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This study aims to evaluate the feasibility and efficacy of a complex health intervention, based on the combination of conventional Western medicine and traditional Chinese medicine (TCM), in an outpatient department of a university hospital for patients with frequent episodic or chronic tension-type headaches.
Learn More >Neuropathic pain is often observed in individuals with multiple sclerosis (MS) and spinal cord injury (SCI) and is not adequately alleviated by current pharmacotherapies. A better understanding of underlying mechanisms could facilitate the discovery of novel targets for therapeutic interventions. We previously reported that decreased plasma membrane calcium ATPase 2 (PMCA2) expression in the dorsal horn (DH) of healthy PMCA2 mice is paralleled by increased sensitivity to evoked nociceptive pain. These studies suggested that PMCA2, a calcium extrusion pump expressed in spinal cord neurons, plays a role in pain mechanisms. However, the contribution of PMCA2 to neuropathic pain processing remains undefined. The present studies investigated the role of PMCA2 in neuropathic pain processing in the DH of wild-type mice affected by experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and following SCI.
Learn More >The intraoperative administration of methadone is effective in reducing postoperative painPreventative analgesic interventions may provide protection against the development of persistent postoperative pain WHAT THIS ARTICLE TELLS US THAT IS NEW: Using data from two previously completed trials, it was observed that a single intraoperative dose of methadone was associated with fewer episodes of pain during the first month after cardiac surgery and the first 3 months after spinal surgeryFewer spine surgery patients who received methadone intraoperatively were receiving opioids 3 months after surgery, suggesting a possible reduction in chronic opioid use BACKGROUND:: Methadone is a long-acting opioid that has been reported to reduce postoperative pain scores and analgesic requirements and may attenuate development of chronic postsurgical pain. The aim of this secondary analysis of two previous trials was to follow up with patients who had received a single intraoperative dose of either methadone or traditional opioids for complex spine or cardiac surgical procedures.
Learn More >Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain.
Learn More >The αδ-1 subunit of voltage-gated calcium channels binds to gabapentin and pregabalin, mediating the analgesic action of these drugs against neuropathic pain. Extracellular matrix proteins from the thrombospondin (TSP) family have been identified as ligands of αδ-1 in the CNS. This interaction was found to be crucial for excitatory synaptogenesis and neuronal sensitisation which in turn can be inhibited by gabapentin, suggesting a potential role in the pathogenesis of neuropathic pain. Here, we provide information on the biochemical properties of the direct TSP/αδ-1 interaction using an ELISA-style ligand binding assay. Our data reveal that full-length pentameric TSP-4, but neither TSP-5/COMP of the pentamer-forming subgroup B nor TSP-2 of the trimer-forming subgroup A directly interact with a soluble variant of αδ-1 (αδ-1). Interestingly, this interaction is not inhibited by gabapentin on a molecular level and is not detectable on the surface of HEK293-EBNA cells over-expressing αδ-1 protein. These results provide biochemical evidence that supports a specific role of TSP-4 among the TSPs in mediating the binding to neuronal αδ-1 and suggest that gabapentin does not directly target TSP/αδ-1 interaction to alleviate neuropathic pain.
Learn More >We aimed to investigate the factors associated with variations in postoperative pain trajectories over time in patients using intravenous patient-controlled analgesia (IV-PCA) for postoperative pain.
Learn More >Headache has emerged as a global public health concern. However, little is known about the burden from headache disorders in China. The aim of this work was to quantify the spatial patterns and temporal trends of burden from headache disorders in China.
Learn More >Piwi-interacting RNA (piRNA) is the largest class of small noncoding RNA and involved in various physiological and pathological processes. However, whether it has a role in pain modulation remains unknown. In the present study, we found that spinal piRNA-DQ541777 (piR-DQ541777) was significantly increased in the male mouse model of sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain. Knockdown of spinal piR-DQ541777 alleviated CCI-induced thermal hyperalgesia and mechanical allodynia and spinal neuronal sensitization. However, overexpression of spinal piR-DQ541777 in naïve mice produced pain behaviors and increased spinal neuron sensitization. Furthermore, we found that piR-DQ541777 regulates pain behaviors by targeting CDK5 regulatory subunit-associated protein 1 (Cdk5rap1). CCI increased the methylation level of CpG islands in the promoter and consequent reduced the expression of Cdk5rap1, which was reversed by knockdown of piR-DQ541777 and mimicked by overexpression of piR-DQ541777 in naïve mice. Finally, piR-DQ541777 increased the methylation level of CpG islands by recruiting DNA methyltransferase 3A (DNMT3a) to promoter. In conclusion, this study represents a novel role of piR-DQ541777 in the regulation of neuropathic pain through methylation of Chronic pain affects approximately 20% of the world's population and is Although we have studied the neurobiological mechanism of neuropathic pain for decades, there is still no ideal drug available to treat it. This work that a novel role of piR-DQ541777 in the regulation of neuropathic pain through methylation of Our findings provide the first evidence of the regulatory effect of piRNAs on neuropathic pain, which may improve our understanding of pain mechanisms and lead to the discovery of novel drug targets for the prevention and treatment of neuropathic pain.
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