Articles: hyperalgesia.
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The peripheral serotonergic system has been implicated in the modulation of an array of pain states, from migraine to fibromyalgia; however, the mechanism by which serotonin (5HT) induces pain is unclear. Peripherally released 5HT induces thermal hyperalgesia, possibly via modulation of the transient receptor potential V1 (TRPV1) channel, which is gated by various noxious stimuli, including capsaicin. We previously reported in vitro that 5HT increases calcium accumulation in the capsaicin-sensitive population of sensory neurons with a corresponding increase in proinflammatory neuropeptide release, and both are antagonized by pretreatment with 5HT(2A) and 5HT(3) antagonists, as well as the anti-migraine drug sumatriptan. ⋯ We report that 5HT pretreatment enhances TRPV1-evoked thermal hyperalgesia, which is attenuated with local pretreatment with ketanserin, granisetron, or sumatriptan. We also report that peripheral 5HT induced a similar magnitude of thermal hyperalgesia in male and female rats. Overall, our results provide in vivo evidence supporting an enhancing role of 5HT on TRPV1-evoked thermal hyperalgesia, which can be attenuated by peripheral serotonergic intervention.
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Comparative Study
Characterization of oxaliplatin-induced chronic painful peripheral neuropathy in the rat and comparison with the neuropathy induced by paclitaxel.
Anti-neoplastic agents in the platinum-complex, taxane, vinca alkaloid, and proteasome-inhibitor classes induce a dose-limiting, chronic, distal, symmetrical, sensory peripheral neuropathy that is often accompanied by neuropathic pain. Clinical descriptions suggest that these conditions are very similar, but clinical data are insufficient to determine the degree of similarity and to determine if they share common pathophysiological mechanisms. Animal models do not have the limitations of clinical studies and so we have characterized a rat model of chronic painful peripheral neuropathy induced by a platinum-complex agent, oxaliplatin, in order to compare it with a previously characterized model of chronic painful peripheral neuropathy induced by a taxane agent, paclitaxel. ⋯ Single fiber recordings found an abnormal incidence of A- and C-fibers with irregular, low-frequency spontaneous discharge. Prophylactic dosing with two drugs that are known to protect mitochondria, acetyl-l-carnitine and olesoxime, significantly reduced the development of pain hypersensitivity. Our results are very similar to those obtained previously with paclitaxel, and support the hypothesis that these two agents, and perhaps other chemotherapeutics, produce very similar conditions because they have a mitotoxic effect on primary afferent neurons.
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Neuroscience letters · Feb 2012
The beta-lactam antibiotic, ceftriaxone, inhibits the development of opioid-induced hyperalgesia in mice.
The glutamate transporter GLT-1 is primarily responsible for glutamate clearance in the spinal cord. beta-Lactam antibiotics have been shown to attenuate neuropathic pain behaviors by promoting GLT-1 expression and function in the CNS. The present study tested the hypothesis that ceftriaxone, a prototype beta-lactam antibiotic, can prevent the development of opioid-induced hyperalgesia (OIH) in mice. ⋯ Correlating with the behavioral effects, ceftriaxone reversed downregulation of GLT-1 expression that was induced by OIH. These results suggest that ceftriaxone inhibited the development of OIH by up-regulating spinal GLT-1 expression.
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Surgery-induced neuroplasticity at spinal and supra-spinal levels is assumed to evoke a clinical acute post-operative pain (cAPOP) experience, which is expressed by allodynia and/or hyperalgesia. It remains unclear whether the systemic pain perception measured outside the incision area remains unchanged and whether it is affected by the presence of cAPOP. ⋯ This post-surgical allodynia, as reflected by the systemic enhancement of pain perception, may represent plasticity in the central pain pathways at the supra-spinal level. Pre-surgical assessment of a patient's pain perception profile may predict certain pain dimensions of post-surgical pain plasticity. The evaluation of individual pain profiles may contribute to a mechanism-based approach aimed to attenuate the cAPOP.
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Recent studies demonstrated that patients with carpal tunnel syndrome (CTS) have signs of thermal and mechanical hyperalgesia in extra-median territories suggesting an involvement of central pain mechanisms. As previous studies included patients with shoulder/arm symptoms or neck pain, a potential influence of these coexisting disorders cannot be excluded. This study therefore evaluated whether widespread sensory changes (hypoesthesia or hyperalgesia) are present in patients with unilateral CTS in the absence of coexisting disorders. ⋯ This was especially apparent for heat pain ratings which were elevated not only in the affected hand but also in the neck and tibialis anterior muscle. In conclusion, CTS alone in the absence of coexisting neck and arm pain does not account for sensory changes outside the affected hand as determined by traditional QST threshold testing. Elevated pain ratings may however be an early indication of central pain mechanisms.