TY - JOUR
T1 - Role of spinal muscarinic and nicotinic receptors in clonidine-induced nitric oxide release in a rat model of neuropathic pain
AU - Xu, Zemin
AU - Chen, Shao Rui
AU - C. Eisenach, James
AU - Pan, Hui Lin
N1 - Funding Information:
This study was supported by HL-60026 (to H.L. Pan) and GM-35523 (to J.C. Eisenach) from the National Institutes of Health. Dr. Pan currently holds an Independent Scientist Career Award from the National Heart, Lung, and Blood Institute.
PY - 2000/4/14
Y1 - 2000/4/14
N2 - Intrathecal administration of α2 adrenergic agonists, such as clonidine, is capable of alleviating neuropathic pain. Recent studies suggest that spinal nitric oxide (NO) mediates the analgesic effect of intrathecal clonidine. Furthermore, compared to nicotinic receptors, spinal muscarinic receptors play a greater role in the analgesic effect of intrathecal clonidine. In the present study, we tested a hypothesis that clonidine-evoked NO release is dependent primarily on muscarinic receptors in the spinal cord after nerve injury. A rat model of neuropathic pain was induced by ligation of the left L5/L6 spinal nerves. Using an in vitro spinal cord perfusion preparation, the effect of muscarinic and nicotinic receptor antagonists on clonidine-evoked nitrite (a stable product of NO) release was determined. Both muscarinic and nicotinic antagonists dose-dependently attenuated clonidine-elicited nitrite release. In spinal cords from the neuropathic rats, the inhibitory effect of muscarinic receptor antagonists (atropine and scopolamine) on clonidine-elicited nitrite release was more potent than that of nicotinic receptor antagonists (mecamylamine and hexamethonium). However, in spinal cords obtained from sham animals, the inhibitory effect of muscarinic and nicotinic antagonists did not differ significantly. These results indicate that muscarinic, as well as nicotinic, receptors mediate clonidine-induced NO release in the spinal cord. These data also suggest that after nerve injury, the cascade of activation of α2 adrenergic receptors-muscarinic receptors-NO in the spinal cord likely plays a predominant role in the analgesic effect of intrathecal clonidine on neuropathic pain. Copyright (C) 2000 Elsevier Science B.V.
AB - Intrathecal administration of α2 adrenergic agonists, such as clonidine, is capable of alleviating neuropathic pain. Recent studies suggest that spinal nitric oxide (NO) mediates the analgesic effect of intrathecal clonidine. Furthermore, compared to nicotinic receptors, spinal muscarinic receptors play a greater role in the analgesic effect of intrathecal clonidine. In the present study, we tested a hypothesis that clonidine-evoked NO release is dependent primarily on muscarinic receptors in the spinal cord after nerve injury. A rat model of neuropathic pain was induced by ligation of the left L5/L6 spinal nerves. Using an in vitro spinal cord perfusion preparation, the effect of muscarinic and nicotinic receptor antagonists on clonidine-evoked nitrite (a stable product of NO) release was determined. Both muscarinic and nicotinic antagonists dose-dependently attenuated clonidine-elicited nitrite release. In spinal cords from the neuropathic rats, the inhibitory effect of muscarinic receptor antagonists (atropine and scopolamine) on clonidine-elicited nitrite release was more potent than that of nicotinic receptor antagonists (mecamylamine and hexamethonium). However, in spinal cords obtained from sham animals, the inhibitory effect of muscarinic and nicotinic antagonists did not differ significantly. These results indicate that muscarinic, as well as nicotinic, receptors mediate clonidine-induced NO release in the spinal cord. These data also suggest that after nerve injury, the cascade of activation of α2 adrenergic receptors-muscarinic receptors-NO in the spinal cord likely plays a predominant role in the analgesic effect of intrathecal clonidine on neuropathic pain. Copyright (C) 2000 Elsevier Science B.V.
KW - Acetylcholine
KW - Cholinergic receptor
KW - Neuropathic pain
KW - Nitric oxide synthase
KW - α Adrenergic receptor
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U2 - 10.1016/S0006-8993(00)02051-5
DO - 10.1016/S0006-8993(00)02051-5
M3 - Article
C2 - 10760500
AN - SCOPUS:0034646956
SN - 0006-8993
VL - 861
SP - 390
EP - 398
JO - Brain Research
JF - Brain Research
IS - 2
ER -