Peripheral inflammation is associated with decreased veratridine-induced release of GABA in the rat ventrocaudal periaqueductal gray: microdialysis study

Systemic administration of opiates or direct injection of opioid peptides i nto the periaqueductal gray (PAG) produces a profound antinociception which is thought to be associated with inhibition of neuronal activity in the PA G. This inhibitory effect has been postulated to result from opiate inhibit ion of GABAergic neurons in the PAG. Whether this opioid-GABAergic system i s affected in acute pain state has not been investigated. The present study was thus designed to determine the effects of unilateral peripheral inflam mation on ventrocaudal PAG gamma-aminobutyric acid (GABA) release in the ra t using in vivo microdialysis and subsequent high pressure liquid chromatog raphy (HPLC) analysis. Microdialysis was chosen to perform direct and dynam ic studies of amino acid concentrations in the PAG in control rats and in a nimals subjected to acute and prolonged inflammation caused by injection of 120 mu l of Complete Freund's Adjuvant (CFA) into the hind paw. GABA relea se was significantly decreased in the CFA treated groups both 24 h as well as 7 days post-treatment. GABA release decreased to approximately one-fourt h that of the 24 h mineral oil control group. Likewise, veratridine-induced release of GABA was decreased in rats treated with CFA 7 days prior to dia lysis. Systemic injection of naloxone (5 mg/kg i.p.) caused selective and s ignificant block in the decrease of veratridine-induced release of GABA in the 24 h CFA-treated rats. Taken together with data from our previous studi es, these results suggest that the decrease in veratridine-induced GABA rel ease in this study may be due to an increase opiate inhibition of GABA resu lting from the induction of acute or prolonged elevation of nociceptive inp ut. (C) 1999 Elsevier Science BN; All rights reserved.