Role of spinal gamma-aminobutyric acidA receptors in formalin-induced nociception in the rat.

Abstract

This study investigated the role of gamma-aminobutyric acid (GABA) and GABA(A) receptors in the spinal cord in the expression of pain behaviors evoked by injection of formalin in concentrations ranging from 0.25 to 2.5% in the hindpaw of the rat. Two approaches were used. The first approach compared the effect of drug treatment to saline at each concentration of formalin. The second approach examined the effect of drug treatment on the concentration-response functions of formalin, i.e., its EC50. Intrathecal (i.t.) pretreatment with 0.03 to 0.3 microg of bicuculline, a GABA(A) receptor antagonist, dose-dependently increased the number of flinches and weighted pain scores in the interphase and phase 2, but did not alter responses in phase 1. In the interphase, the EC50 values of formalin for number of flinches or weighted pain score in bicuculline-pretreated rats were decreased to one-third or one-fourth, respectively, of their values in saline-pretreated rats. In phase 2, the EC50 values of formalin for number of flinches or weighted pain score in bicuculline-pretreated rats were similarly decreased to one-half of their value in saline-pretreated rats. These results suggest that formalin was a significantly more noxious stimulus in the presence of bicuculline. Pretreatment with the GABA(A) receptor agonists, muscimol (0.3 microg) or isoguvacine (10 or 30 microg i.t.), significantly decreased the number of flinches in phase 1 and phase 2, but produced only a marginal decrease in the weighted pain score at the highest doses. These findings suggest that there is little tonic activation of GABA(A) receptors by GABA in the spinal cord before or immediately after the injection of formalin. However, approximately 10 min after the induction of injury by formalin, there is a release of GABA and activation of GABA(A) receptors in the spinal cord that 1) contributes to the period of quiescence between phase 1 and phase 2 and 2) coincidentally diminishes the magnitude of pain behaviors in phase 2, possibly by limiting the development of central sensitization in the spinal cord.

• Authors: M Kaneko, D L Hammond
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 282 Issue 2 Pg. 928-38 (Aug 1997) ISSN: 0022-3565 [Print] United States
• PMID: 9262360 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• Isonicotinic Acids
• Receptors, GABA-A
• Formaldehyde
• Bicuculline
• isoguvacine

Topics

• Animals
• Bicuculline (administration & dosage, pharmacology)
• Formaldehyde (pharmacology)
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• Injections, Spinal
• Isonicotinic Acids (administration & dosage, pharmacology)
• Male
• Pain (chemically induced, physiopathology)
• Premedication
• Rats
• Rats, Sprague-Dawley
• Receptors, GABA-A (physiology)
• Spinal Cord (physiopathology)