Systemic administration of opiates or direct injection of opioid peptides into the periaqueductal gray (PAG) produces a profound antinociception which is thought to be associated with inhibition of neuronal activity in the PAG. This inhibitory effect has been postulated to result from opiate inhibition of GABAergic neurons in the PAG. Whether this opioid- GABAergic system is affected in acute pain state has not been investigated. The present study was thus designed to determine the effects of unilateral peripheral inflammation on ventrocaudal PAG γ-aminobutyric acid (GABA) release in the rat using in vivo microdialysis and subsequent high pressure liquid chromatography (HPLC) analysis. Microdialysis was chosen to perform direct and dynamic studies of amino acid concentrations in the PAG in control rats and in animals subjected to acute and prolonged inflammation caused by injection of 120 μl of Complete Freund's Adjuvant (CFA) into the hind paw. GABA release was significantly decreased in the CFA treated groups both 24 h as well as 7 days post-treatment. GABA release decreased to approximately one-fourth 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 dialysis. Systemic injection of naloxone (5 mg/kg i.p.) caused selective and significant block in the decrease of veratridine-induced release of GABA in the 24 h CFA-treated rats. Taken together with data from our previous studies, these results suggest that the decrease in veratridine-induced GABA release in this study may be due to an increase opiate inhibition of GABA resulting from the induction of acute or prolonged elevation of nociceptive input.
Bibliographical noteFunding Information:
The authors thank Marry Mullet, Lorraine Wellman and Joan Hautman for their excellent technical assistance. This work was supported by NIH grants DA 06687, DE 06682, and NS 28016.
- Central gray
- Excitatory amino acids