Accepted

A scoping review to synthesize evidence and assess articles describing the use of beta-endorphins as a pain biomarker in chronic pain patients treated with non-invasive brain stimulation techniques was systematically performed with respect to the study quality, the technique employed and the results. Independent reviewers determined if the article met the study criteria at each stage for it to be included. Content analysis was applied and summarized. The results are described in a narrative form grouped by pain condition, type of intervention, stimulation protocol, outcome measures and main results. A total of 67 of 73 references were excluded, and 6 identified studies met the inclusion criteria. The study design, sample size, stimulation type, session protocol and the main findings of each study were extracted. The studies in this scoping review ranged from unsatisfactory to good based on the adopted criteria, with no study achieving an excellent rating. There is limited evidence on the dosage of beta-endorphin in chronic pain conditions during treatment with NIBS. Based on this literature, evidence suggests that BE may not only be useful for acute and persistent pain, but also for a variety of chronic pain states in which opioids are not effective.

Knee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. Acupuncture has been proven to be an effective treatment for KOA. However, the neural mechanism of acupuncture is unclear, so far. Periaqueductal gray (PAG) and raphe nuclei (RPN) are essential structures associated with chronic pain in human brains. This study aims to investigate functional connectivity (FC) changes of PAG and RPN in KOA to interpret the neural mechanism of acupuncture.

The prevalence of chronic pain has reached epidemic levels. In addition to personal suffering chronic pain is associated with psychiatric and medical co-morbidities, notably substance misuse, and a huge a societal cost amounting to hundreds of billions of dollars annually in medical cost, lost wages, and productivity. Chronic pain does not have a cure or quantitative diagnostic or prognostic tools. In this manuscript we provide evidence that this situation is about to change. We first start by summarizing our current understanding of the role of the brain in the pathogenesis of chronic pain. We particularly focus on the concept of learning in the emergence of chronic pain, and the implication of the limbic brain circuitry and dopaminergic signaling, which underly emotional learning and decision making, in this process. Next, we summarize data from our labs and from other groups on the latest brain imaging findings in different chronic pain conditions focusing on results with significant potential for translation into clinical applications. The gaps in the study of chronic pain and brain imaging are highlighted in throughout the overview. Finally, we conclude by discussing the costs and benefits of using brain biomarkers of chronic pain and compare to other potential markers.

Pain management is an important priority in the treatment of acute pancreatitis (AP). Current evidence and guideline recommendations are inconsistent on the most effective analgesic protocol. This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to compare the safety and efficacy of analgesics for pain relief in AP. A literature search was performed to identify all RCTs assessing analgesics in patients with AP. The primary outcome was the number of participants who needed rescue analgesia. Study quality was assessed using Jadad score. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CI) were analysed using a random-effects model. Twelve studies comprising 699 patients with AP (83% mild AP) were analysed. The tested analgesics significantly decreased the need for rescue analgesia (3 studies, OR.36, 95% CI 0.21 to 0.60) vs. placebo or conventional treatment. The analgesics also improved the pain score [Visual Analogue Scale (Δ-VAS)] at 24 h (WMD 18.46, 0.84 to 36.07) and by the 3rd to 7th days (WMD 11.57, 0.87 to 22.28). Opioids vs. non-opioids were associated with a decrease in the need for rescue analgesia (6 studies, OR 0.25, 95% CI 0.07 to 0.86, = 0.03) but without significance in pain score. In subgroup analyses, opioids were similar to non-steroidal anti-inflammatory drugs (NSAIDs) regarding the primary outcome (4 studies, OR 0.56, 95% CI 0.24 to 1.32, = 0.18). There were no significant differences in other clinical outcomes and rate of adverse events. Other studies, comparing epidural anaesthesia vs. patient-controlled analgesia and opioid (buprenorphine) vs. opioid (pethidine) did not show significant difference in primary outcome. Study quality issues significantly contributed to overall study heterogeneity. NSAIDs and opioids are equally effective in decreasing the need for rescue analgesia in patients with mild AP. The relative paucity of trials and high-quality data in this setting is notable and the optimal analgesic strategy for patients with moderately severe and severe AP still requires to be determined.

Hereditary multiple exostoses (HMEs) syndrome, also known as multiple osteochondromas, represents a rare and severe human skeletal disorder. The disease is characterized by multiple benign cartilage-capped bony outgrowths, termed exostoses or osteochondromas, that locate most commonly in the juxta-epiphyseal portions of long bones. Affected individuals usually complain of persistent pain caused by the pressure on neighboring tissues, disturbance of blood circulation, or rarely by spinal cord compression. However, the most severe complication of this condition is malignant transformation into chondrosarcoma, occurring in up to 3.9% of HMEs patients. The disease results mainly from heterozygous loss-of-function alterations in the or genes, encoding Golgi-associated glycosyltransferases, responsible for heparan sulfate biosynthesis. Some of the patients with HMEs do not carry pathogenic variants in those genes, hence the presence of somatic mutations, deep intronic variants, or another genes/loci is suggested. This review presents the systematic analysis of current cellular and molecular concepts of HMEs along with clinical characteristics, clinical and molecular diagnostic methods, differential diagnosis, and potential treatment options.

Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases. The study aimed to summarize the effectiveness and efficacy of exercise for various diseases with NP supported by evidence, describe expert recommendations for NP from different causes, and inform policymakers of the guidelines. A systematic review and expert consensus. A systematic search was conducted in PubMed. We included systematic review and meta-analysis, randomized controlled trials (RCTs), which assessed patients with NP. Studies involved exercise intervention and outcome included pain intensity at least. Physiotherapy Evidence Database and the Assessment of Multiple Systematic reviews tool were used to grade the quality assessment of the included RCTs and systematic reviews, respectively. The final grades of recommendation were based on strength of evidence and a consensus discussion of results of Delphi rounds by the Delphi consensus panel including 21 experts from the Chinese Association of Rehabilitation Medicine. Eight systematic reviews and 21 RCTs fulfilled all of the inclusion criteria and were included, which were used to create the 10 evidence-based consensus statements. The 10 expert recommendations regarding exercise for NP symptoms were relevant to the following 10 different diseases: spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, cervical radiculopathy, sciatica, diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV/AIDS, and surgery, respectively. The exercise recommended in the expert consensus involved but was not limited to muscle stretching, strengthening/resistance exercise, aerobic exercise, motor control/stabilization training and mind-body exercise (Tai Chi and yoga). Based on the available evidence, exercise is helpful to alleviate NP intensity. Therefore, these expert consensuses recommend that proper exercise programs can be considered as an effective alternative treatment or complementary therapy for most patients with NP. The expert consensus provided medical staff and policymakers with applicable recommendations for the formulation of exercise prescription for NP. This consensus statement will require regular updates after five-ten years.