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The calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of several pain-related syndromes, including migraine. Targeting CGRP and its receptor by their antagonists and antibodies was a breakthrough in migraine therapy, but the need to improve efficacy and limit the side effects of these drugs justify further studies on the regulation of CGRP in migraine. The expression of the CGRP encoding gene, , is modulated by epigenetic modifications, including the DNA methylation, histone modification, and effects of micro RNAs (miRNAs), circular RNAs, and long-coding RNAs (lncRNAs). On the other hand, CGRP can change the epigenetic profile of neuronal and glial cells. The promoter of the gene has two CpG islands that may be specifically methylated in migraine patients. DNA methylation and lncRNAs were shown to play a role in the cell-specific alternative splicing of the primary transcript. CGRP may be involved in changes in neural cytoarchitecture that are controlled by histone deacetylase 6 (HDAC6) and can be related to migraine. Inhibition of HDAC6 results in reduced cortical-spreading depression and a blockade of the CGRP receptor. CGRP levels are associated with the expression of several miRNAs in plasma, making them useful peripheral markers of migraine. The fundamental role of CGRP in inflammatory pain transmission may be epigenetically regulated. In conclusion, epigenetic connections of CGRP should be further explored for efficient and safe antimigraine therapy.
Learn More >Fibromyalgia is a clinical condition that affects 1% to 5% of the population. No proper therapy has been currently found. It has been described that inflammation plays a central role in the nerve sensitizations that characterize the pathology.
Learn More >Food strategies are currently used to improve inflammation and oxidative stress conditions in chronic pain which contributes to a better quality of life for patients. The main purpose of this systematic review is to analyze the effectiveness of different dietary strategies as part of the treatment plan for patients suffering from chronic pain and decreased health. PubMed, Web of Science, ProQuest, Scopus, Cumulative Index to Nursing & Allied Health Literature (CINAHL), Cambridge Core, and Oxford Academy databases were used to review and to appraise the literature. Randomized clinical trials (RCT), observational studies, and systematic reviews published within the last 6 years were included. The Physiotherapy Evidence Database (PEDro) scale, the PEDro Internal Validity (PVI), the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a variety of fields (QUALSYT), and the Quality Assessment Tool of Systematic Reviews scale were used to evaluate the risk of bias of the included studies. A total of 16 articles were included, of which 11 were RCTs and 5 were observational studies. Six of them showed an improvement in pain assessment, while two studies showed the opposite. Inflammation was shown to be decreased in four studies, while one did not show a decrease. The quality of life was shown to have improved in five studies. All of the selected studies obtained good methodological quality in their assessment scales. In the PVI, one RCT showed good internal validity, five RCTs showed moderate internal quality, while five of them were limited. Current research shows that consensus on the effects of an IF diet on pain improvement, in either the short or the long term, is lacking. A caloric restriction diet may be a good long term treatment option for people suffering from pain. Time restricted food and ketogenic diets may improve the quality of life in chronic conditions. However, more studies analyzing the effects of different nutritional strategies, not only in isolation but in combination with other therapies in the short and the long term, are needed.
Learn More >Acute or chronic pain is a major source of impairment in quality of life and affects a substantial part of the population. To date, pain is alleviated by a limited range of treatments with significant toxicity, increased risk of misuse and inconsistent efficacy, owing, in part, to lack of specificity and/or unfavorable pharmacokinetic properties. Thanks to the unique properties of nanoscaled drug carriers, nanomedicine may enhance drug biodistribution and targeting, thus contributing to improved bioavailability and lower off-target toxicity. After a brief overview of the current situation and the main critical issues regarding pain alleviation, this review will examine the most advanced approaches using nanomedicine of each drug class, from the preclinical stage to approved nanomedicines.
Learn More >It is unclear whether the electrophysiological effects of erenumab, a monoclonal antibody against the calcitonin gene-related peptide receptor, occur only at the periphery of the trigeminal system or centrally and at the cortical level.
Learn More >Cancer-induced bone pain (CIBP) is a kind of pain with complex pathophysiology. Proteinase-activated receptor 2 (PAR-2) is involved in CIBP. This study explored the effects of PAR-2 on CIBP rats.
Learn More >Specific dietary recommendations for migraine patients with comorbid irritable bowel syndrome (IBS) are lacking. This work aimed to study the severity scores of such two common pain-related disorders in relation to various macronutrients and micronutrients intake.
Learn More >Chronic pain conditions, including temporomandibular disorders, are closely related to poor sleep quality. This study investigated whether sleep deterioration in patients with painful temporomandibular disorder differed depending on the origin of pain, and also analyzed which clinical disease characteristics and whether psychological distress affected sleep quality. A total of 337 consecutive patients (215 women; mean age, 33.01 ± 13.01 years) with painful temporomandibular disorder (myalgia [n=120], temporomandibular joint arthralgia [n=62], mixed joint-muscle temporomandibular disorder pain [n=155]), who were assessed and classified based on the diagnostic criteria for temporomandibular disorder (DC/TMD), were enrolled. They completed a battery of standardized reports on clinical sign and symptoms, and answered questions on sleep quality, excessive daytime sleepiness, and patients' psychological status. The mean global Pittsburgh Sleep Quality Index scores were significantly higher in the mixed temporomandibular disorder pain group (6.97 ± 3.38) and myalgia group (6.40 ± 3.22) than in the arthralgia group (5.16 ± 2.94) (p=0.001). Poor sleepers were significantly more prevalent in the mixed temporomandibular disorder pain group (76.8%) and myalgia group (71.7%) than in the arthralgia group (54.8%) (p=0.006). The presence of psychological distress in the myalgia group (β=1.236, p=0.022), global severity index of the Symptom Checklist-90-Revised in the arthralgia group (β=1.668, p=0.008), and presence of headache (β=1.631, p=0.002) and self-reported sleep problems (β=2.849, p<0.001) in the mixed temporomandibular disorder pain group were associated with an increase in the Pittsburgh Sleep Quality Index score. Ultimately, as the source of pain in painful temporomandibular disorder can affect and determine sleep quality and contributing factors, and as the complex interplay between sleep and pain can vary, a comprehensive treatment approach is necessary because good sleep is required by patients.
Learn More >Neuropathic pain affects millions of people worldwide, yet the molecular mechanisms of how it develops and persists are poorly understood. Given that males have historically been utilized as the primary sex in preclinical studies, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. Macrophages contribute to the development of neuroinflammatory pain via the activation of their cyclooxygenase-2 (COX-2) enzyme, which leads to the production of prostaglandin E (PGE). PGE activates nociception and influences additional leukocyte infiltration. Attenuation of COX-2 activity decreases inflammatory pain, most commonly achieved by nonsteroidal anti-inflammatory drugs (NSAIDs), yet NSAIDs are considered ineffective for neuropathic pain due to off target toxicity. Using chronic constriction injury of the rat sciatic nerve, we show that males and females exhibit quantitatively the same degree of mechanical allodynia post injury. Furthermore, a low-dose nanotherapeutic containing the NSAID celecoxib is phagocytosed by circulating monocytes that then naturally accumulate at sites of injury as macrophages. Using this nanotherapeutic, we show that treated males exhibit complete reversal of hypersensitivity, while the same dose of nanotherapeutic in females provides an attenuated relief. The difference in behavioral response to the nanotherapy is reflected in the reduction of infiltrating macrophages at the site of injury. The observations contained in this study reinforce the notion that female neuroinflammation is different than males.
Learn More >Quantitative data on longitudinal associations between catastrophizing and pain or physical function are patchy. The study aimed to quantify the prognostic value of catastrophizing for pain and function in fibromyalgia and low back pain before and after rehabilitation.
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