The antinociceptive effects of alpha 7 nicotinic agonists in an acute pain model

• Published in: Neuropharmacology 2000-10, Vol.39 (13), p.2785-2791
• Main Authors: Damaj, MI, Meyer, E M, Martin, B R
• Format: Article
• Language: English
• ISSN: 0028-3908
• DOI: 10.1016/S0028-3908(00)00139-8

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 alpha sub(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 alpha sub(7) agonist choline after spinal and supraspinal injection using the tail-flick test. Furthermore, alpha sub(7) antagonists MLA and alpha -BGTX significantly blocked the effects of choline. Dihydro- beta -erythroidine and mecamylamine failed to block choline-induced antinociception. These results strongly support the involvement of alpha sub(7) subunits in choline's antinociceptive effects. DMXB and 4-OH-DMXB, partial alpha sub(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 alpha sub(7) receptors. These studies suggest that activation of alpha sub(7) receptors in the CNS elicits antinociceptive effects in an acute thermal pain model.