The antinociceptive effects of alpha7 nicotinic agonists in an acute pain model.
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(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(7) agonist choline after spinal and supraspinal injection using the tail-flick test. Furthermore, alpha(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(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 following i.t. injection. This antagonism is probably related to their partial agonistic properties of the alpha(7) receptors. These studies suggest that activation of alpha(7) receptors in the CNS elicits antinociceptive effects in an acute thermal pain model.
Damaj
M I
MI
Department of Pharmacology and Toxicology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0613, USA. mdamaj@hsc.vcu.edu
Meyer
E M
EM
Martin
B R
BR
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D002038:Bungarotoxins / Q000008:administration & dosage / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000700:Analgesics; D001597:Benzylidene Compounds; D002038:Bungarotoxins; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008464:Mecamylamine; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D002794:Choline