Intrathecal alpha2 adrenoceptor agonist clonidine inhibits mechanical transmission in mouse spinal cord via activation of muscarinic M1 receptors.
We examined the role of the spinal muscarinic receptor subtype in the anti-nociceptive effect of intrathecal (i.t.) alpha2 adrenoceptor agonist clonidine in mice. I.t. injection of the muscarinic receptor antagonist atropine completely inhibited i.t. clonidine-induced increase in the mechanical threshold, but did not affect the increase in tail-flick latency induced by i.t. clonidine. The clonidine-induced increase in mechanical threshold was inhibited by i.t. injection of the M1 receptor antagonist pirenzepine in a dose-dependent manner, and by the M3 receptor antagonist 4-DAMP, but not by the M2 receptor antagonist methoctramine. The potency of pirenzepine was greater than that of 4-DAMP. These results suggest that the clonidine-induced increase in mechanical threshold is mediated via the activation of M1 receptors in the spinal cord.
Honda
Kenji
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180, Japan. khonda@fukuoka-u.ac.jp
Koga
Kohei
K
Moriyama
Tomoko
T
Koguchi
Masako
M
Takano
Yukio
Y
Kamiya
Hiro-o
HO
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D011930:Reaction Time / Q000187:drug effects; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D015016:Yohimbine; D003000:Clonidine