The antinociceptive effects of alpha 7 nicotinic agonists in an acute painmodel

Nicotinic receptors have been found to play a role in modulating pain trans mission in the CNS. Activation of cholinergic pathways by nicotine and nico tinic agonists has been shown to elicit antinociceptive effects in a variet y of species and pain tests. The involvement of alpha (7) nicotinic recepto rs in nicotinic analgesia was assessed after spinal (i.t.) and intraventric ular (i.c.v.) administration in mice. Dose-dependent antinociceptive effect s were seen with the alpha (7) agonist choline after spinal and supraspinal injection using the tail-flick test. Furthermore, alpha (7) antagonists ML A and alpha -BGTX significantly blocked the effects of choline. Dihydro-bet a -erythroidine and mecamylamine failed to block choline-induced antinocice ption. These results strongly support the involvement of alpha (7) subunits in choline's antinociceptive effects. DMXB and 4-OH-DMXB, partial alpha (7 ) agonists, failed to elicit a significant antinociceptive effect. However, they blocked choline-induced antinociception in a dose-dependent manner fo llowing i.t. injection. This antagonism is probably related to their partia l agonistic properties of the alpha (7) receptors. These studies suggest th at activation of alpha (7) receptors in the CNS elicits antinociceptive eff ects in an acute thermal pain model. (C) 2000 Elsevier Science Ltd. All rig hts reserved.