Korean J Anesthesiol.  1998 Jun;34(6):1104-1112. 10.4097/kjae.1998.34.6.1104.

The Effect of Selective Muscarinic Receptor Antagonists on Antiallodynic Action in a Rat Model of Neuropathic Pain

Affiliations
  • 1Department of Anesthesiology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea.

Abstract

BACKGROUND: Peripheral nerve injury may produce a syndrome consisting of spontaneous pain, allodynia and hyperpathia. In previous study, we examined the antiallodynic action produced by intrathecal (i.t.) cholinesterase inhibitors (ChEi) in a neuropathic pain rat model and the reversal of antiallodynic state by i.t. atropine, muscarinic antagonist, but not by nicotinic antagonist mecamylamine. The purpose of this study was to determine the selective antagonistic action of four subtypes of muscarinic receptor on antiallodynic state by i.t. ChEi in a rat model of neuropathic pain.
METHODS
Sprague Dawley rats were prepared with tight ligation of left L5/L6 spinal nerves with 6-0 black silk and chronic lumbar intrathecal catheters. After obtaining the baseline hindpaw withdrawal scores, edrophonium (100 microgram) or neostigmine (10 microgram) was administered intrathecally. Tactile allodynia was measured using von Frey filaments and allodynic threshold was calculated by the up-down method. Allodynic changes were tested at 15, 30, 45, 60, 90, 120 and 180 minutes. To examine the reversal of antiallodynia and to compare the antagonizing action of antiallodynic state produced by i.t. administration of ChEi, non-selective muscarinic receptor antagonists atropine (10 microgram), M1 antagonist pirenzepine (3 microgram), M2 antagonist methoctramine (3 microgram), M3 antagonist 4-DAMP (3 microgram) and M4 antagonist tropicamide (3 microgram) were injected intrathecally respectively 5 minutes prior to the injection of edrophonium or neostigmine.
RESULTS
Antiallodynia produced by i.t. edrophonium was reversed by pretreatment with i.t. methoctramine, 4-DAMP, tropicamide and pirenzepine (P<0.05). On the contrary, antiallodynic state made by i.t. neostigmine was not antagonized by methoctramine, 4-DAMP and tropicamide. M1 antagonist pirenzepine had a moderate, statistically significant (P<0.05) effect on reversal of increased allodynic threshold while atropine showed a complete antagonism.
CONCLUSION
These experiments suggest that antialllodynic action of cholinesterase inhibitors is likely due to mediation of spinal muscarinic system and M1 receptor subtype is more likely involved in this mechanism.

Keyword

Antagonist: atropine; pirenzepine; methoctramine; 4-DAMP; tropicamide; Cholinesterase inhibitor: edrophonium; neostigmine; Pain, neuropathic: allodynia; Receptor: muscarinic

MeSH Terms

Animals
Atropine
Catheters
Cholinesterase Inhibitors
Edrophonium
Hyperalgesia
Ligation
Mecamylamine
Models, Animal*
Negotiating
Neostigmine
Neuralgia*
Peripheral Nerve Injuries
Pirenzepine
Rats*
Rats, Sprague-Dawley
Receptors, Muscarinic*
Silk
Spinal Nerves
Tropicamide
Atropine
Cholinesterase Inhibitors
Edrophonium
Mecamylamine
Neostigmine
Pirenzepine
Receptors, Muscarinic
Silk
Tropicamide
Full Text Links
  • KJAE
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error