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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.
Learn More >Chronic pain often occurs in the elderly, particularly in the patients with neurodegenerative disorders such as Alzheimer's disease (AD). Although studies indicate that chronic pain correlates with cognitive decline, it is unclear whether chronic pain accelerates AD pathogenesis. In this review, we provide evidence that supports a link between chronic pain and AD and discuss potential mechanisms underlying this connection based on currently available literature from human and animal studies. Specifically, we describe two intertwined processes, locus coeruleus noradrenergic system dysfunction and neuroinflammation resulting from microglial pro-inflammatory activation in brain areas mediating the affective component of pain and cognition that have been found to influence both chronic pain and AD. These represent a pathological overlap that likely leads chronic pain to accelerate AD pathogenesis. Further, we discuss potential therapeutic interventions targeting noradrenergic dysfunction and microglial activation that may improve patient outcomes for those with chronic pain and AD.
Learn More >This study assessed the participation of spinal TWIK-related acid-sensitive K channels 1 and 3 (TASK-1 and TASK-3) in inflammatory (formalin test) and neuropathic (spinal nerve ligation, SNL) pain in rats. Intrathecal pre-treatment (-10 min) with the TASK-1 blocker ML365 or TASK-3 blocker PK-THPP, but not vehicle, enhanced in a dose-dependent manner 1% formalin-induced acute and long-lasting secondary mechanical allodynia and mechanical hyperalgesia in rats. In contrast, intrathecal pre-treatment with terbinafine, an activator of TASK-3, reduced formalin-induced flinching and allodynia/hyperalgesia. Both blockers and terbinafine had similar effects on female and male rats. In addition, intrathecal injection of ML365 or PK-THPP blocked the terbinafine-induced antiallodynic effect in neuropathic rats, but they did not modify baseline withdrawal threshold in naïve or sham-operated rats. TASK-1 and TASK-3 mRNA and protein were expressed in L4 and L5 dorsal root ganglia (DRG) and dorsal and ventral spinal cord of naïve animals. Interestingly, formalin injection increased TASK-1 expression in ipsilateral L5 DRG, but not in the spinal cord. Moreover, formalin injection transiently enhanced TASK-3 expression in ipsilateral L5 DRG and dorsal spinal cord. In contrast, SNL down-regulated TASK-3 expression in the ipsilateral L4 and L5 DRG but not in dorsal or ventral spinal cord, while SNL did not modify TASK-1 expression at any tissue. The pharmacological and molecular results suggest that TASK-1 and TASK-3 have a relevant antinociceptive role in inflammatory and neuropathic pain.
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