Effect of AMG0347, a Transient Receptor Potential Type V1 Receptor Antagonist, and Morphine on Pain Behavior after Plantar Incision

Abstract

Studies on postoperative pain examine the etiology of incisional pain with the goal to develop new treatments for patients' pain after surgery. The current study examined the analgesic effects of a recently developed transient receptor potential vanilloid 1 (TRPV1) antagonist, AMG0347, on incisional pain in rats. Doses of morphine lower than those used in most rodent studies were also examined. Adult Sprague-Dawley rats were underwent plantar incision. The effect of either AMG0347 or morphine was tested for its effects on guarding pain score, heat withdrawal latency, and mechanical withdrawal threshold. AMG0347 was also tested against nociceptive behaviors caused by capsaicin. For incisional pain, AMG0347 did not change the withdrawal threshold to mechanical stimulation or the guarding pain score. The withdrawal latency to heat increased from 3 h through 1 day after AMG0347 administration. AMG0347 prevented the decreases in heat withdrawal latency and mechanical withdrawal threshold caused by capsaicin infiltration and prevented the increase in activity caused by intrathecal capsaicin injection. Doses of morphine less than 1 mg/kg inhibited both the guarding and heat hyperalgesia; only the 1-mg/kg does affected mechanical responses. AMG0347 decreased capsaicin-induced heat and mechanical hyperalgesia and blocked central TRPV1 receptors. AMG0347 only decreased heat hyperalgesia after plantar incision even though both peripheral and central TRPV1 receptors were blocked. The smallest doses of morphine affected guarding pain and heat responses.