CHOLINOMIMETICS, BUT NOT MORPHINE, INCREASE ANTINOCICEPTIVE BEHAVIOR FROM PONTINE RETICULAR REGIONS REGULATING RAPID-EYE-MOVEMENT SLEEP

Sleep disruption is a significant problem associated with the subjecti ve experience of pain. Both rapid-eye-movement (REM) sleep and nocicep tion are modulated by cholinergic neurotransmission, and this study te sted the hypothesis that antinociceptive behavior can be evoked cholin ergically from medial pontine reticular formation (mPRF) regions known to regulate REM sleep. The foregoing hypothesis was investigated by q uantifying the effect of mPRF drug administration on tail flick latenc y (TFL) of cat during polygraphically defined sleep/wake states. The m PRF was microinjected with 0.25 ml saline, carbachol (4.0 mu g), neost igmine (6.7 mu g), or morphine sulfate (14.7 mu g), and TFL measures w ere obtained in response to radiant heat. During wakefulness TFL (% in crease) was not increased by morphine or saline, but was significantly increased by mPRF administration of carbachol (42.4%) and neostigmine (35.2%). Cortical somatosensory potentials (SSEPs) were reliably evok ed by tail stimulation before and after mPRF microinjections of carbac hol. The results show for the first time that mPRF administration of c holinomimetics significantly increased TFL. During NREM sleep and REM sleep, TFL was significantly increased compared to waking TFL (110% an d 321%, respectively). The finding of sleep-dependent alterations in T FL demonstrates that mPRF regions known to regulate REM sleep can modu late supraspinal cholinergic antinociceptive behavior.