Articles: hyperalgesia-pathology.
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Accumulating evidence shows that inhibition of glycogen synthase kinase-3beta (GSK-3β) ameliorates cognitive impairments caused by a diverse array of diseases. Our previous work showed that spared nerve injury (SNI) that induces neuropathic pain causes short-term memory deficits. Here, we reported that GSK-3β activity was enhanced in hippocampus and reduced in spinal dorsal horn following SNI, and the changes persisted for at least 45 days. ⋯ Finally, intravenous injection of interleukin-1beta that induces pain hypersensitivity and memory deficits mimicked the SNI-induced the differential regulation of GSK-3β/β-catenin/BDNF in spinal dorsal horn and in hippocampus. Accordingly, the prolonged opposite changes of GSK-3β activity in hippocampus and in spinal dorsal horn induced by SNI may contribute to memory deficits and neuropathic pain by differential regulation of BDNF in the two regions. GSK-3β inhibitors that treat cognitive disorders may result in a long-lasting pain hypersensitivity.
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Neuroscience letters · Nov 2018
A new central post-stroke pain rat model: autologous blood injected thalamic hemorrhage involved increased expression of P2X4 receptor.
Stroke is the leading cause of disability and death in the world. Central post-stroke pain (CPSP), a central neuropathic pain syndrome occurring after cerebral stroke, is a serious problem. But on account of the lack of reliable animal models, the mechanisms underlying CPSP remains poorly understood. ⋯ A significant alleviation of mechanical allodynia was achieved following the administration of adrenergic antidepressants and antiepileptics. Meanwhile, we found a significant decrease in P2 × 4 receptor expression after treatment with these drugs. Taken together, our results suggest that targeting P2 × 4 receptor may be effective in the treatment of CPSP.
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Randomized Controlled Trial
Aδ and not C fibers mediate thermal hyperalgesia to short laser stimuli after burn injury in man.
It remains unclear which nerve fibers are responsible for mediating hyperalgesia after skin injury. Here, we examined the role of Aδ and C fibers in inflammatory hyperalgesia after a first-degree burn injury. A CO2 laser delivered ultrafast short constant-temperature heat pulses to the upper part of the lower leg to stimulate selectively the relatively fast-conducting thinly myelinated Aδ and the slowly conducting unmyelinated C fibers. ⋯ No group differences in C-fiber-mediated sensations were observed. Our findings indicate that quickly adapting Aδ fibers but not quickly adapting C fibers are sensitized when activated by short and ultrafast heat stimuli after skin burn injury. Our results further show that this change occurs between 1 hour and 24 hours after injury and that it does not extend to the skin surrounding the injury.
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Objective Although nociceptive sensitisation is an important pathophysiological process in migraine and migraine chronification, its underlying mechanisms remain unclear. Toll-like receptor 4 (TLR4), a pattern-recognition molecule, has a critical role in both neuropathic pain and morphine tolerance. The present study examined whether elements of the TLR4 pathway contribute to hyperalgesia induced by dural inflammation in rats. ⋯ The inflammatory soup stimulus increased the production of TLR4 downstream molecules and interleukin-1 beta. Higher levels of microglia activation and brain-derived neurotrophic factor release were observed following the administration of the inflammatory soup but were alleviated by TAK-242. Conclusions These data suggest that the TLR4 signalling pathway promotes hyperalgesia induced by acute inflammatory soup delivery by stimulating the production of proinflammatory cytokines and activating microglia.
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Chronic pain induced by nerve damage due to trauma or invasion of cancer to the bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely reflecting adaptive changes within central circuits that amplify nociceptive signals. The present study explored the possible contribution of the mesolimbic dopaminergic circuit in promoting allodynia related to neuropathic and cancer pain. Mice with ligation of the sciatic nerve or treated with intrafemoral osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on the injured side. ⋯ Optogenetic activation of these cells produced a significant but transient anti-allodynic effect in nerve injured or tumor-bearing mice without increasing response thresholds to thermal stimulation in sham-operated animals. Suppressed activity of mesolimbic dopaminergic neurons is likely to contribute to decreased inhibition of N. Acc. output neurons and to neuropathic or cancer pain-induced allodynia suggesting strategies for modulation of pathological pain states.