Articles: hyperalgesia.
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Inflammation modifies the input-output properties of peripheral nociceptive neurons such that the same stimulus produces enhanced nociceptive firing. This increased nociceptive output enters the superficial dorsal spinal cord (SDH), an intricate neuronal network composed largely of excitatory and inhibitory interneurons and a small percentage of projection neurons. The SDH network comprises the first central nervous system network integrating noxious information. ⋯ We further demonstrate that an increase in afferent activity mimics the response of the SDH network to noxious heat stimuli under inflammatory conditions. Using a computational model of the SDH network, we predict that the changes in SDH network activity result in overall increased activity of excitatory neurons, amplifying the output from SDH to higher brain centers. We suggest that during acute local peripheral inflammation, the SDH network undergoes dynamic changes promoting hyperalgesia.
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Background: Remifentanil-induced postoperative hyperalgesia (RIH) refers to a state of hyperalgesia or aggravated pre-existing pain after remifentanil exposure. There has been considerable interest in understanding and preventing RIH. However, the mechanisms responsible for RIH are still not completely understood. ⋯ In addition, TRPA1 antagonist HC-030031 also alleviated mechanical pain and decreased TRPA1 expression in RIH without affecting TLR4 signaling in DRG. Conclusions: Taken together, these results suggested that activation of TLR4 signaling pathway engaged in the development of RIH by regulating TRPA1 in DRG neurons. Blocking TLR4 and TRPA1 might serve as a promising therapeutic strategy for RIH.
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Allodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism-based treatment strategies. ⋯ This study provides clinical evidence that autonomic measures to noxious stimuli can objectively detect sensitization processes along the nociceptive neuraxis in complex regional pain syndrome (CRPS) (e.g. widespread hyperexcitability). Pain-autonomic readouts may represent valuable tools to explore pathophysiological mechanisms in a variety of pain patients and offer novel avenues to help guide mechanism-based therapeutic strategies.
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Resolvin D1 (RvD1) suppresses inflammatory, postoperative, and neuropathic pain. The present study assessed the roles and mechanisms of RvD1 in mechanical allodynia after burn injury. A rat model of burn injury was established for analyses, and RvD1 was injected intraperitoneally. ⋯ In addition, inhibition of p38 MAPK prevented spinal microglial activation and downregulated BDNF/TrkB following burn injury. Furthermore, inhibition of BDNF/TrkB signaling prevented spinal microglial activation and downregulated p-p38 MAPK within spinal microglia. Taken together, this study demonstrated that RvD1 might attenuate mechanical allodynia after burn injury by inhibiting spinal cord glial activation, microglial p38 MAPK, and BDNF/TrkB signaling in the spinal dorsal horn.
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Chronic pain, along with comorbid psychiatric disorders, is a common problem worldwide. A growing number of studies have focused on non-opioid-based medicines, and billions of funds have been put into digging new analgesic mechanisms. Peripheral inflammation is one of the critical causes of chronic pain, and drugs with anti-inflammatory effects usually alleviate pain hypersensitivity. ⋯ SRI treatment significantly decreased pro-inflammatory factors release after LPS stimuli in microglia. Three days of SRI treatment relieved CFA-induced mechanical hypersensitivity and anxiety-like behavior, and recovered abnormal neuroplasticity in the anterior cingulate cortex of mice. Therefore, SRI may be a candidate compound for the treatment of chronic inflammatory pain and may serve as a structural basis for the development of new drugs.