Articles: hyperalgesia.
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Joint mobilization is a treatment approach commonly used by physical therapists for the management of a variety of painful conditions. However, the clinical effectiveness when compared to placebo and the neurophysiological mechanism of action are not known. The purpose of this study was to establish that application of a manual therapy technique will produce antihyperalgesia in an animal model of joint inflammation and that the antihyperalgesia produced by joint mobilization depends on the time of treatment application. ⋯ Both 9 and 15 min of mobilization, but not 3 min of mobilization, increased the withdrawal threshold to mechanical stimuli to baseline values when compared with control groups. The antihyperalgesic effect of joint mobilization lasted 30 min. Thus, joint mobilization (9 or 15 min duration) produces a significant reversal of secondary mechanical hyperalgesia induced by intra-articular injection of capsaicin.
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The clinical use of the antineoplastic agent paclitaxel (Taxol) is significantly limited in its effectiveness by a dose-related painful peripheral neuropathy. To evaluate underlying mechanisms, we developed a model of Taxol-induced painful peripheral neuropathy in the rat and determined the involvement of two second messengers that contribute to enhanced nociception in other models of inflammatory and neuropathic pain, protein kinase Cepsilon and protein kinase A. Taxol administered acutely, or chronically over 12 days, produced a decrease in mechanical nociceptive threshold. ⋯ Mechanical allodynia and thermal hyperalgesia were also present in Taxol-treated rats. Hyperalgesia, produced by both acute and chronic Taxol, was attenuated by intradermal injection of selective second messenger antagonists for protein kinase Cepsilon and protein kinase A. These findings provide insight into the mechanism of Taxol-induced painful peripheral neuropathy that may help control side effects of chemotherapy and improve its clinical efficacy.
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The heat--capsaicin sensitization model was developed as a noninvasive and noninjurious human experimental pain model. The sequential application of moderate intensity thermal and topical chemical stimuli produces stable and long-lasting areas of cutaneous secondary hyperalgesia. The aim of the present study was to validate the heat--capsaicin sensitization model as a tool for testing analgesic drug efficacy. Responsivity of model-associated measures was tested with remifentanil, a potent and ultrashort acting mu-opioid agonist. ⋯ Using the heat-capsaicin sensitization model, opioid analgesia and suppression of secondary hyperalgesia was reliably demonstrated without skin injury.
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A growing body of evidence supports a nicotinic cholinergic approach to pain management, as neuronal nicotinic receptor agonists have shown efficacy across animal models of both inflammatory and neuropathic pain. However, most of these investigations have focused on the spinal system, and there is to date no report of nicotinic receptor-mediated antinociception in any pain model involving the trigeminal field of innervation. Thus, the purpose of the present studies was to evaluate whether the neuronal nicotinic receptor agonist epibatidine possesses antihyperalgesic activity in the formalin model of facial pain. ⋯ Finally, pretreatment with the selective neuronal nicotinic receptor antagonist mecamylamine completely abolished the antihyperalgesic effect of epibatidine in both phases. Taken together, these studies demonstrate that in both the acute and tonic phases of the formalin model of facial pain, epibatidine produces a neuronal nicotinic receptor-mediated antihyperalgesia that is both dose- and time-dependent. These results support the rationale for exploring the clinical efficacy of nicotinic agonists as analgesics to treat certain types of trigeminal pain in humans.
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Selection line rats congenitally high or low for autotomy in the neuroma model of neuropathic pain (HA and LA rats) were found to be correspondingly high and low in a second type of neuropathic pain, the Chung model, which employs an alternative phenotypic endpoint, tactile allodynia. It has been proposed that both phenotypes reflect ectopic hyperexcitability in axotomized primary sensory neurons. ⋯ However, in the one neuronal subclass previously linked to neuropathic pain in these models the increase was significantly greater in HA than LA rats, and only at the time when pain scores in the two lines were diverging. Heritable differences in electrical response to axotomy in a specific afferent cell type appear to be a fundamental determinant of neuropathic pain.