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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-2 Receptor Agonists*
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Adrenergic alpha-Agonists / administration & dosage
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Adrenergic alpha-Agonists / pharmacology*
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Adrenergic alpha-Antagonists / pharmacology
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Analgesics / pharmacology
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Animals
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Clonidine / administration & dosage
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Clonidine / pharmacology*
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Hot Temperature
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Injections, Spinal
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Male
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Mechanoreceptors / drug effects*
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Mice
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Muscarinic Antagonists / pharmacology
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Pain Measurement / drug effects
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Pain Threshold / drug effects
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Physical Stimulation
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Reaction Time / drug effects
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Receptor, Muscarinic M1
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Receptors, Muscarinic / drug effects*
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Spinal Cord / drug effects*
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Synaptic Transmission / drug effects*
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Yohimbine / pharmacology
Substances
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Adrenergic alpha-2 Receptor Agonists
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Analgesics
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Muscarinic Antagonists
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Receptor, Muscarinic M1
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Receptors, Muscarinic
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Yohimbine
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Clonidine