Cross-sectional experimental assessment of pain modulation as part of multidimensional profiling of people with cervicogenic headache: protocol for a feasibility study.

BACKGROUND: An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism. For individuals with cervicogenic headache (CeH), the characteristics of such profiles were never investigated. However, the individual nature of experiencing pain demands profiling within a multidimensional framework including psychosocial lifestyle characteristics. The objective of the current protocol is to assess the pain modulation profile, which includes psychosocial lifestyle characteristics among people with CeH. METHODS AND ANALYSIS: A protocol is described to map pain modulation profiles in people with CeH. A cross-sectional non-randomised experimental design will be used to assess feasibility of mapping these profiles. The pain modulation profile is composed based on results on the Depression, Anxiety, Stress Scale, Pittsburgh Sleep Quality Index, Headache Impact Test and on responses to temporal summation of pain (pinprick), conditioned pain modulation and widespread hyperalgesia (mechanical pressure pain threshold and cuff algometry). Primary analyses will report results relating to outcomes on feasibility. Secondary analyses will involve an analysis of proportions (%) of the different psychosocial lifestyle profiles and pain profiles. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee Research UZ/KU Leuven (Registration number B3222024001434) on 30 May 2024. Results will be published in peer-reviewed journals, at scientific conferences and, through press releases. Protocol V.3. protocol date: 3 June 2024.

Pancreatic quantitative sensory testing to predict treatment response of endoscopic therapy or surgery for painful chronic pancreatitis with pancreatic duct obstruction: study protocol for an observational clinical trial.

INTRODUCTION: Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP. METHODS AND ANALYSIS: This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction. PRIMARY OUTCOME: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment. ETHICS AND DISSEMINATION: The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies. TRIAL REGISTRATION NUMBER: NCT04996628.

Perineural injections of incobotulinumtoxin-A for diabetic neuropathic pain of the lower extremities: protocol for a phase II, single-centre, double-blind, randomised, placebo-controlled trial (the PINBOT study).

INTRODUCTION: Diabetic neuropathic pain (DNP) is a debilitating complication affecting 15-20% of people with diabetes and is a predictor of depression, poor sleep and decreased quality of life. Current pharmacological treatments are often insufficient and have significant side-effects. Subcutaneous or intradermal botulinumtoxin-A (BonT-A) is an effective and safe treatment for neuropathic pain but is limited by the need to cover the entire affected area with injections. For large cutaneous areas, infiltration of the sensory nerve supply with BonT-A could provide similar effects, with a single injection. We aim to investigate the safety, efficacy, and effects on quality of life, physical activity, depressive symptoms and activities of daily living of perineural injections of BonT-A in patients with DNP of both lower extremities. METHODS: This study is a double-blind, randomised, placebo-controlled clinical trial. 80 participants with moderate to severe DNP of both legs will be randomised 1:1 to receive injections of either 100 units incobotulinumtoxin-A or a saline placebo around each distal sciatic nerve for two cycles of 12 weeks. Average daily pain scores will be recorded once a day from 1 week prior to the first treatment and through the entire study period. Primary outcomes are differences between groups in daily and weekly mean pain scores. Secondary outcomes are levels of physical activity, depression scores, health-related quality of life, activities of daily living, sensory profiles and motor function, recorded at baseline, 4, 12, 16 and 24 weeks. The use of rescue medication and adverse events will be recorded throughout the study period. ETHICS AND DISSEMINATION: The study is approved by the Danish Committee on Health Research Ethics and the Danish Medicines Agency. EU-Clinical Trial Information System (EU: 2022-500727-68-01), clinicaltrials.gov (ID: NCT05623111). Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05623111.

Cannabis for medical use versus opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised clinical trials.

OBJECTIVE: The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021. STUDY SELECTION: Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings. RESULTS: Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) -1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI -0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI -4.72 to 5.59). CONCLUSIONS: Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain. PROSPERO REGISTRATION NUMBER: CRD42020185184.

Effectiveness of transcranial direct current stimulation (tDCS) as adjunctive treatment for chronic headache in adults with clinically stable systemic lupus erythematosus (SHADE): a randomised double-blind multiarm sham controlled clinical trial.

BACKGROUND: Chronic headache is a 'silent' neuropsychiatric systemic lupus erythematosus symptom with heterogeneous prevalence, potentially reaching 54.4%. It may reduce quality of life by increasing the likelihood of depression and sleep disturbance. While pharmacotherapy remains the first-line treatment, the current management is still challenging and needs other non-invasive modalities. An effective, tolerable and disease-specific treatment modality including transcranial direct current stimulation (tDCS) is considered to reduce the frequency of chronic headaches, including in SLE. Until recently, there was no standard protocol for tDCS in treating headaches. METHODS AND ANALYSIS: SHADE is a single-centre randomised double-blind multiarm sham-controlled trial for adults with clinically stable SLE, chronic headaches and without history of traumatic brain injury, brain infection, stroke or brain tumour. Random allocation is conducted to 88 subjects into 3 treatment groups (administration at primary motor, primary sensory and dorsolateral prefrontal cortex) and control group in 1:1:1:1 ratio. The primary endpoint is reduced number of headache days after adjunctive tDCS. The secondary endpoints are reduced headache intensity, increased quality of life, increased sleep quality, decreased depression and reduced analgesics use. The outcome is measured monthly until 3-month postintervention using headache diary, 36-Item Short Form Survey, Chronic Headache Quality of Life Questionnaire, Pittsburgh Sleep Quality Index and Mini International Neuropsychiatry Interview version 10 (MINI ICD 10). Intention-to-treat analysis will be performed to determine the best tDCS electrode placement. ETHICS AND DISSEMINATION: Ethical approval had been obtained from the local Institutional Review Board of Faculty of Medicine Universitas Indonesia. Results will be published through scientific relevant peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05613582.

Feasibility interventional study investigating PAIN in neurorehabilitation through wearabLE SensorS (PAINLESS): a study protocol.

INTRODUCTION: Millions of people survive injuries to the central or peripheral nervous system for which neurorehabilitation is required. In addition to the physical and cognitive impairments, many neurorehabilitation patients experience pain, often not widely recognised and inadequately treated. This is particularly true for multiple sclerosis (MS) patients, for whom pain is one of the most common symptoms. In clinical practice, pain assessment is usually conducted based on a subjective estimate. This approach can lead to inaccurate evaluations due to the influence of numerous factors, including emotional or cognitive aspects. To date, no objective and simple to use clinical methods allow objective quantification of pain and the diagnostic differentiation between the two main types of pain (nociceptive vs neuropathic). Wearable technologies and artificial intelligence (AI) have the potential to bridge this gap by continuously monitoring patients' health parameters and extracting meaningful information from them. Therefore, we propose to develop a new automatic AI-powered tool to assess pain and its characteristics during neurorehabilitation treatments using physiological signals collected by wearable sensors. METHODS AND ANALYSIS: We aim to recruit 15 participants suffering from MS undergoing physiotherapy treatment. During the study, participants will wear a wristband for three consecutive days and be monitored before and after their physiotherapy sessions. Measurement of traditionally used pain assessment questionnaires and scales (ie, painDETECT, Doleur Neuropathique 4 Questions, EuroQoL-5-dimension-3-level) and physiological signals (photoplethysmography, electrodermal activity, skin temperature, accelerometer data) will be collected. Relevant parameters from physiological signals will be identified, and AI algorithms will be used to develop automatic classification methods. ETHICS AND DISSEMINATION: The study has been approved by the local Ethical Committee (285-2022-SPER-AUSLBO). Participants are required to provide written informed consent. The results will be disseminated through contributions to international conferences and scientific journals, and they will also be included in a doctoral dissertation. TRIAL REGISTRATION NUMBER: NCT05747040.

Efficacy of transcutaneous auricular vagus nerve stimulation on radiotherapy-related neuropathic pain in patients with head and neck cancers (RELAX): protocol for a multicentre, randomised, double-blind, sham-controlled trial.

INTRODUCTION: Radiotherapy-related neuropathic pain (RRNP) is one of the most distressing complications after radiotherapy for head and neck cancers. Drug therapy is not sufficiently effective and has limitations in terms of dose titration period and side effects. Transcutaneous auricular vagus nerve stimulation (taVNS), which stimulates the auricular branches of the vagus nerve through electrical impulses, has been proven to have analgesic effects in certain diseases. However, it is unknown whether taVNS can relieve RRNP. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blind, parallel, sham-controlled trial. We will include adult patients newly diagnosed with neuropathic pain after radiotherapy for head and neck cancers. One hundred and sixteen individuals will be recruited and randomly assigned in a 1:1 ratio to receive taVNS or sham stimulation. The interventions will last for 7 days, twice daily for 30 min each. The primary efficacy outcome is pain reduction on day 7. The secondary outcomes are changes in functional interference, psychological distress, fatigue, quality of life and serum inflammatory factors. The study may provide a new early intervention strategy for RRNP among patients with head and neck cancers. ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethics Committee of Sun Yat-sen University (SYSKY-2022-109-01) and will be conducted in strict accordance with the Declaration of Helsinki. Ethical approvals will be obtained separately for all centres involved in the study. Study results will be published in peer-reviewed academic journals. The database of the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: NCT05543239.

Using remotely delivered Spring Forest Qigong™ to reduce neuropathic pain in adults with spinal cord injury: protocol of a quasi-experimental feasibility clinical trial.

BACKGROUND: About 69% of Americans living with spinal cord injury (SCI) suffer from long-term debilitating neuropathic pain, interfering with the quality of daily life. Neuropathic pain is refractory to many available treatments-some carrying a risk for opioid addiction-highlighting an urgent need for new treatments. In this study, we will test our hypothesis that Spring Forest Qigong™ will reduce SCI-related neuropathic pain by improving body awareness. We will determine whether remotely delivered Qigong is feasible and we will collect data on neuropathic pain, and other reported associations with pain such as spasms frequency and/or severity, functional performance, mood, and body awareness. METHODS: In this quasi-experimental pilot clinical trial study, adults with SCI will practice Qigong at home with a 45-min video, at least 3 × /week for 12 weeks. The Qigong practice includes movements with guided breathing and is individualized based on functional abilities, i.e., the participants follow along with the Qigong movements to the level of their ability, with guided breathing, and perform kinesthetic imagery by focusing on the feeling in the whole body as if doing the whole-body Qigong movement while standing. The highest, average, and lowest neuropathic pain ratings perceived in the prior week will be recorded weekly until the 6-week follow-up. The other outcomes will be collected at 5 time points: at baseline, midway during the Qigong intervention (6 weeks), after the Qigong intervention (12 weeks), after a 6-week and 1-year follow-up. Rate parameters for the feasibility markers will be estimated based on the participants who achieved each benchmark. DISCUSSION: The University of Minnesota (UMN)'s Institutional Review Board (IRB) approved the study (IRB #STUDY00011997). All participants will sign electronic informed consent on the secure UMN REDCap platform. The results will be presented at academic conferences and published in peer-reviewed publications. TRIAL REGISTRATION: ClinicalTrial.gov registration number: NCT04917107 , (this protocol paper refers to the substudy), first registered 6/8/2021.

Long-term efficacy and safety of erenumab in Japanese patients with episodic and chronic migraine: results from a 28-week open-label treatment period of a randomised trial.

OBJECTIVES: To evaluate the 1-year efficacy and safety of once-monthly erenumab 70 mg following a 24-week double-blind treatment period (DBTP) of a phase III randomised study of Japanese patients with episodic migraine (EM) or chronic migraine (CM). DESIGN: Multicentre open-label study. SETTING: A total of 41 centres in Japan. PARTICIPANTS: Patients completing the DBTP continued into the 28-week open-label treatment period (OLTP). 254 of 261 (97.3%) randomised patients continued into the OLTP; 244 (93.5%) completed treatment. INTERVENTIONS: Once-monthly subcutaneous erenumab 70 mg. MAIN OUTCOME MEASURES: Changes from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication treatment days (MSMD) reported via patient eDiary; proportion of ≥50% and ≥75% responders in MMD reduction from baseline; incidence and exposure-adjusted incidence of treatment-emergent adverse events (TEAEs). RESULTS: At week 24 of the DBTP, the mean (SE) change from baseline in MMD for the erenumab group was -3.8 (0.4) days (EM, -3.0 (0.4); CM, -5.2 (0.8)); in MSMD, -2.6 (0.4) days (EM, -2.1 (0.4); CM, -3.4 (0.7)). At the end of the OLTP (52 weeks postbaseline), the mean (SE) change from baseline in MMD was -4.7 (0.3) days (EM, -3.4 (0.3); CM, -6.9 (0.6)); in MSMD, -3.3 (0.3) days (EM, -2.4 (0.3); CM, -4.6 (0.5)). The proportion of ≥50% responders for MMD reduction in the erenumab group was 34.1% at week 24; 44.4% at week 52. The exposure-adjusted incidence of TEAEs was 219.7 per 100 patient-years during the OLTP (DBTP, 251.0 for the erenumab group). The most common TEAEs during the OLTP were nasopharyngitis, constipation and influenza. No new safety concerns were identified. CONCLUSIONS: Erenumab treatment was associated with reduced migraine frequency in Japanese patients with EM or CM for up to 1 year. Overall safety results from the OLTP were consistent with DBTP results. TRIAL REGISTRATION NUMBER: NCT03812224.

Impact of a 12-week olfactory training programme in women with migraine with aura: protocol for a double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Migraine is a leading cause of disability and suffering worldwide. However, conventional pharmacological migraine preventive therapies are often challenging and accompanied by adverse effects. Recently, structured odour exposure has shown to successfully increase pain thresholds in patients with chronic back pain. Despite the importance of the olfactory system in migraine, there are no studies investigating the impact of structured odour exposure in patients with migraine. METHODS AND ANALYSIS: This double-blind randomised placebo-controlled trial will be conducted at the Headache Clinic of the University Pain Center at TU Dresden, Germany and aims at investigating the impact of a 12-week structured exposure to odours in women with migraine. Fifty-four women between 18 and 55 years with migraine with aura will be recruited and randomised to training with odours and odourless training. The primary outcomes are mechanical and electrical pain thresholds. Secondary outcomes comprise olfactory threshold and the number of headache days. Other exploratory measurements are headache associated pain intensity, acute analgesic intake, symptoms of anxiety and depression, and quality of life. Additionally, this protocol assesses neuroanatomical and neurofunctional changes associated with the 12-week olfactory training. Data analysis will be executed on the basis of the general linear model considering repeated measurements. ETHICS AND DISSEMINATION: Ethical approvals were obtained from the Ethics Board of the TU Dresden (Protocol No. BO-EK-353082020). Participation will only be possible after written informed consent is provided. Findings will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00027399.

Exposure to hand-held vibrating tools and biomarkers of nerve injury in plasma: a population-based, observational study.

OBJECTIVES: To analyse potential biomarkers for vibration-induced nerve damage in a population-based, observational study. DESIGN: Prospective cohort study. SETTING: Malmö Diet Cancer Study (MDCS), Malmö, Sweden. PARTICIPANTS: In a subcohort of 3898 individuals (recruited 1991-1996) from MDCS (baseline examination in 28 449 individuals; collection of fasting blood samples in a cardiovascular subcohort of MDCS of 5540 subjects), neuropathy-relevant plasma biomarkers were analysed during follow-up after filling out questionnaires, including a question whether work involved hand-held vibrating tools, graded as 'not at all', 'some' or 'much'. PRIMARY OUTCOME MEASURES: The neuropathy-relevant plasma biomarkers vascular endothelial growth factor (VEGF)-A, VEGF-D, VEGF receptor 2, galanin, galectin-3, HSP27, ß-nerve growth factor, caspase-3, caspase-8, transforming growth factor-α and tumour necrosis factor were analysed. Data were analysed by conventional statistics (Kruskal-Wallis test; post hoc test Mann-Whitney U test; Bonferroni correction for multiple testing) and in a subanalysis for galanin using two linear regression models (unadjusted and adjusted). RESULTS: Among participants, 3361 of 3898 (86%) reported no work with hand-held vibrating tools, 351 of 3898 (9%) reported some and 186 of 3898 (5%) much work. There were more men and smokers in vibration-exposed groups. Galanin levels were higher after much vibration exposure (arbitrary units 5.16±0.71) compared with no vibration exposure (5.01±0.76; p=0.015) with no other observed differences. CONCLUSIONS: Higher plasma levels of galanin, possibly related to magnitude, frequency, acceleration and duration, as well as to severity of symptoms of vibration exposure, may be found in individuals working with hand-held vibrating tools.

Factors predicting the transition from acute to persistent pain in people with 'sciatica': the FORECAST longitudinal prognostic factor cohort study protocol.

INTRODUCTION: Sciatica is a common condition and is associated with higher levels of pain, disability, poorer quality of life, and increased use of health resources compared with low back pain alone. Although many patients recover, a third develop persistent sciatica symptoms. It remains unclear, why some patients develop persistent sciatica as none of the traditionally considered clinical parameters (eg, symptom severity, routine MRI) are consistent prognostic factors.The FORECAST study (factors predicting the transition from acute to persistent pain in people with 'sciatica') will take a different approach by exploring mechanism-based subgroups in patients with sciatica and investigate whether a mechanism-based approach can identify factors that predict pain persistence in patients with sciatica. METHODS AND ANALYSIS: We will perform a prospective longitudinal cohort study including 180 people with acute/subacute sciatica. N=168 healthy participants will provide normative data. A detailed set of variables will be assessed within 3 months after sciatica onset. This will include self-reported sensory and psychosocial profiles, quantitative sensory testing, blood inflammatory markers and advanced neuroimaging. We will determine outcome with the Sciatica Bothersomeness Index and a Numerical Pain Rating Scale for leg pain severity at 3 and 12 months.We will use principal component analysis followed by clustering methods to identify subgroups. Univariate associations and machine learning methods optimised for high dimensional small data sets will be used to identify the most powerful predictors and model selection/accuracy.The results will provide crucial information about the pathophysiological drivers of sciatica symptoms and may identify prognostic factors of pain persistence. ETHICS AND DISSEMINATION: The FORECAST study has received ethical approval (South Central Oxford C, 18/SC/0263). The dissemination strategy will be guided by our patient and public engagement activities and will include peer-reviewed publications, conference presentations, social media and podcasts. TRIAL REGISTRATION NUMBER: ISRCTN18170726; Pre-results.

Association between the number of chronic pain sites and neuropathic-like symptoms in community-dwelling older adults with chronic pain: a cross-sectional study.

OBJECTIVES: We investigated the relationship between the number of chronic pain sites and the prevalence and severity of neuropathic-like symptoms in community-dwelling older Japanese adults with chronic pain. DESIGN: Cross-sectional study. SETTING: The data analysed are from a study conducted in the city of Itoshima, Japan in 2017. PARTICIPANTS: The study population was 988 participants (age 65-75 years) not in need of long-term care who completed questionnaires assessing sociodemographic factors, psychological factors and chronic pain. PRIMARY OUTCOME MEASURES: The primary outcome was the participants' neuropathic-like symptoms evaluated by the PainDETECT Questionnaire (PD-Q). We classified the participants into mild and moderate-to-severe pain groups according to the pain intensity on the PD-Q. The number of chronic pain sites was categorised into groups with 1, 2-3 and ≥4 sites. RESULTS: The age-adjusted and sex-adjusted prevalence of neuropathic-like symptoms was significantly higher among the participants with 2-3 or ≥4 sites compared with the single-site group. In the binomial logistic regression analyses, the multivariable-adjusted ORs and 95% CIs for neuropathic-like symptoms among the participants with 2-3 and ≥4 sites were 1.94 (1.13 to 3.33) and 3.90 (2.22 to 6.85), respectively compared with the participants with single-site pain. The ORs for moderate-to-severe neuropathic-like symptoms increased significantly with the increase in the number of chronic pain sites. CONCLUSIONS: The number of chronic pain sites was positively associated with the presence and severity of neuropathic-like symptoms in community-dwelling older Japanese adults with chronic pain.

Mindful SensoriMotor Therapy combined with brain modulation for the treatment of pain in individuals with disarticulation or nerve injuries: a single-arm clinical trial.

INTRODUCTION: Neuropathic pain is a complex and demanding medical condition that is often difficult to treat. Regardless of the cause, the impairment, lesion or damage to the nervous system can lead to neuropathic pain, such as phantom limb pain (PLP). No treatment has been found widely effective for PLP, but plasticity-guided therapies have shown the least severe side effects in comparison to pharmacological or surgical interventions. Phantom motor execution (PME) is a plasticity-guided intervention that has shown promising results in alleviating PLP. The potential mechanism underlying the effectiveness of PME can be explained by the Stochastic Entanglement hypothesis for neurogenesis of neuropathic pain resulting from sensorimotor impairment. We have built on this hypothesis to investigate the efficacy of enhancing PME interventions by using phantom motor imagery to facilitate execution and with the addition of sensory training. We refer to this new treatment concept as Mindful SensoriMotor Therapy (MiSMT). In this study, we further complement MiSMT with non-invasive brain modulation, specifically transcranial direct current stimulation (tDCS), for the treatment of neuropathic pain in patients with disarticulation or peripheral nerve injury. METHODS AND ANALYSIS: This single-arm clinical trial investigates the efficacy of MiSMT and tDCS as a treatment of neuropathic pain resulting from highly impaired extremity or peripheral nerve injury in eight participants. The study consists of 12 sessions of MiSMT with anodal tDCS in the motor cortex, pretreatment and post-treatment assessments, and follow-up sessions (up to 6 months). The primary outcome is the change in pain intensity as measured by the Pain Rating Index between the first and last treatment sessions. ETHICS AND DISSEMINATION: The study is performed under the approval of the governing ethical committee in Sweden (approval number 2020-07157) and in accordance with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT04897425.

Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study.

INTRODUCTION: Whiplash-associated disorder grade 2 (WAD2) is characterised by musculoskeletal pain/tenderness but no apparent nerve injury. However, studies have found clinical features indicative of neuropathy and neuropathic pain. These studies may indicate peripheral nerve inflammation, since preclinical neuritis models found mechanical sensitivity in inflamed, intact nociceptors. The primary aim of this study is to establish the contribution of peripheral neuroinflammation to WAD2 and its role in prognosis. Participants will be invited to participate in a sub-study investigating the contribution of cutaneous small fibre pathology to WAD2. METHODS AND ANALYSIS: 115 participants within 1 month following whiplash injury and 34 healthy control participants will be recruited and complete validated questionnaires for pain, function and psychological factors. Data collection will take place at the Universities of Sussex and Oxford, UK. Clinical examination, quantitative sensory testing and blood samples will be undertaken. MRI scans using T2-weighted and diffusion tensor images of the brachial plexus and wrist will determine nerve inflammation and nerve structural changes. Skin biopsies from a substudy will determine structural integrity of dermal and intraepidermal nerve fibres. At 6 months, we will evaluate recovery using Neck Disability Index and a self-rated global recovery question and repeat the outcome measures. Regression analysis will identify differences in MRI parameters, clinical tests and skin biopsies between participants with WAD2 and age/gender-matched controls. Linear and logistic regression analyses will assess if nerve inflammation (MRI parameters) predicts poor outcome. Mixed effects modelling will compare MRI and clinical measures between recovered and non-recovered participants over time. ETHICS AND DISSEMINATION: Ethical approval was received from London-Brighton and Sussex Research Ethics Committee (20/PR/0625) and South Central-Oxford C Ethics Committee (18/SC/0263). Written informed consent will be obtained from participants prior to participation in the study. Results will be disseminated through publications in peer-reviewed journals, presentations at national/international conferences and social media. TRIAL REGISTRATION NUMBER: NCT04940923.

Symptom descriptors and patterns in lumbar radicular pain caused by disc herniation: a 1-year longitudinal cohort study.

OBJECTIVE: The objective of the present study was to explore the diversity, quality, severity and distribution of symptoms in patients with radicular pain and a lumbar disc herniation. DESIGN: Longitudinal cohort study. SETTING: Hospital-based back clinic. PARTICIPANTS: Ninety patients referred to secondary healthcare with (a) low back-related leg pain, (b) age between 18 and 65 years and (c) MRI confirmed lumbar disc herniation at a relevant side and level. OUTCOME MEASURES: Neuropathic pain symptoms were assessed using the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) and the painDETECT Questionnaire. In a subsample classified with neuropathic pain, in-depth interviews were performed, and symptomatic areas were drawn on standardised body charts. RESULTS: At baseline, the most frequently used painDETECT symptom descriptor was numbness sensation, reported by 94%, followed by sudden pain attacks and tingling or prickling. The mean (SD) SF-MPQ-2 score (0-10) for aching pain was 5.9 (2.8); numbness 4.3 (3.3); tingling 4.0 (3.4); burning 2.6 (3.1); pain caused by light touch 1.5 (2.6). Leg pain was rated as extremely bothersome by 73%, numbness and tingling by 38%, weakness by 24% and back pain by 17%. In the subsample (n=52), deep-lying pain and non-painful abnormal sensations were frequent, at 71% and 85%. Drawings demonstrated substantial overlap between symptoms from compromised L5 and the S1 nerve roots. Painful and non-painful symptoms improved at approximately the same rate. At the 1-year follow-up, 45% (14/31) of patients who had received disc surgery, and 34% (18/53) of those who had received conservative treatment reported no bothersome back pain, leg pain, numbness/tingling or weakness. CONCLUSION: Patients reported several highly bothersome symptoms, but not all are described as painful. The overall symptom profile of lumbar disc-related radicular pain differs from other neuropathic pain conditions with limited allodynia and thermal hyperalgesia. Symptomatic areas for the L5 and S1 nerve roots have a large overlap.

Swedish Chronic Pain Biobank: protocol for a multicentre registry and biomarker project.

INTRODUCTION: About 20% of the adult population have chronic pain, often associated with psychological distress, sick leave and poor health. There are large variations in the clinical picture. A biopsychosocial approach is used in investigation and treatment. The concept of personalised medicine, that is, optimising medication types and dosages for individual patients based on biomarkers and other patient-related factors, has received increasing attention in different diseases but used less in chronic pain. This cooperative project from all Swedish University Hospitals will investigate whether there are changes in inflammation and metabolism patterns in saliva and blood in chronic pain patients and whether the changes correlate with clinical characteristics and rehabilitation outcomes. METHODS AND ANALYSIS: Patients at multidisciplinary pain centres at University Hospitals in Sweden who have chosen to participate in the Swedish Quality Registry for Pain Rehabilitation and healthy sex-matched and age-matched individuals will be included in the study. Saliva and blood samples will be collected in addition to questionnaire data obtained from the register. From the samples, proteins, lipids, metabolites and micro-RNA will be analysed in relation to, for example, diagnosis, pain characteristics, psychological distress, body weight, pharmacological treatment and clinical rehabilitation results using advanced multivariate data analysis and bioinformatics. ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority (Dnr 2021-04929) and will be conducted in accordance with the declaration of Helsinki.The results will be published in open access scientific journals and in popular scientific relevant journals such as those from patient organisations. Data will be also presented in scientific meetings, meeting with healthcare organisations and disseminated in different lecturers at the clinics and universities.

Efficacy of indwelling trocar therapy for postherpetic neuralgia: A retrospective study of an acupuncture method.

Postherpetic neuralgia (PHN) is a common complication of herpes zoster. As a kind of continuous acupuncture, indwelling trocar therapy (ITT) involves inserting a trocar into the skin and retaining the soft cannula in the body for 24 h. However, the efficacy and safety of ITT on PHN require further verification. In this study, the medical records of 122 patients with PHN were retrospectively analyzed. Patients were divided into the control group (patients who received conventional drug therapy) and the ITT group (patients who underwent ITT combined with conventional drug therapy). The Visual Analog Scale (VAS), Quality of Sleep (QS), 36-Item Short Form Health Survey (SF-36), dosage of drug and adverse events were analyzed at days 1, 3, 7, 14, 28, 90, and 180 after treatment. The total efficiency rate (TER) was analyzed after 6 months of follow-up. The VAS, QS and SF-36 scores in the ITT group improved substantially compared with those in the control group after 6 months of follow-up (p < 0.001). The average dosage of anticonvulsants and analgesics decreased significantly in the ITT group (p < 0.001). The TER in the control group was 52.46%, compared with 73.77% in the ITT group (p < 0.05). There were no adverse events, such as bleeding and infection, observed in the ITT group. For PHN patients, the combination of ITT and medicine therapy reduced VAS, improved quality of life, increased the efficiency rate, remarkably reduced the dosage of traditional medicine, and had no significant side effects. In addition, ITT was more effective in patients with a short duration of PHN than in chronic PHN patients.

Low level light therapy/photobiomodulation for diabetic peripheral neuropathy: protocol of a systematic review and meta-analysis.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that strongly impact the patients' quality of life and working ability. Evidence indicated that low level light therapy (LLLT)/photobiomodulation might be effective for neuropathy. However, the effect of LLLT for DPN is not clear. The objective of this systematic review and meta-analysis is to determine the effects and safety of LLLT/photobiomodulation for DPN, in comparison with other methods such as sham light, no treatment, other active treatment and LLLT as an additional treatment compared with another treatment alone. METHODS AND ANALYSIS: We will search eight databases from their inception to the date before the review submission. Randomised controlled trials (RCTs) will be included. Two reviewers will independently extract data using a structured data extraction method and assess the risk of bias in the included studies. Data will be synthesised using standardised mean difference or risk ratio with 95% CIs for continuous and dichotomous data, respectively. The primary outcome will be change in pain and secondary outcomes will include global symptom improvement, functional impairment and disability, impairment of sensation, quality of life, nerve conduction, and adverse events. Sensitivity and subgroup analysis will be employed to explore the influence of possible clinical and methodological characteristics. Publication bias will be assessed using funnel plot. We will conduct meta-analysis with RevMan V.5.4 and evaluate quality of the evidence using GRADE approach. ETHICS AND DISSEMINATION: This study does not require ethics approval. Our findings will be disseminated in the peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021276056.