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 subjective experience of pain. Both rapid-eye-movement (REM) sleep and nociception are modulated by cholinergic neurotransmission, and this study tested the hypothesis that antinociceptive behavior can be evoked cholinergically from medial pontine reticular formation (mPRF) regions known to regulate REM sleep. The foregoing hypothesis was investigated by quantifying the effect of mPRF drug administration on tail flick latency (TFL) of cat during polygraphically defined sleep/wake states. The mPRF was microinjected with 0.25 ml saline, carbachol (4.0 microg), neostigmine (6.7 microg), or morphine sulfate (14.7 microg), and TFL measures were obtained in response to radiant heat. During wakefulness TFL (% increase) 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 evoked by tail stimulation before and after mPRF microinjections of carbachol. The results show for the first time that mPRF administration of cholinomimetics significantly increased TFL. During NREM sleep and REM sleep, TFL was significantly increased compared to waking TFL (110% and 321%, respectively). The finding of sleep-dependent alterations in TFL demonstrates that mPRF regions known to regulate REM sleep can modulate supraspinal cholinergic antinociceptive behavior.
Kshatri
A M
AM
Department of Anesthesia, The Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Baghdoyan
H A
HA
Lydic
R
R
D000704:Analysis of Variance; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002415:Cats; D018678:Cholinergic Agents / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009388:Neostigmine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D017286:Polysomnography; D011149:Pons / Q000187:drug effects*; D012154:Reticular Formation / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
D018678:Cholinergic Agents; D009294:Narcotics; D009388:Neostigmine; D009020:Morphine; D002217:Carbachol