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The discovery of calcitonin gene-related peptide (CGRP) and its role in migraine has promoted a new era in migraine treatment: CGRP antagonism. Two classes of medications are currently available: small molecules targeting the CGRP receptor and monoclonal antibodies targeting the CGRP receptor or CGRP ligand. The revolution of these medications is represented by blurring the borders between acute and preventive treatments, episodic and chronic migraine, naïve and refractory patients and even between migraine and other headache disorders.
Learn More >To assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia.
Learn More >Argentina has one of the largest territories in the world, which spreads over a lengthy latitudinal span. Its population is mainly composed of a mixture of South American natives and the descendants of numerous waves of European immigrants. Results from a previous study suggested that the prevalence of migraine in Argentina is the lowest in the region. Here we aimed to reassess the prevalence of migraine in Argentina applying a more sensitive and specific screening tool.
Learn More >The proper detection and behavioral response to painfully cold temperatures is critical for avoiding potentially harmful tissue damage. Cold allodynia and hyperalgesia, pain associated with innocuous cooling and exaggerated pain with noxious cold, respectively, are common in patients with chronic pain. In peripheral somatosensory afferents, the ion channels transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) are candidate receptors for innocuous and noxious cold temperatures, respectively. However, the role of TRPA1 as a cold sensor has remained controversial, and recent evidence suggests that TRPM8 channels and afferents mediate the detection of both pleasant and painful cold. To determine the role of TRPA1 afferents in cold-induced mouse behaviors in vivo, we used functional phenotyping by targeted nerve conduction block with the cell-impermeant lidocaine derivative QX-314. Surprisingly, we find that injection of QX-314 with TRPA1 agonists reduces cold-induced behaviors in mice, but does so in a TRPM8-dependent manner. Moreover, this effect is sexually dimorphic and requires the glial cell line-derived neurotrophic factor receptor GFRα3, as does cold hypersensitivity produced by the activation of TRPA1 channels. Taken together, these results suggest that under conditions of neurogenic inflammation, TRPA1 works upstream of GFRα3 and TRPM8 to produce cold hypersensitivity, providing novel insights into the role of TRPA1 channels in cold pain.
Learn More >TWIK-related spinal cord potassium channel (TRESK) background potassium channels have a key role in controlling resting membrane potential and excitability of sensory neurons. A frameshift mutation leading to complete loss of TRESK function has been identified in members of a family suffering from migraine with aura. In the present study, we examined the role of TRESK channels on nociceptor function in mice.
Learn More >There is significant heterogeneity in pain outcomes following motor vehicle crashes (MVCs), such that a sizeable portion of individuals develop symptoms of chronic pain months after injury while others recover. Despite variable outcomes, the pathogenesis of chronic pain is currently unclear. Previous neuroimaging work implicates the dorsal anterior cingulate cortex (dACC) in adaptive control of pain, while prior resting state functional magnetic resonance imaging studies find increased functional connectivity (FC) between the dACC and regions involved in pain processing in those with chronic pain. Hyper-connectivity of the dACC to regions that mediate pain response may therefore relate to pain severity. The present study completed rsfMRI scans on N = 22 survivors of MVCs collected within 2 weeks of the incident to test whole-brain dACC-FC as a predictor of pain severity 6 months later. At 2 weeks, pain symptoms were predicted by positive connectivity between the dACC and the premotor cortex. Controlling for pain symptoms at 2 weeks, pain symptoms at 6 months were predicted by negative connectivity between the dACC and the precuneus. Previous research implicates the precuneus in the individual subjective awareness of pain. Given a relatively small sample size, approximately half of which did not experience chronic pain at 6 months, findings warrant replication. Nevertheless, this study provides preliminary evidence of enhanced dACC connectivity with motor regions and decreased connectivity with pain processing regions as immediate and prospective predictors of pain following MVC. PERSPECTIVE: This article presents evidence of distinct neural vulnerabilities that predict chronic pain in MVC survivors based on whole-brain connectivity with the dorsal anterior cingulate cortex.
Learn More >The nociceptive flexion reflex (NFR) is used in neurophysiological research as an objective measure of nociception. NFR thresholds are reduced in numerous chronic pain pathologies, which are indicative of common central hyperexcitability within conditions. However, variation exists in both the NFR assessment and determinants of NFR threshold among research groups. Our purpose was to provide a review of the recent literature to (a) confirm the NFR threshold's efficacy in identifying those with chronic pain compared to controls and (b) provide a narrative synthesis on the current methodology used to assess the NFR in clinical populations. We conducted a review of multiple databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and Cochrane Library), including articles that reported controlled clinical studies of humans, in English, comparing NFR thresholds within chronic pain conditions to matched control subjects, published since the last NFR review in 2010. Our search resulted in nine studies included in our narrative synthesis and eight studies included in a meta-analysis. There was a significant pooled standardized mean difference in NFR threshold between chronic pain conditions and controls (-0.94, 95% confidence interval (CI) -1.33 to -0.55, < 0.0001), with substantial heterogeneity of pooled estimates ( = 87%, = 0.41, = 76.13, the degrees of freedom (df) = 11, < 0.0001). Significant variations in participant positioning, stimulation parameters and determinants of the NFR threshold were evident among included studies. We provided a narrative synthesis on the methodologies of included studies, as a recommendation for future studies in the assessment of the NFR in chronic pain.
Learn More >To estimate the prevalence, burden and current treatment of disabling primary headaches in a large sample of the Greek population aged 18-70 years old.
Learn More >Pain is a universal phenomenon, but is also inherently private and subjective – there's no objective test for its existence. Sufferers rely on language to describe their pain experience. The McGill Pain Questionnaire paved the way for incorporating language into pain assessment and recent research has explored aspects of pain language such as metaphors and grammatical patterns. This study investigated how chronic pain sufferers use language to describe their pain experience. Three focus groups were conducted ( = 16, age 22-74 years, = 46.6 years) with participants attending an outpatient chronic pain management program in Sydney, Australia. Participants were asked to describe aspects of their pain experience. The language which participants utilized to talk about their pain experience. Thematic analysis identified five superordinate themes: Isolation, Physical Sensations of Pain, Pain Personified, Pain as Overwhelming, and Coping with Pain. Across themes, participants relied on metaphorical language, which reflects the complex, multidimensional aspects of pain as well as the desire to effectively communicate it to others. This study underscores research indicating the complexity of pain experience and hence pain language, and suggests that single word adjectival measures are inadequate to completely capture its complexity. IMPLICATIONS FOR REHABILITATION Chronic pain is now considered a disease in and of itself, with patient's pain language being an important study area due to the lack of objective tests for pain. In both assessment and rehabilitation, patients rely on metaphorical pain language in order to facilitate understanding and garner support from others. Pain metaphors may provide a useful target for interventions such as Acceptance and Commitment Therapy and Cognitive Behavioural Therapy, particularly when addressing catastrophic thinking patterns.
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