Accepted

Irritable bowel syndrome (IBS) is a common multifactorial condition that affects the large intestine and is characterized by chronic and relapsing abdominal pain and altered bowel habit. IBS is due to a combination of genetic, environmental and dietary factors. It's usually a lifelong problem very frustrating to live with and can have a big impact on quality of life, as single-agent therapy ra.

Chronic low back pain (CLBP) is among the leading causes of disability worldwide. Beyond the physical and functional limitations, people's beliefs, cognitions, and perceptions of their pain can negatively influence their prognosis. Altered cognitive and affective behaviors, such as pain catastrophizing and kinesiophobia, are correlated with changes in the brain and share a dynamic and bidirectional relationship. Similarly, in the presence of persistent pain, attentional control mechanisms, which serve to organize relevant task information are impaired. These deficits demonstrate that pain may be a predominant focus of attentional resources, leaving limited reserve for other cognitively demanding tasks. Cognitive dysfunction may limit one's capacity to evaluate, interpret, and revise the maladaptive thoughts and behaviors associated with catastrophizing and fear. As such, interventions targeting the brain and resultant behaviors are compelling. Pain neuroscience education (PNE), a cognitive intervention used to reconceptualize a person's pain experiences, has been shown to reduce the effects of pain catastrophizing and kinesiophobia. However, cognitive deficits associated with chronic pain may impact the efficacy of such interventions. Non-invasive brain stimulation (NIBS), such as transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective in the treatment of anxiety, depression, and pain. In addition, as with the treatment of most physical and psychological diagnoses, an active multimodal approach is considered to be optimal. Therefore, combining the neuromodulatory effects of NIBS with a cognitive intervention such as PNE could be promising. This review highlights the cognitive-affective deficits associated with CLBP while focusing on current evidence for cognition-based therapies and NIBS.

Chronic pain (CP) is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage lasting longer than 3 months. CP is the main reason why people seek medical care and exerts an enormous economic burden. Genome-wide expression analysis has revealed that diverse essential genetic elements are altered in CP patients. Although many possible mechanisms of CP have been revealed, we are still unable to meet all the analgesic needs of patients. In recent years, non-coding RNAs (ncRNAs) have been shown to play essential roles in peripheral neuropathy and axon regeneration, which is associated with CP occurrence and development. Multiple key ncRNAs have been identified in animal models of CP, such as microRNA-30c-5p, ciRS-7, and lncRNA MRAK009713. This review highlights different kinds of ncRNAs in the regulation of CP, which provides a more comprehensive understanding of the pathogenesis of the disease. It mainly focuses on the contributions of miRNAs, circRNAs, and lncRNAs to CP, specifically peripheral neuropathic pain (NP), diabetic NP, central NP associated with spinal cord injury, complex regional pain syndrome, inflammatory pain, and cancer-induced pain. In addition, we summarize some potential ncRNAs as novel biomarkers for CP and its complications. With an in-depth understanding of the mechanism of CP, ncRNAs may provide novel insight into CP and could become new therapeutic targets in the future.

Chronic pain can be difficult to predict and a challenge to treat. Biomarkers for chronic pain signal an opportunity for advancements in both management and prevention, and through their research and development offer new insights into the complex processes at play. This review considers the latest research in chronic pain biomarker development and considers how close we are to bringing these from bench to bedside. While some headway has been made that offers efficiencies in patient selection, it is unlikely that a single test will encompass the variety of chronic pain phenotypes. We offer some insights for the near future in biomarker development and areas of continued unmet need.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are structurally related neuropeptides that are widely expressed in vertebrate tissues. The two neuropeptides are pleiotropic and have been associated with migraine pathology. Three PACAP and VIP receptors have been described: PAC1, VPAC1, and VPAC2. The localization of these receptors in relation to VIP and PACAP in migraine-relevant structures has not previously been shown in mice. In the present study, we used fluorescence immunohistochemistry, well-characterized antibodies, confocal microscopy, and three-dimensional reconstruction to visualize the distribution of PACAP, VIP, and their receptors in the basal blood vessels (circle of Willis), trigeminal ganglion, and brain stem spinal trigeminal nucleus (SP5) of the mouse CNS. We demonstrated a dense network of circularly oriented VIP fibers on the basal blood vessels. PACAP nerve fibers were fewer in numbers compared to VIP fibers and ran along the long axis of the blood vessels, colocalized with calcitonin gene-related peptide (CGRP). The nerve fibers expressing CGRP are believed to be sensorial, with neuronal somas localized in the trigeminal ganglion and PACAP was found in a subpopulation of these CGRP-neurons. Immunostaining of the receptors revealed that only the VPAC1 receptor was present in the basal blood vessels, localized on the surface cell membrane of vascular smooth muscle cells and innervated by VIP fibers. No staining was seen for the PAC1, VPAC1, or VPAC2 receptor in the trigeminal ganglion. However, distinct PAC1 immunoreactivity was found in neurons innervated by PACAP nerve terminals located in the spinal trigeminal nucleus. These findings indicate that the effect of VIP is mediated via the VPAC1 receptor in the basal arteries. The role of PACAP in cerebral arteries is less clear. The localization of PACAP in a subpopulation of CGRP-expressing neurons in the trigeminal ganglion points toward a primary sensory function although a dendritic release cannot be excluded which could stimulate the VPAC1 receptor or the PAC1 and VPAC2 receptors on immune cells in the meninges, initiating neurogenic inflammation relevant for migraine pathology.

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA.

To estimate the prevalence of chronic back pain (CBP) and its associated factors.

Endometriosis (EMS) is a chronic disease that can cause dysmenorrhea, chronic pelvic pain, and infertility, among other symptoms. EMS diagnosis is often delayed compared to other chronic diseases, and there are currently no accurate, easily accessible, and non-invasive diagnostic tools. Therefore, it is important to elucidate the mechanism of EMS and explore potential biomarkers and diagnostic tools for its accurate diagnosis and treatment. In the present study, we comprehensively analyzed the differential expression, immune infiltration, and interactions of EMS-related genes in three datasets. Our results identified 332 differentially expressed genes (DEGs) associated with EMS. Gene ontology analysis showed that these changes mainly focused on the positive regulation of endometrial cell proliferation, cell metabolism, and extracellular space, and EMS involved the integrin, complement activation, folic acid metabolism, interleukin, and lipid signaling pathways. The LASSO regression model was established using immune DEGs with an area under the curve of 0.783 for the internal dataset and 0.656 for the external dataset. Five genes with diagnostic value, , , , , and , were screened from M1 and M2 macrophages, activated mast cells, neutrophils, natural killer cells, follicular T helper cells, CD8, and CD4 cells. A protein-protein interaction network based on the immune DEGs was constructed, and ten hub genes with the highest scores were identified. Our results may provide a framework for the development of pathological molecular networks in EMS.