Nicotinic receptors have been found to play a role in modulating pain transmission in the CNS. Activation of cholinergic pathways by nicotine and nicotinic agonists has been shown to elicit antinociceptive effects in a variety of species and pain tests. The involvement of α 7 nicotinic receptors in nicotinic analgesia was assessed after spinal (i.t.) and intraventricular (i.c.v.) administration in mice. Dose-dependent antinociceptive effects were seen with the α 7 agonist choline after spinal and supraspinal injection using the tail-flick test. Furthermore, α 7 antagonists MLA and α-BGTX significantly blocked the effects of choline. Dihydro-β-erythroidine and mecamylamine failed to block choline-induced antinociception. These results strongly support the involvement of α 7 subunits in choline's antinociceptive effects. DMXB and 4-OH-DMXB, partial α 7 agonists, failed to elicit a significant antinociceptive effect. However, they blocked choline-induced antinociception in a dose-dependent manner following i.t. injection. This antagonism is probably related to their partial agonistic properties of the α 7 receptors. These studies suggest that activation of α 7 receptors in the CNS elicits antinociceptive effects in an acute thermal pain model.