Pain
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We assessed whether intrathecal administration of the uncompetitive and competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could produce differential modulation on chemical and mechanical nociception in normal and monoarthritic rats. In addition, the antinociceptive interaction of ketamine and (+/-)CPP on monoarthritic pain was also studied using isobolographic analysis. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. ⋯ Irrespective of the nociceptive test employed, both antagonists showed greater antinociceptive activity in monoarthritic than in healthy rats. Combinations produced synergy of a supra-additive nature in the capsaicin test, but only additive antinociception in paw pressure testing. The efficacy of the drugs, alone or combined, is likely to depend on the differential sensitivity of tonic versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.
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Comparative Study
Activation of the 5-HT1B/D receptor reduces hindlimb neurogenic inflammation caused by sensory nerve stimulation and capsaicin.
Activation of the 5-HT(1B/D) receptor inhibits cerebrovascular neurogenic inflammation (NI). The aim of this study was to determine if the 5-HT(1B/D) receptor agonist sumatriptan can also inhibit NI in other regions of the body. NI was assessed by measuring plasma extravasation (PE) and changes in blood flow in the rat hindpaw. ⋯ The systemic and local inhibitory actions of sumatriptan are mediated by the 5-HT(1B/D) receptor as pre-treatment with the 5-HT(1B/D) antagonist GR127935 (GR; 15 microl, 1 microM, s.c. or 0.2 micromol/kg, i.v.) completely blocked the inhibitory effect of sumatriptan on capsaicin-induced vasodilation and reduced the inhibitory effect of sumatriptan on capsaicin and electrically induced-PE. Neither PE induced by local injection of substance P (SP) (20 pmol, 20 microl, s.c.) nor vasodilation induced by local CGRP injection was affected by pre-treatment with sumatriptan. These findings indicate that both local and systemic activation of the 5-HT(1B/D) receptor by sumatriptan reduce NI induced by nerve stimulation or capsaicin presumably by inhibiting neuropeptide release. 5-HT(1B/D) receptor agonists may be useful for the treatment of non-trigeminal pain conditions involving NI.