Articles: hyperalgesia.
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1. Gabapentin (neurontin) is a novel antiepileptic agent that binds to the alpha 2 delta subunit of voltage-dependent calcium channels. The only other compound known to possess affinity for this recognition site is the (S)-(+)-enantiomer of 3-isobutylgaba. ⋯ Gabapentin (30-300 mg kg-1) and S-(+)-isobutylgaba (1-100 mg kg-1) showed sedative/ataxic properties only at the highest dose tested in the rota-rod apparatus. 6. Gabapentin (30-300 mg kg-1, s.c.) failed to show an antinociceptive action in transient pain models. It is concluded that gabapentin represents a novel class of antihyperalgesic agents.
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Randomized Controlled Trial Clinical Trial
Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn-induced secondary hyperalgesia in man: a double-blind, cross-over comparison with morphine and placebo.
Effects of morphine and ketamine (NMDA receptor antagonist) on temporally summated pain ('wind-up-like pain') and spatial aspects of secondary hyperalgesia were investigated in 12 healthy volunteers. Hyperalgesia was produced by a local 1 degree burn injury covering 12.5 cm2 on the medial surface of the calf. Primary hyperalgesia was determined by measuring heat pain detection threshold (HPDT) within the site of injury. ⋯ Morphine did not significantly change the size of the area of secondary hyperalgesia and did not affect 'wind-up-like pain'. Ketamine or morphine did not change thermal detection thresholds. We conclude that spatial and temporal mechanisms, underlying secondary hyperalgesia, are mediated by glutamatergic transmission via NMDA receptors.
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Subcutaneous (s.c.) injection of formalin induces a rapid and prolonged hyperalgesia across widespread areas of the body. This hyperalgesic state involves a brain-to-spinal cord pathway, likely arising from the nucleus raphe magnus. The present study examined whether subsequent activation of spinal cord glia may be critical for the hyperalgesic state to be observed in rats. ⋯ Disruption appeared to be selective, as blockade of only select glial products was effective. That is, up to 120 microg of a functional antagonist of tumor necrosis factor-alpha (TNF binding protein) and 5 microl of an antibody against complement-3 produced no statistically reliable reduction in formalin-induced hyperalgesia. Taken together, the present series of experiments suggest an important role for spinal glial cells in the cascade of events that are initiated by descending signals following s.c. administration of formalin.
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Intradermal capsaicin injection in humans results in primary hyperalgesia to heat and mechanical stimuli applied near the injection site, as well as secondary mechanical hyperalgesia (increased pain from noxious stimuli) and mechanical allodynia (pain from innocuous stimuli) in an area surrounding the site of primary hyperalgesia. This study in rats tested the hypothesis that the secondary hyperalgesia and allodynia observed following intradermal injection of capsaicin was dependent upon activation of voltage sensitive calcium channels in the spinal cord. Responses to application of von Frey filaments of 10 mN and 90 mN bending forces were tested in all rats before and after injection of capsaicin into the plantar surface of a hindpaw. ⋯ However, all three blockers dose dependently prevented the development of secondary mechanical hyperalgesia and allodynia. The threshold to mechanical stimulation with von Frey filaments was also increased significantly in animals treated with these calcium channel blockers when compared to articial cerebrospinal fluid control animals. These data suggest that calcium channels are important for the development of mechanical hyperalgesia and allodynia that occurs following capsaicin injection.