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ANALGESIA

The Antinociceptive Response to Nicotinic Agonists in a Mouse Model of Postoperative Pain

From the Department of Anesthesiology, Columbia University, New York City, New York.

Address correspondence and reprint requests to Dr. Pamela Flood, Associate Professor, Department of Anesthesiology, Columbia University, 630 West 168th St., New York City, NY 10032. Address e-mail to pdf3{at}columbia.edu.

Abstract

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 4β2 and 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 4β2 and 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 (4β2 selective) were fully effective as an analgesic in heat and pressure testing. The 7 partial agonist GTS-21 significantly increased the heat latency after surgery, but did not alter pressure threshold. The 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 4β2 and 7 nicotinic-mediated antinociceptive actions.

This article has been cited by other articles:

				L. C. Olson, D. Hong, J. S. Conell-Price, S. Cheng, and P. Flood A Transdermal Nicotine Patch Is Not Effective for Postoperative Pain Management in Smokers: A Pilot Dose-Ranging Study Anesth. Analg., December 1, 2009; 109(6): 1987 - 1991. [Abstract] [Full Text] [PDF]

				N. L. Benowitz Nicotine and Postoperative Management of Pain Anesth. Analg., September 1, 2008; 107(3): 739 - 741. [Full Text] [PDF]