Mol Pain
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Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. ⋯ Multi-coil rTMS may be a safe and effective treatment option for acute as well as for chronic pain, such as that accompanying fibromyalgia. Further studies are necessary to optimize configurations and settings as well as to elucidate the mechanisms that lead to the long-lasting pain control produced by these treatments.
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Bilateral sagittal split ramus osteotomy (BSSRO) is a common orthognatic surgical procedure. Sensory disturbances in the inferior alveolar nerve, including hypoesthesia and dysesthesia, are frequently observed after BSSRO, even without distinct nerve injury. The mechanisms that underlie individual differences in the vulnerability to sensory disturbances have not yet been elucidated. ⋯ The GWAS of sensory disturbances after BSSRO revealed associations between genetic polymorphisms located in the flanking region of the ARID1B and ZPLD1 genes and hypoesthesia and between a nonsynonymous genetic polymorphism in the METTL4 gene and dysesthesia.
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Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. ⋯ The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.
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Opioid receptors regulate a diverse array of physiological functions. Mu opioid receptor agonists are well-known analgesics for treating acute pain. In contrast, animal models suggest that chronic pain is more effectively relieved by delta opioid receptor agonists. A number of studies have shown that chronic pain results in increased function of delta opioid receptors. This is proposed to result from enhanced trafficking of the delta opioid receptor to the cell membrane induced by persistent tissue injury. However, recent studies have questioned this mechanism, which has resulted in some uncertainty as to whether delta opioid receptors are indeed upregulated in chronic pain states. To clarify this question, we have examined the effect of chronic inflammatory pain over time using both an ex vivo measure of delta function: receptor-Ca2+ channel coupling, and an in vivo measure; the relief of chronic pain by a delta opioid receptor agonist. In addition, as beta-arrestin 2 can regulate delta opioid receptor trafficking and signaling, we have further examined whether deleting this scaffolding and signal transduction molecule alters delta opioid receptor function. ⋯ Our results indicate that there is an upregulation of delta opioid receptor function following chronic pain. This gain of function is reflected in the increased efficacy of a delta agonist in both behavioral and electrophysiological measures. Overall, this work confirms that delta opioid receptors can be enhanced following tissue injury associated with chronic pain.
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The TRPV1 ion channel is expressed in nociceptors, where pharmacological modulation of its function may offer a means of alleviating pain and neurogenic inflammation processes in the human body. The aim of this study was to investigate the effects of cholesterol depletion of the cell on ion-permeability of the TRPV1 ion channel. The ion-permeability properties of TRPV1 were assessed using whole-cell patch-clamp and YO-PRO uptake rate studies on a Chinese hamster ovary (CHO) cell line expressing this ion channel. ⋯ Our findings show that cholesterol depletion inhibited both the second current, and the increase in ion-permeability of the TRPV1 channel, resulting from sustained agonist-activation with capsaicin and protons (pH 5.5). These results were confirmed with YO-PRO uptake rate studies using laser scanning confocal microscopy, where cholesterol depletion was found to decrease TRPV1 mediated uptake rates of YO-PRO. Hence, these results propose a novel mechanism by which cellular cholesterol depletion modulates the function of TRPV1, which may constitute a novel approach for treatment of neurogenic pain.