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Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain.

Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptive primary afferents, and underpins the mechanism for capsaicin-induced burning pain. Paradoxically, capsaicin has long been used as an analgesic. The development of topical patches and injectable formulations containing capsaicin has led to application in clinical settings to treat chronic pain conditions, such as neuropathic pain and the potential to treat osteoarthritis. More detailed determination of the neurobiological mechanisms of capsaicin-induced analgesia should provide the logical rationale for capsaicin therapy and help to overcome the treatment's limitations, which include individual differences in treatment outcome and procedural discomfort. Low concentrations of capsaicin induce short-term defunctionalization of nociceptor terminals. This phenomenon is reversible within hours and, hence, likely does not account for the clinical benefit. By contrast, high concentrations of capsaicin lead to long-term defunctionalization mediated by the ablation of TRPV1-expressing afferent terminals, resulting in long-lasting analgesia persisting for several months. Recent studies have shown that capsaicin-induced Ca/calpain-mediated ablation of axonal terminals is necessary to produce long-lasting analgesia in a mouse model of neuropathic pain. In combination with calpain, axonal mitochondrial dysfunction and microtubule disorganization may also contribute to the longer-term effects of capsaicin. The analgesic effects subside over time in association with the regeneration of the ablated afferent terminals. Further determination of the neurobiological mechanisms of capsaicin-induced analgesia should lead to more efficacious non-opioidergic analgesic options with fewer adverse side effects.

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Deficit in voluntary wheel running in chronic inflammatory and neuropathic pain models in mice: Impact of sex and genotype.

Patients with chronic pain report decreased general activity and emotional distress. Therefore, the development of various animal models that encompass different aspects of pain are crucial for the discovery of genetic differences and the assessment of novel analgesics to improve quality of life. C57BL/6 J and DBA/2 J mice received unilateral intraplantar injections of 100% CFA, Paclitaxel, or CCI surgery to compare their distance traveled in a voluntary wheel running assay, paw edema diameter, and mechanical sensitivity. Mechanical withdrawal thresholds were lower in both strains of mice that received CFA when compared to their vehicle. However, a decrease in distance traveled was observed in CFA-treated C57BL/6 J but not DBA/2 J mice. In a separate group, chemotherapy agent paclitaxel 8 mg/kg, i.p. was administered to both strains of mice to induce cause CIPN which was confirmed by lower mechanical thresholds in paclitaxel-treated mice compared to vehicle-treated mice. Only female C57BL/6 J mice showed attenuation of distance traveled following treatment whereas male C57BL/6 J and DBA/2 J mice did not. Lastly, C57BL/6 J mice underwent chronic constriction injury (CCI) or sham surgery to observe the impact of another chronic neuropathic pain model in wheel running assay. CCI mice showed a gradual decrease in mechanical withdrawal threshold and a decrease in distance traveled compared to sham 5 days following the procedure. Comparing these chronic inflammatory and neuropathic pain models in different mouse strains may help us better understand genetic differences underlying pain perception and its impact on reflexive and nonreflexive outcome measures.

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Allodynia and Disability in Migraine: The Mediating Role of Stress.

This study sought to investigate the relationship between allodynia, psychological variables, and disability among individuals with migraine.

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Social burden of people with the migraine diagnosis in Japan: evidence from a population-based cross-sectional survey.

To quantify the social burden among Japanese migraine patients in the context of currently available migraine treatments, by comparison with non-migraine controls, and comparison of migraine patients currently taking prescription medication versus not taking prescription medication.

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Transient loss of interhemispheric functional connectivity following unilateral cortical spreading depression in awake rats.

Growing evidence shows a critical role of network disturbances in the pathogenesis of migraine. Unilateral pattern of neurological symptoms of aura suggests disruption of interhemispheric interactions during the early phase of a migraine attack. Using local field potentials data from the visual and motor cortices, this study explored effects of unilateral cortical spreading depression, the likely pathophysiological mechanism of migraine aura, on interhemispheric functional connectivity in freely behaving rats.

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Intrathecal Morphine in Postoperative Analgesia for Colorectal Cancer Surgery: A Retrospective Study.

Colorectal cancer surgery is commonly performed with adequate analgesia essential for patient recovery. This study assessed the effectiveness of intrathecal morphine and patient-controlled analgesia (ITM + PCA) vs patient-controlled analgesia alone (PCA) for postoperative pain management in colorectal cancer surgery.

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Perspectives on Pain, Engagement in HIV Care, and Behavioral Interventions for Chronic Pain Among Older Sexual Minority Men Living with HIV and Chronic Pain: A Qualitative Analysis.

The transition of HIV from an acute, fatal illness to a chronic health condition has shifted the treatment needs of people living with HIV (PLWH). PLWH, including sexual minority men (SMM), are living longer and are subject to health concerns often associated with aging. A major health concern of older SMM living with HIV who report problematic substance use is chronic pain. This qualitative analysis of 15 one-on-one interviews with older SMM living with HIV and chronic pain aimed to characterize this population's experiences with pain, engagement in HIV care, and problematic substance use. This study was conducted in a community health center in Boston, MA. We also solicited suggestions for preferred intervention strategies.

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The Prevalence of Opioid Analgesic Use in People with Chronic Noncancer Pain: Systematic Review and Meta-Analysis of Observational Studies.

To review studies examining the proportion of people with chronic noncancer pain who report consuming opioids and characteristics associated with their use.

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Feasibility of Auricular Field Stimulation in Fibromyalgia: Evaluation by Functional Magnetic Resonance Imaging, Randomized Trial.

To evaluate the feasibility of recruitment, preliminary efficacy, and acceptability of auricular percutaneous electrical nerve field stimulation (PENFS) for the treatment of fibromyalgia in veterans, using neuroimaging as an outcome measure and a biomarker of treatment response.

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Female Gender Is Associated with a Higher Prevalence of Chronic Neck Pain, Chronic Low Back Pain, and Migraine: Results of the Spanish National Health Survey, 2017.

To assess the prevalence of chronic neck pain (CNP), chronic low back pain (CLBP), and migraine headache (MH) in the Spanish population and to identify sociodemographic and health-related variables associated with CNP, CLBP, and MH.

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