018). Ten patients reported side-effects (three of whom discontinued the study): ear discomfort (n=6; three in the PENFS group, three in the sham group), adhesive allergy (n=3; one in the PENFS group, two in the sham group), and syncope due to needle phobia (n=1; in the sham group). There were no serious adverse events.

Our results show that PENFS with Neuro-Stim has sustained efficacy for abdominal pain-related functional gastrointestinal disorders in adolescents. This safe and effective approach expands treatment options and should be considered as a non-pharmacological alternative for these disorders.

American Neurogastroenterology and Motility Society.