The antinociceptive response to nicotinic agonists in a mouse model of postoperative pain.
BACKGROUND
Nicotine, the prototypical broad spectrum agonist at central nicotinic receptors, has analgesic action after surgery. Various subtype-specific nicotinic agonists have antinociceptive effects in animal models, but the response is highly dependent on the model tested. In an effort to determine what nicotinic subtypes might be targeted in future clinical studies, we tested agonists selective for alpha 4 beta 2 and alpha 7 containing nicotinic receptors in a mouse model of postoperative pain.


METHODS
After paw incision, mice were tested for heat latency and pressure threshold before and after treatment with a dose range of ligands selective for alpha 4 beta 2 and alpha 7 containing nicotinic receptors. To demonstrate that nicotine reduced nociceptive input in this model, the lumbar spinal cords of a subgroup of these mice were stained for the phosphorylated form if CREB.


RESULTS
Nicotine and metanicotine (alpha 4 beta 2 selective) were fully effective as an analgesic in heat and pressure testing. The alpha 7 partial agonist GTS-21 significantly increased the heat latency after surgery, but did not alter pressure threshold. The alpha 7 selective antagonist methyllicaconitine decreased the efficacy of nicotine to increase heat latency but did not affect pressure threshold. The number of cells in the superficial dorsal horn with nuclei that stained for pCREB was double on the surgical side and the ratio was reduced by nicotine in a dose-dependent manner.


CONCLUSIONS
Our findings suggest that nicotine reduced nociceptive input to the superficial and deep dorsal horn. It also provides support for alpha 4 beta 2 and alpha 7 nicotinic-mediated antinociceptive actions.
Rowley
Thomas J
TJ
Department of Anesthesiology, Columbia University, 630 West 168th St., New York NY 10032, USA.
Payappilly
James
J
Lu
Jeffery
J
Flood
Pamela
P
D000700:Analgesics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D005260:Female; D007530:Isoflurane / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D009538:Nicotine / Q000031:analogs & derivatives / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010149:Postoperative Pain / Q000188:drug therapy* / Q000473:pathology; D011312:Pressure; D013116:Spinal Cord / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D000700:Analgesics; D018685:Anesthetics, Inhalation; D008024:Ligands; D018722:Nicotinic Agonists; C012419:metanicotine; D009538:Nicotine; D007530:Isoflurane; D010100:Oxygen