Abstract

The effects of (-)-nicotine and ethylketazocine (EKC) on the latency of a low-intensity thermally evoked tail avoidance response were evaluated at different midline mesencephalic, pontomedullary and medullary sites of conscious intact rats. Guide cannulae were implanted surgically at six anterior-posterior stereotaxic locations (AP, -4.4 to +2.8) and drugs were microinjected (0.5 microliter) at different depths in each region. The analgesic effects of naltrexone and mecamylamine were evaluated at those sites exhibiting sensitivity to the hyperalgesic actions of (-)-nicotine and EKC. Additional experiments evaluated the validity and reproducibility of the low-intensity thermally evoked tail avoidance response and a low intensity hot plate response in detecting hyperalgesia. The chemostimulation studies suggest that there are opioid and nicotinic hyperalgesic processes distributed throughout the dorsal regions of the posterior mesencephalic and pontomedullary brain stem. The relative hyperalgesic potency of (-)-nicotine appears to exhibit a gradient from the dorsal posterior mesencephalic tegmentum to the midmedullary region, whereas only analgesia was produced more rostrally, in the central gray, or caudally within the posterior medulla. Within regions intermediate between the dorsal posterior, mesencephalic tegmentum and posterior medulla, (-)-nicotine produced biphasic dose-response and time action curves. The effects of EKC were similar to those of (-)-nicotine at most sites although (-)-nicotine was 55 times more potent than EKC when administered in the most active hyperalgesic regions.2+ may differ from region to region.