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Calcitonin gene-related peptide (CGRP) is involved in several of the pathophysiological processes underpinning migraine attacks. Therapies that target CGRP or its receptor have shown efficacy as preventive or acute treatments for migraine. Two small-molecule CGRP receptor antagonists (rimegepant and ubrogepant) are approved for the acute treatment of migraine, and four monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab) are approved for migraine prevention; erenumab targets the canonical CGRP receptor, the others CGRP ligand. CGRP plays a role in gastrointestinal nociception, inflammation, gastric acid secretion, and motility. Nausea and vomiting are among the gastrointestinal symptoms associated with migraine, but individuals with migraine may also experience functional upper and lower gastrointestinal comorbidities, such as gastroesophageal reflux disease, gastroparesis, functional diarrhea or constipation, and irritable bowel syndrome. Although gastrointestinal symptoms in migraine can be treatment-related, they may also be attributable to increased CGRP. In this review, we summarize the epidemiological evidence for associations between migraine and gastrointestinal disorders, consider the possible physiological role of CGRP in these associations, and review the clinical occurrence of gastrointestinal events in patients with migraine receiving CGRP-based therapies and other migraine treatments. Because patients with migraine are at an increased risk of comorbid and treatment-related gastrointestinal effects, we also propose a patient-management strategy to mitigate these effects.
Learn More >People with chronic pain often fear and avoid movements and activities that were never paired with pain. Safe movements may be avoided if they share some semantic relationship with an actual pain-associated movement. The current study investigated whether pain-associated operant responses (movements) can become categorically associated with perceptually dissimilar responses, thus motivating avoidance of new classes of safe movements – a phenomenon known as category-based avoidance generalization. Using a robotic arm, two groups were trained to categorize arm-movements in different ways. Subsequently, the groups learned through operant conditioning, that an arm-movement from one of the categories was paired with a high probability of pain, while the others were paired with either a medium probability, and no pain (acquisition phase). Self-reported pain-related fear and pain-expectancy were collected as indices of fear learning. During a final generalization test phase, the movements categorically related to those from the acquisition phase were made available but in the absence of pain. Results showed that the generalization of outcome measures depended on the categorical connections between arm-movements, that is, the groups avoided and feared the novel generalization movement categorically related to the pain-associated acquisition movement, depending on how they had previously learned to categorize the movements. This suggests that operant pain-related avoidance can generalize to safe behaviors, which are not perceptually, but categorically, similar to a pain-associated behavior. This form of pain-related avoidance generalization is problematic because category-based relations can be extremely wide reaching and idiosyncratic. Thus, category-based generalization of operant pain-related avoidance merits further investigation.
Learn More >Trigeminal neuralgia (TN) is a unique pain disorder characterized by intense paroxysmal facial pain within areas innervated by the trigeminal nerve. Although most cases of TN are sporadic, familial clusters of TN suggest that genetic factors may contribute to this disorder. Whole-exome sequencing in patients with TN reporting positive family history demonstrated a spectrum of variants of ion channels including TRP channels. Here, we used patch-clamp analysis and Ca and Na imaging to assess a rare variant in the TRPM7 channel, p.Ala931Thr, within transmembrane domain 3, identified in a man suffering from unilateral TN. We showed that A931T produced an abnormal inward current carried by Na and insensitive to the pore blocker Gd. Hypothesizing that replacement of the hydrophobic alanine at position 931 with the more polar threonine destabilizes a hydrophobic ring, near the voltage sensor domain, we performed alanine substitutions of F971 and W972 and obtained results suggesting a role of A931-W972 hydrophobic interaction in S3-S4 hydrophobic cleft stability. Finally, we transfected trigeminal ganglion neurons with A931T channels and observed that expression of this TRPM7 variant lowers current threshold and resting membrane potential, and increases evoked firing activity in TG neurons. Our results support the notion that the TRPM7-A931T mutation located in the S3 segment at the interface with the transmembrane region S4, generates an omega current that carries Na influx in physiological conditions. A931T produces hyperexcitability and a sustained Na influx in trigeminal ganglion neurons that may underlie pain in this kindred with trigeminal neuralgia.
Learn More >Chronic pain (CP) among adolescents has received less attention than adultsandthere is limited qualitative studies about it in Iran. This study explored the experience of CP among adolescents.
Learn More >Melanocytes are surrounded by diverse cells, including sensory neurons in our skin, but their interaction and functional importance have been poorly investigated. In this study, we find that melanocytes and nociceptive neurons contact more in human skin color patch tissue than control. Co-culture with human iPSC-derived sensory neurons significantly induces morphogenesis and pigmentation of human melanocytes. To reveal melanocyte-stimulating factors secreted from neurons, we perform proteomic analyses and identify RGMB in the sensory neuron-conditioned medium. RGMB protein induces morphogenesis and melanin production of melanocytes, demonstrating that RGMB is a melanocyte-stimulating factor released from sensory neurons. Transcriptome analysis suggests that the melanosome transport machinery can be controlled by RGMB, leading us to identify the vesicle production response of melanocytes upon RGMB treatment. This study discovers a role of sensory neurons in modulating multiple aspects of human melanocytes through secretion of a key factor: RGMB.
Learn More >Endometriosis is a chronic pain condition affecting 1 in 10 women. There is an unmet need for better medical treatments for endometriosis. We spotlight trials of a single preparation combined HRT-GnRH antagonist (Relugolix) by Giudice et al., for endometriosis-associated pain.
Learn More >The main aim was to determine the effects of percutaneous (PENS) and transcutaneous (TENS) electrical nerve stimulation on endogenous pain mechanisms in patients with musculoskeletal pain.
Learn More >The number of regular smartphone users has increased dramatically worldwide. Headaches, followed by sleep difficulties, forgetfulness, dizziness, and other ailments, are among the most prevalent complaints among smartphone users during or after use. In addition, migraine is a debilitating disease and is the world's second leading cause of disability. Hence, we performed this study to determine how smartphone overuse influenced migraine patients' level of disability, pain intensity, sleep quality, and overall quality of life.
Learn More >Chronic pain is associated with high levels of psychological distress, which can have implications for general functioning, acceptance, quality of life, and compliance with health-promoting behaviour. This study explored the association between pain-related factors and psychological distress in a sample of patients with long lasting temporomandibular disorder (TMD). In this cross-sectional study design, psychological distress was measured in 133 Norwegian patients with long lasting and severe TMD. Participants completed a survey including the hospital anxiety and depression scale (HADS), and questions about pain intensity, pain duration, catastrophizing, and causal attributions of their TMD symptoms along with a clinical interdisciplinary investigation. Higher levels of catastrophizing were associated with psychological distress. Pain intensity was associated with psychological distress in the unadjusted model, but not when controlling for the other variables. The majority attributed their TMD symptoms to physical factors. The findings support psychological interventions aimed at reducing catastrophizing in treatment of TMD. However, the patients emphasized physical causes for their TMD symptoms, suggesting that psychological interventions alone are not sufficient. The findings support a multidisciplinary approach to the treatment of TMD.
Learn More >Epidural analgesia alleviates pain during normal labour but women who undergo medical abortion procedures using epidural analgesia continue to express high pain levels. To understand this we assessed if patients undergoing medical abortions, treated with epidural analgesia, use their pain for psychological benefits.
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