Complex changes of GABAA and GABAB receptor binding in the spinal cord dorsal horn following peripheral inflammation or neurectomy

Abstract

Chronic peripheral inflammation or peripheral neurectomy cause changes in GABA levels and GABA immunoreactivity in the spinal cord dorsal horn. The present study aimed to investigate if such changes are accompanied by alterations in GABA receptor binding. Neurectomy of the sciatic nerve caused an ipsilateral down-regulation of GABAB receptor binding in lamina II of the spinal cord 2-4 weeks after the nerve injury. Since approximately 50% of GABAB receptor binding in that region is located on primary afferent endings, degenerative changes of such endings caused by the nerve lesion can explain the observed reduction. In contrast, GABAA binding was substantially enhanced following neurectomy, which may be due to an up-regulation of the receptors issued by the concomitant decrease of endogenous GABA. In rats bearing unilateral chronic peripheral inflammation induced by intraarticular injection of complete Freund's adjuvant we found a reduction of GABAB binding in the superficial dorsal horn. This effect, which was maximal at 3-4 weeks after adjuvant injection, was attributed to an enhanced release of GABA by spinal interneurons. GABAA receptor binding was not changed in this experimental model. Together, these results suggest that the two receptor types may be located at different loci and are differently affected by variations in sensory input.