Intrathecal alpha2 adrenoceptor agonist clonidine inhibits mechanical transmission in mouse spinal cord via activation of muscarinic M1 receptors

Neurosci Lett. 2002 Apr 12;322(3):161-4. doi: 10.1016/s0304-3940(02)00073-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists*
  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic alpha-Antagonists / pharmacology
  • Analgesics / pharmacology
  • Animals
  • Clonidine / administration & dosage
  • Clonidine / pharmacology*
  • Hot Temperature
  • Injections, Spinal
  • Male
  • Mechanoreceptors / drug effects*
  • Mice
  • Muscarinic Antagonists / pharmacology
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Physical Stimulation
  • Reaction Time / drug effects
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic / drug effects*
  • Spinal Cord / drug effects*
  • Synaptic Transmission / drug effects*
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Analgesics
  • Muscarinic Antagonists
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic
  • Yohimbine
  • Clonidine