Low and high doses of midazolam differentially affect hypoalgesia in rats conditioned to a heat stressor.

These experiments examined the effects of a benzodiazepine (midazolam) on rats' sensitivity-reactivity to the heated floor of a hot-plate apparatus. Rats were either previously exposed to the heated floor, or naive to the hot-plate apparatus, while control rats were familiarized with the apparatus in the absence of pain. A low dose (0.63 or 1.25 mg/kg) of midazolam attenuated the conditioned hypoalgesic response resulting from pre-exposure to a heated floor, but did not affect the hypoalgesic response elicited by exposure to a novel hot-plate apparatus nor the "baseline" sensitivity-reactivity among control rats. A high dose (2.5 mg/kg) of midazolam resulted in a naloxone-insensitive increase in both the conditioned and the novelty-induced hypoalgesia, and provoked a small, but naloxone-reversible increase in paw-lick latencies among control rats. The results were taken to mean that exposure to the heated floor results in hypoalgesic responses as a consequence of fear conditioning and the reinstatement of novelty. Midazolam was assumed to attenuate conditioned hypoalgesia by reducing fear but at the high dose to augment the hypoalgesic effects of novelty.