Articles: hyperalgesia.
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Two established phenomena contribute to the generation of post-injury pain hypersensitivity: peripheral sensitization, an increase in transduction sensitivity of high threshold A delta and C-fibre nociceptors, and central sensitization, an increase in excitability of neurones in the spinal cord triggered exclusively by C-fibre inputs. We now describe a novel phenomenon: progressive tactile hypersensitivity, which contributes to a cumulative allodynia during inflammation. Behavioural measurements in conscious intact animals showed that repeated light touch stimuli delivered at 5-min intervals to an inflamed paw, established 48 h earlier by an intra-plantar injection of complete Freund's adjuvant (CFA), resulted in a progressive reduction in the mechanical withdrawal threshold by more than 75%, from its already hypersensitive basal level. ⋯ Progressive hypersensitivity, measured here as a progressive tactile allodynia after inflammation in either intact or decerebrate-spinal rats, with its gradual build-up and contribution from A beta fibres, is very different from the central sensitization induced by C-fibre stimulation which is characterised by a peak increase in excitability soon after the conditioning input followed by a steady decrement to baseline levels. Progressive hypersensitivity is likely to be the consequence of an alteration in the function and phenotype of afferents innervating inflamed tissue and the pattern of excitation they produce in spinal neurones. The phenomenon may have an important role in the development of inflammatory pain and hypersensitivity.
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Neuroscience letters · Aug 1996
Clinical TrialTopical acetylsalicylate attenuates capsaicin induced pain, flare and allodynia but not thermal hyperalgesia.
The effect of acetylsalicylic acid (ASA) on capsaicin-evoked activation of cutaneous nociceptors was tested in a double blind study in 10 volunteers. Capsaicin (2% in ethanol) was applied topically for 30 min. ⋯ In contrast, capsaicin-induced heat hyperalgesia was unaffected by ASA. It is concluded that ASA counteracts the excitatory effects of capsaicin on nociceptors and mechanical hyperalgesia but not its sensitizing action to heat.
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A chronic allodynia-like response to mechanical stimulation was observed in rats after severe spinal cord ischemia. This allodynia-like response was not relieved by most conventional analgesics used for treating chronic neuropathic pain. The present experiments evaluated the effects of systemically administered excitatory amino acid receptor antagonists, including the non-competitive N-methyl-D-aspartate (NMDA) receptor/channel blockers MK-801 and dextromethorphan, the competitive NMDA receptor antagonist CGS 19755 and a competitive antagonist of the alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptor NBQX, on the chronic allodynia-like response in spinally injured rats. ⋯ It is concluded that systemic NMDA, but not AMPA, receptor antagonists may have an analgesic effect upon the chronic allodynia-like response. However, the analgesic effect of all NMDA antagonists was associated with side effects. Dextromethorphan, which is clinically tolerated and produced less side effects, may be useful for treating chronic pain associated with central nervous system injury.
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Behavioral and electrophysiological methods were used to investigate the hyperalgesia and allodynia, and functional changes in lumbar spinal dorsal horn neurons, in a model of neuropathic pain (Selzer et al. 1990) involving ligation of one-third to one-half of one sciatic nerve in rats. One and 5 weeks following ligation, there was a significant reduction in hind limb withdrawal latency to noxious radiant heat on the operated side and, to a lesser degree, on the unoperated side. By 16 weeks, heat withdrawal latencies were reduced about equally (approximately 40%) on both sides. ⋯ Mechanical receptive field areas were not significantly different between ipsi- and contralateral sides in the sham and 5-week post-ligation groups, or between sham and 5-week post-ligation groups. However, receptive field areas were significantly larger in the 16-week post-ligation group (both ipsi- and contralateral to ligation) compared to sham and 5-week post-ligation groups. The results suggest that allodynia may be associated with a chronic enhancement of neuronal mechanosensitivity, but that the thermal hyperalgesia is not associated with enhanced neuronal responsiveness or force of withdrawal.
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Treatment of adult rats with a single dose of nerve growth factor (NGF, 1 mg/kg, i.p.) results in a prolonged hypersensitivity to noxious thermal stimulation which becomes noticeable within 30 min of administration and lasts for several days. A significant mechanical hyperalgesia develops within 7 h following injection of NGF and persists for up to 7 days. In the present set of experiments we describe certain quantitative features of this hyperalgesia. ⋯ Injection of the neurokinin NK1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 one day after NGF both induced a transient block of NGF-induced thermal hyperalgesia indicating a non-specific effect rather than an action at NK1 receptors. This was confirmed by finding no reversal of NGF-induced hyperalgesia by RP67580, another NK1 receptor blocker. These results suggest upregulation and activation of BK1 but not NK1 receptors as an additional, probably peripheral, mechanism for the late phase of NGF-induced thermal hyperalgesia.