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Neuropathic pain is an unfavorable pathological pain, often persistent over time, thus leading to significant impairment of quality of life and public health burden. Notably, microRNAs (miRNAs) have been implicated in the pathophysiological process of neuropathic pain. The potential mechanism by which miR-34c-5p functions in neuropathic pain remains unclear. This study aimed to test the hypothesis that miR-34c-5p can modulate neuropathic pain in rat models with chronic constriction injury (CCI) of sciatic nerve, via interaction with the SIRT1/STAT3 signaling pathway Firstly, SIRT1 was validated as a target gene of miR-34c-5p and could be negatively regulated by miR-34c-5p. We induced miR-34c-5p overexpression/inhibition, SIRT1 knockdown, and STAT3 knockdown in the model rats to assess pain behavior patterns. Meanwhile, dorsal root ganglion (DRG) was transduced with overexpression or knockdown of miR-34c-5p or lipopolysaccharide to induce the production of inflammatory factors. It was observed that miR-34c-5p was up-regulated, and SIRT1 was under-expressed in the DRG neurons of dorsal spinal cords of the CCI rats. Furthermore, the ectopic expression of miR-34c-5p and knockdown of SIRT1 in CCI rats resulted in increased hyperalgesia and inflammation, corresponding to reduced paw withdrawal threshold and paw withdrawal latency, and elevated levels of IL-6, IL-1β and TNF-α. More importantly, miR-34c-5p inhibition reduced the hyperalgesia and inflammation by blocking the STAT3 signaling pathway through up-regulation of SIRT1. Conjointly, our results indicated that the down-regulation of miR-34c-5p could potentially provide sustained relief in neuropathic pain by promoting SIRT1 expression through STAT3 signaling pathway inactivation.
Learn More >Clinically, chronic postsurgical pain (CPSP) is very common. Many CPSP patients may experience depression. Thus far, little is known about the mechanism of the comorbidity of CPSP and depression. Ketamine has been confirmed to possess analgesic and rapid antidepressant effects, but it is unclear whether ketamine can relieve the comorbidity of CPSP and depression.
Learn More >To assess the supraspinal working mechanisms of the Burst spinal cord stimulation (SCS)-mode we used functional magnetic resonance imaging (fMRI) in chronic neuropathic rats. We hypothesized that active recharge Burst SCS would induce a more profound BOLD signal increase in areas associated with cognitive-emotional aspects of pain, as compared to Tonic SCS.
Learn More >Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity.
Learn More >In response to the national opioid public health crisis, there is an urgent need to develop nonopioid solutions for effective pain management. Neurosteroids are endogenous molecules with pleotropic actions that show promise for safe and effective treatment of chronic low back pain.
Learn More >A comprehensive overview and safety evaluation of fremanezumab as a preventive therapy for migraine.
: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP mAb), is a migraine-specific treatment for migraine prevention.: This review will briefly discuss other available and emerging CGRP mAbs and the neurophysiology of fremanezumab. The review will focus on phase III trials of the efficacy of fremanezumab for episodic and chronic trials, and a recent pooled safety and tolerability analysis of its use.: Continued efficacy and safety data collection will help guide long-term risk and efficacy counseling in the general population.
Learn More >The physical therapy profession has recently begun to address its role in preventing and managing opioid use disorder (OUD). This topic calls for discussion of the scope of physical therapy practice, and the profession's role, in the prevention and treatment of complex chronic illnesses, such as OUD. OUD is not just an individual-level problem. Abundant scientific literature indicates OUD is a problem that warrants interventions at the societal level. This upstream orientation is supported in the American Physical Therapy Association's vision statement compelling societal transformation and its mission of building communities. Applying a population health framework to these efforts may provide physical therapists with a useful viewpoint that can inform clinical practice and research, as well as develop new cross-disciplinary partnerships. This Perspective discusses the intersection of OUD and persistent pain using the disease prevention model. Primordial, primary, secondary, and tertiary preventive strategies are defined and discussed. This Perspective then explains the potential contributions of this model to current practices in physical therapy, as well as provide actionable suggestions for physical therapists to help develop and implement upstream interventions that may reduce the impact of OUD in their communities.
Learn More >The objectives of this study were to obtain patient evaluations of the content, structure, and delivery modality of Meaning-Centered Pain Coping Skills Training (MCPC), a novel psychosocial intervention for patients with advanced cancer and pain. MCPC aims to help patients connect with valued sources of meaning in their lives (e.g., family relationships), while providing training in evidence-based cognitive and behavioral skills (e.g., guided imagery) to reduce pain.
Learn More >In recent decades, a growing number of structural neuroimaging studies of grey matter (GM) in trigeminal neuralgia (TN) have reported inconsistent alterations. We carried out a systematic review and meta-analysis to identify consistent and replicable GM volume abnormalities using effect-size signed differential mapping (ES-SDM). Furthermore, we conducted a meta-regression to explore the potential effects of clinical characteristics on GM volume alterations in patients with TN. A total of 13 studies with 15 datasets, representing 407 TN patients and 376 healthy individuals, were included in the present study. The results revealed that TN patients had GM volume abnormalities mainly in the basal ganglia, including the putamen, nucleus accumbens (NAc), caudate nucleus and amygdala, as well as the cingulate cortex (CC), thalamus, insula and superior temporal gyrus (STG). The meta-regression analysis showed that verbal rating scale (VRS) scores were negatively correlated with decreased GM volume in the left striatum and that illness duration was negatively correlated with decreased GM volume in the left STG and left insula. These results provide a thorough profile of GM volume alterations in TN patients and constitute robust evidence that aberrant GM volumes in the brain regions regulating and moderating sensory-motor and affective processing may play an important role in the pathophysiology of TN.
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