Tonic cholinergic inhibition of spinal mechanical transmission.
The present study examined the role of spinal cholinergic modulation of spinal mechanical and thermal transmission. Intrathecal administration of the cholinergic muscarinic receptor antagonists atropine or scopolamine in awake rats produced a dose-dependent decrease in the nociceptive mechanical withdrawal threshold of the rat tail. Pirenzepine, a selective muscarinic receptor type 1 antagonist, produced a similar effect at greater doses while mecamylamine, a nicotinic receptor antagonist, was without effect. The nociceptive tail flick (TF) reflex evoked by noxious heating was unaffected by the above drugs. Intrathecal administration of the cholinesterase inhibitor physostigmine produced a rapid, reversible and significant increase in the mechanical withdrawal threshold; TF latency was increased slightly but not significantly. Intrathecal administration of morphine, carbachol or clonidine all produced dose-dependent increases in TF latency; morphine and carbachol, but not clonidine, also increased the mechanical withdrawal threshold significantly. Intrathecal pretreatment with atropine reversed carbachol-produced increases in TF latency and the mechanical withdrawal threshold but did not affect increases in TF latency produced by intrathecal morphine or clonidine. The morphine-produced increase in the mechanical withdrawal threshold, however, was shifted rightward in a parallel fashion by intrathecal pretreatment with atropine. Intrathecal pretreatment with yohimbine did not affect the inhibitory effect of carbachol on either TF latency or the mechanical withdrawal threshold. These results suggest that a tonic, endogenous cholinergic muscarinic influence in the spinal cord, independent of spinal adrenergic mechanisms, modulates spinal mechanical transmission.
Zhuo
M
M
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, IA 52242 U.S.A.
Gebhart
G F
GF
D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology; D018680:Cholinergic Antagonists; D004347:Drug Interactions; D004723:Endorphins / Q000502:physiology; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology*; D010812:Physical Stimulation; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013623:Tail / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D015306:Biogenic Monoamines; D018680:Cholinergic Antagonists; D004723:Endorphins; D010276:Parasympatholytics; D011941:Receptors, Adrenergic; D015016:Yohimbine; D009270:Naloxone; D009020:Morphine; D011224:Prazosin