Pain
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Recent research suggests that exercise can be effective in reducing pain in animals and humans with neuropathic pain. To investigate mechanisms in which exercise may improve hyperalgesia associated with prediabetes, C57Bl/6 mice were fed either standard chow or a high-fat diet for 12 weeks and were provided access to running wheels (exercised) or without access (sedentary). The high-fat diet induced a number of prediabetic symptoms, including increased weight, blood glucose, and insulin levels. ⋯ These results confirm that elevated hypersensitivity and associated neuropathic changes can be induced by a high-fat diet and exercise may alleviate these neuropathic symptoms. These findings suggest that exercise intervention could significantly improve aspects of neuropathy and pain associated with obesity and diabetes. Additionally, this work could potentially help clinicians determine those patients who will develop painful versus insensate neuropathy using intraepidermal nerve fiber quantification.
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Although feverfew has been used for centuries to treat pain and headaches and is recommended for migraine treatment, the mechanism for its protective action remains unknown. Migraine is triggered by calcitonin gene-related peptide (CGRP) release from trigeminal neurons. Peptidergic sensory neurons express a series of transient receptor potential (TRP) channels, including the ankyrin 1 (TRPA1) channel. ⋯ This effect of parthenolide abrogates nociceptive responses evoked by stimulation of peripheral trigeminal endings. TRPA1 targeting and neuronal desensitization by parthenolide inhibits CGRP release from trigeminal neurons and CGRP-mediated meningeal vasodilatation, evoked by either TRPA1 agonists or other unspecific stimuli. TRPA1 partial agonism, together with desensitization and nociceptor defunctionalization, ultimately resulting in inhibition of CGRP release within the trigeminovascular system, may contribute to the antimigraine effect of parthenolide.
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We conducted a postal survey to assess the prevalence and characteristics of neuropathic pain and migraine in a cohort of multiple sclerosis (MS) patients. Of the 1300 questionnaires sent, 673 could be used for statistical analysis. Among the respondents, the overall pain prevalence in the previous month was 79%, with 51% experiencing pain with neuropathic characteristics (NCs) and 46% migraine. ⋯ Migraine, but not NC pain, was associated with age, disease duration, relapsing-remitting course, and interferon-beta treatment. This suggests that NC pain and migraine are mediated by different mechanisms. Therefore, pain mechanisms that specifically operate in MS patients need to be characterized to design optimal treatments for these individuals.
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Scientific evidence support the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. ⋯ Also, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex.
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Randomized Controlled Trial Comparative Study
Intradialytic clearance of opioids: Methadone versus hydromorphone.
Opioids are commonly prescribed to patients with chronic pain associated with end-stage renal disease requiring hemodialysis. The stability of opioid analgesia during dialysis may vary among different opioids. No studies to date have corroborated this clinical observation by directly comparing plasma concentrations of different opioids during dialysis. ⋯ There were no differences between the 2 opioid groups in pain scores, side effect profile, and quality of life. Methadone therapy was not associated with an increased rate of adverse events. If confirmed by larger clinical studies, methadone could be considered as one of the opioids of choice in dialysis patients.