Accepted

Increasing evidence suggests that epigenetic mechanisms have great potential in the field of pain. The changes and roles of epigenetics of the spinal cord and dorsal root ganglia in the chronic pain process may provide broad insights for future pain management. Pro-inflammatory cytokines and chemokines released by microglia and astrocytes, as well as blood-derived macrophages, play critical roles in inducing and maintaining chronic pain, while histone modifications may play an important role in inflammatory metabolism. This review provides an overview of neuroinflammation and chronic pain, and we systematically discuss the regulation of neuroinflammation and histone modifications in the context of chronic pain. Specifically, we analyzed the role of epigenetics in alleviating or exacerbating chronic pain by modulating microglia, astrocytes, and the proinflammatory mediators they release. This review aimed to contribute to the discovery of new therapeutic targets for chronic pain.

Rheumatoid arthritis (RA) is a common systematic, chronic inflammatory, autoimmune, and polyarticular disease, causing a range of clinical manifestations, including joint swelling, redness, pain, stiffness, fatigue, decreased quality of life, progressive disability, cardiovascular problems, and other comorbidities. Strong evidence has shown that exercise is effective for RA treatment in various clinical domains. Exercise training for relatively longer periods (e.g., ≥ 12 weeks) can decrease disease activity of RA. However, the mechanism underlying the effectiveness of exercise in reducing RA disease activity remains unclear. This review first summarizes and highlights the effectiveness of exercise in RA treatment. Then, we integrate current evidence and propose biological mechanisms responsible for the potential effects of exercise on immune cells and immunity, inflammatory response, matrix metalloproteinases, oxidative stress, and epigenetic regulation. However, a large body of evidence was obtained from the non-RA populations. Future studies are needed to further examine the proposed biological mechanisms responsible for the effectiveness of exercise in decreasing disease activity in RA populations. Such knowledge will contribute to the basic science and strengthen the scientific basis of the prescription of exercise therapy for RA in the clinical routine.

Chronic low back pain (CLBP) is a musculoskeletal ailment that affects millions globally. The pain is disturbing associated with impaired motor activity, reduced flexibility, decreased productivity and strained interpersonal relationships leading to poor quality of life. Inflammatory mediators in vicinity of nociceptors and amplification of neural signals cause peripheral and central sensitization presented as hyperalgesia and/or allodynia. It could be attributed to either diminished descending pain inhibition or exaggerated ascending pain facilitation. Objective measurement of pain is crucial for diagnosis and management. Nociceptive flexion reflex is a reliable and objective tool for measurement of a subject's pain experience. Medical Yoga Therapy (MYT) has proven to relieve chronic pain, but objective evidence-based assessment of its effects is still lacking. We objectively assessed effect of MYT on pain and quality of life in CLBP patients. We recorded VAS (Visual analogue scale), McGill Pain questionnaire and WHOQOL BREF questionnaire scores, NFR response and Diffuse noxious inhibitory control tests. Medical yoga therapy consisted of an 8-week program (4 weeks supervised and 4 weeks at home practice). CLBP patients (42.5 ± 12.6 years) were randomly allocated to MYT ( = 58) and SCT groups ( = 50), and comparisons between the groups and within the groups were done at baseline and at end of 4 and 8 weeks of both interventions. (VAS) scores for patients in both the groups were comparable at baseline, subjective pain rating decreased significantly more after MYT compared to SCT (= < 0.0001*,  = 0.005*). McGill Pain questionnaire scores revealed significant reduction in pain experience in MYT group compared to SCT. Nociceptive Flexion Reflex threshold increased significantly in MYT group at end of 4 weeks and 8 weeks,  < 0.0001#, = < 0.0001∞ respectively) whereas for SCT we did not find any significant change in NFR thresholds. DNIC assessed by CPT also showed significant improvement in descending pain modulation after MYT compared to SCT both at end of 4 and 8 weeks. Quality of life also improved significantly more after MYT. Thus, we conclude with objective evidence that Medical Yoga Therapy relieves chronic low back pain, stress and improves quality of life better than standard care.

Chronic pain (CP) patients tend to represent aberrant functional brain activity. Acupuncture is an effective clinical treatment for CP, and some fMRI studies were conducted to discover the alternation of brain regions after acupuncture therapy for CP. However, the heterogeneity of neuroimaging studies has prevented researchers from systematically generalizing the central mechanisms of acupuncture in the treatment of CP.

Idiopathic scoliosis (IS) is a common spinal disorder. Although several studies have reported the benefits of manual therapy for patients with IS in improving pain, anxiety, depression, and spinal disorders, the efficacy of manual therapy in the management of IS remain controversial. Therefore, this review was conducted to assess effects of manual therapy in the management of IS, primarily on pain and mental health of the patients and secondarily on their spinal disorders.

Postherpetic neuralgia (PHN) is a clinical puzzle, especially in patients who still suffered from moderate and severe pain after standard treatment. This single-center, double-blinded, randomized controlled, prospective, and non-inferiority study observed the safety and effectiveness of the epidural application of morphine or hydromorphone, trying to provide an alternative method for those patients with refractory PHN. Eighty PHN patients with a visual analogue scale (VAS) still greater than 50 mm after routine management were randomly divided into two groups according to 1:1, respectively. One group received epidural morphine (EMO group), and the other group received epidural hydromorphone (EHM group). VAS, the number of breakthrough pain, quality of life (QOL), and anxiety/depression assessment (GAD-7 and PHQ-9 scores) were also observed before treatment, at 1, 3, 7, 14, 21, 28, 60, and 90 days after treatment, as well as side effects. Opioid withdrawal symptoms (OWSs) were also measured from 3 to 28 days after treatment. The EHM group was non-inferior to the EMO group in terms of the VAS decrease relative to baseline (VDRB) after 1-week treatment. The VAS of the two groups on all days after treatment was significantly lower than the corresponding baseline findings ( < 0.05). The breakthrough pain (BTP) decreased significantly after treatment and lasted until 14 days after treatment ( < 0.05). There was no significant difference in BTP between the two groups at each time point ( > 0.05). In terms of the QOL, GAD-7, and PHQ-9 outcomes, those were significantly improved after treatment ( < 0.05), and there was no difference between the two groups ( > 0.05). No significant AE difference across the two groups was observed in this study. Few reports of OWS were found in this trial, and there were no significant differences between the two groups ( > 0.05). EHM was non-inferior to EMO in terms of the VDRB after 1-week treatment. For patients with VAS still greater than 50 mm after standard treatment, short-term application of EMO or EHM can ameliorate intractable pain, improve the quality of life, and have no obvious side effects. Short-term epidural opioid application will not lead to the appearance of OWS.

Sciatica is a pain disorder often caused by the herniated disk compressing the lumbosacral nerve roots. Neuroimaging studies have identified functional abnormalities in patients with chronic sciatica (CS). However, few studies have investigated the neural marker of CS using brain structure and the classification value of multidimensional neuroimaging features in CS patients is unclear.