Nicotinic cholinergic receptors: potential targets for inflammatory pain relief

We have shown previously that the development of hyperalgesia and inflammat ion associated with knee joint arthritis depends on interactions among vari ous receptors in the central and peripheral nervous system in addition to t he contribution of blood borne inflammatory mediators. In the present study , the involvement of spinal nicotinic cholinergic receptors in the modulati on of inflammatory pain was evaluated using a model of acute arthritis in r ats. Epibatidine (EP), a potent agonist for neuronal nicotinic acetylcholin e receptors sharing similar structural and functional characteristics with acetylcholine and nicotine, has been used in this study. The physiological effects of EP on pain-related behaviors and inflammation were tested after administration to the dorsal horn via a microdialysis fiber. Knee joint inf lammation was induced in rats by injecting a mixture of kaolin and carragee nan into the knee joint. Paw withdrawal latency to radiant hear was measure d before and at 4, 5, 6, 7 and 8 h after induction of inflammation. The dec rease in PWL in this arthritis model is indicative of secondary hyperalgesi a. The extent of peripheral inflammation was also assessed by measuring kne e joint circumference and temperature. Treatment of the spinal cord of anim als with EP prior to induction of arthritis attenuated the development of h eat hyperalgesia and resulted in a significant improvement of the animals' spontaneous pain-related behaviors. More interestingly, the knee joint circ umference and temperature of these animals were also significantly lower th an those of the control animals when measured at 8 h. Likewise, spinal admi nistration of epibatidine after the: development of hyperalgesia not only s ignificantly attenuated the: decrease in PWL, but prevented further increas es in knee joint swelling and temperature. The antinociceptive effect of ep ibatidine was selectively blocked by the nicotinic receptor antagonist, mec amylamine. Joint circumference and temperature were not selectively altered by mecamylamine suggesting another mechanism involving non-nicotinic recep tors in the spinal regulation of joint inflammatory responses. Collectively , these findings provide considerable evidence to suggest an important role for central nicotinic cholinergic receptors in the modulation of persisten t pain and neurogenic inflammation mediated by events in the dorsal horn. ( C) 1999 International Association for the Study of Pain. Published by Elsev ier Science B.V.