Articles: hyperalgesia.
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Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat.
Mechanisms underlying pain in chronic pancreatitis (CP) are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs) were involved in astrocytic activation and pain behavior in CP-induced pain. ⋯ These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.
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Diabetic neuropathy is one of the most common complications of diabetes and causes various problems in daily life. Several investigations have noted that many factors in the spinal cord are involved in the symptoms of painful diabetic neuropathy, and there are very few effective therapeutic regimens. In the present study, we sought to elucidate the role of the RhoA/Rho kinase (ROCK) pathway in thermal hyperalgesia in diabetic mice. ⋯ The expression of eNOS and NO metabolite contents in the spinal cord was decreased in diabetic mice, and these changes were normalized by treatment with simvastatin. The present results show that HMG-CoA reductase inhibitors have an inhibitory effect on thermal hyperalgesia in diabetic mice, which is mediated by an increase in NO production through the inhibition of RhoA/ROCK pathways. These results suggest that ROCK inhibitors and HMG-CoA inhibitors may be attractive compounds to relieve the symptoms of painful diabetic neuropathies.
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Reg Anesth Pain Med · Jan 2011
Effect of continuous posttraumatic intrathecal nocistatin on the development of mechanical allodynia.
The neuropeptide nocistatin has a variety of effects on nociception and other central nervous system functions. It has shown to exert diverging effects on nociceptive behavior in various experimental pain models depending on the dose administered. The inhibitory effect of spinal nocistatin on the release of glycine and γ-aminobutyric acid is thought to be responsible for pronociceptive effects, whereas the antinociceptive action of nocistatin can be attributed to diminished glycine-dependent N-methyl-D-aspartate receptor activation. So far, nocistatin has only been investigated in experimental models of already established pain and has been injected as a bolus. ⋯ Because nocistatin has well-documented effects on established pathological pain, it is conceivable that its effect on nociception is only effective when spinal circuitry is pathologically altered.
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Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using Nav1.9-null mice and Nav1.9 knock-down rats. ⋯ This was correlated with an increase in Nav1.9 immunolabeling in nerve fibers surrounding the inflamed area. No change in Nav1.9 current density could be detected in the soma of retrolabeled DRG neurons innervating inflamed tissues, suggesting that newly produced channels may be non-functional at this level and rather contribute to the observed increase in axonal transport. Our results provide evidence that Nav1.9 plays a crucial role in the generation of heat and mechanical pain hypersensitivity, both in subacute and chronic inflammatory pain models, and bring new elements for the understanding of its regulation in those models.
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This study investigated the role of the cholinergic system in the modulation of inflammatory and neuropathic pain. The paw pressure test was used with inflammatory pain induced by intraplantar injection of carrageenan and neuropathic pain induced by sciatic nerve constriction. All drugs were locally administered into the right hindpaw of rats. ⋯ Atropine significantly decreased the nociceptive threshold only in the treated paw. On the other hand, in the presence of neuropathic pain, atropine (300 μg) did not alter the nociceptive threshold induced by constriction of the sciatic nerve. This study suggests that a peripheral endogenous cholinergic system involving muscarinic receptors may be activated during inflammation as a modulatory negative feedback control of inflammatory pain.