Abstract
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.
Keywords
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Article info
Publication history
Accepted:
December 9,
1998
Received in revised form:
July 2,
1998
Received:
December 3,
1997
Identification
Copyright
© 1999 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.