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Deficiency of glucagon gene-derived peptides induces peripheral polyneuropathy in mice.

Although diabetic polyneuropathy (DPN) is the commonest diabetic complication, its pathology remains to be clarified. As previous papers have suggested the neuroprotective effects of glucagon-like peptide-1 in DPN, the current study investigated the physiological indispensability of glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1 in the peripheral nervous system (PNS). Neurological functions and neuropathological changes of GCGDP deficient (gcg-/-) mice were examined. The gcg-/- mice showed tactile allodynia and thermal hyperalgesia at 12-18 weeks old, followed by tactile and thermal hypoalgesia at 36 weeks old. Nerve conduction studies revealed a decrease in sensory nerve conduction velocity at 36 weeks old. Pathological findings showed a decrease in intraepidermal nerve fiber densities. Electron microscopy revealed a decrease in circularity and an increase in g-ratio of myelinated fibers and a decrease of unmyelinated fibers in the sural nerves of the gcg-/- mice. Effects of glucagon on neurite outgrowth were examined using an ex vivo culture of dorsal root ganglia. A supraphysiological concentration of glucagon promoted neurite outgrowth. In conclusion, the mice with deficiency of GCGDPs developed peripheral neuropathy with age. Furthermore, glucagon might have neuroprotective effects on the PNS of mice. GCGDPs might be involved in the pathology of DPN.

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Discovery of ACE2 receptors for SARS-CoV-2 (COVID-19) on peripheral small-fiber sensory neurons of uncertain clinical significance.

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Exploring Factors Associated with Long-Term Opioid Therapy in Cancer Survivors:An Integrative Review.

The prevalence of chronic pain in cancer survivors is double that of the general US population. Opioids have been the foundation of cancer pain management for decades; however, there is a paucity of literature on long-term opioid therapy (LTOT) in cancer survivors. An understanding of factors related to LTOT use in cancer survivors is needed to address chronic pain and balance opioid harms in the expanding population of cancer survivors.

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Mesocorticolimbic monoamines in a rodent model of chronic neuropathic pain.

Chronic pain manifests in multiple disorders and is highly debilitating. While its pathophysiology is not fully understood, the involvement of the mesocorticolimbic monoaminergic systems have been shown to play a critical role in chronic pain emergence and/or maintenance. In this study, we analyzed the levels of monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in mesocorticolimbic areas – medial prefrontal cortex, orbitofrontal cortex, striatum, nucleus accumbens and amygdala – 1 month after a neuropathic lesion, Spared Nerve Injury (SNI). In SNI animals, were observed a marginal decrease of DA and 5-HT in the striatum and a rightward shift in the levels of NA in the nucleus accumbens. While mesocorticolimbic monoamines might be relevant for chronic pain pathophysiology its content appears to be relatively unaffected in our experimental conditions.

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Multimodal physical therapy versus topical lidocaine for provoked vestibulodynia: a prospective, multicentre, randomized trial.

Provoked vestibulodynia is the most common subtype of chronic vulvar pain. This highly prevalent and debilitating condition is characterized by acute recurrent pain located at the entry of the vagina in response to pressure application or attempted vaginal penetration. Physical therapy is advocated as a first-line treatment for provoked vestibulodynia but evidence supporting its efficacy is scarce.

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Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS): Bayesian Adaptive Comparative Effectiveness Randomized Trial.

Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers. There are no comparative studies that identify the most effective medication for pain reduction in CSPN.

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Association between frailty and chronic pain among older adults: a systematic review and meta-analysis.

Frailty and chronic pain are prevalent among older adults. However, no study has systematically reviewed the association between frailty and chronic pain in older adults. Therefore, we aimed to estimate the prevalence of frailty and prefrailty among older adults with chronic pain and review the longitudinal association between frailty status and chronic pain.

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A prospective observational study on trajectories and prognostic factors of mid back pain.

Although mid back pain (MBP) is a common condition that causes significant disability, it has received little attention in research and knowledge about trajectories and prognosis of MBP is limited. The purpose of this study was to identify trajectories of MBP and baseline risk factors for an unfavorable outcome in MBP patients undergoing chiropractic treatment.

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Effect of KATP channel blocker glibenclamide on levcromakalim-induced headache.

Administration of ATP-sensitive potassium channel opener levcromakalim triggers headache in healthy volunteers and migraine attacks in migraine patients. Here, we investigated the effect of ATP-sensitive potassium channel blocker glibenclamide on levcromakalim-induced headache in healthy volunteers.

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Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts.

To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions.

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