J Korean Med Sci.  2001 Aug;16(4):498-504. 10.3346/jkms.2001.16.4.498.

Synergistic Effects Between Intrathecal Clonidine and Neostigmine in the Formalin Test

• Yoon MH
• Yoo KY
• Jeong CY

• KMID: 648310
• DOI: http://doi.org/10.3346/jkms.2001.16.4.498

Abstract

Spinal alpha-2 adrenoceptors and cholinergic receptors are involved in the regulation of acute nociception and the facilitated processing. The aim of this study was to examine the pharmacological effect of an intrathecal alpha-2 agonist and a cholinesterase inhibitor on the facilitated pain model induced by formalin injection and to determine the nature of drug interaction using an isobolographic analysis. Both intrathecal clonidine and neostigmine dose-dependently suppressed the flinching during phase 1 and phase 2. Intrathecal pretreatment with atropine reversed the antinociceptive effects of clonidine and neostigmine in both phases. Pretreatment with intrathecal yohimbine attenuated the effect of clonidine. The antinociception of clonidine and neostigmine was not reversed by mecamylamine. Isobolographic analysis showed that intrathecal clonidine and neostigmine acted synergistically in both phase 1 and 2. Intrathecal pretreatment with atropine and yohimbine antagonized the effect of the mixture of clonidine and neostigmine in both phases, but no antagonism was observed with mecamylamine pretreatment. These data indicate that spinal clonidine and neostigmine are effective to counteract the facilitated state evoked formalin stimulus, and these two drugs interact in a synergistic fashion. In addition, the analgesic action of intrathecal clonidine is mediated by spinal muscarinic receptors as well as alpha-2 adrenoceptors.

Keyword

Analgesics; Antinociception; Intrathecal; Clonidine; Neostigmine; Drug Interactions

MeSH Terms

Adrenergic alpha-Agonists/*pharmacology
Analgesics, Non-Narcotic/*pharmacology
Animal
Cholinesterase Inhibitors/*pharmacology
Clonidine/administration & dosage/*pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Formaldehyde
Injections, Spinal
Male
Neostigmine/administration & dosage/*pharmacology
Pain/drug therapy
Rats
Rats, Sprague-Dawley