GABAB receptors on central terminals of C-afferents mediate intersegmental Aδ-afferent evoked hypoalgesia

The current study tested the hypothesis that repetitive activation of sciatic A delta-afferents evokes a saphenous C-afferent hypoalgesia mediated by pre-synaptic GABA(B) receptors. Tonic activation of sciatic A delta-afferents was produced by cutaneous application of dimethyl sulfoxide (DMSO) followed by repetitive thermal activation of A delta-afferents on the dorsolateral hind paw. The tonic activation of sciatic A delta-afferents produced hypoalgesia in saphenous C-afferents. Intrathecal administration of the GABAB receptor antagonist, saclofen, attenuated saphenous hypoalgesia demonstrating at least partial mediation by central GABA(B) receptors. To determine if this central GABA(B) receptor activation occurs at pre-synaptic primary afferent terminals or postsynaptic spinal cord neurons, the dorsal hind paws of mice were infected with a recombinant herpes simplex virus type 1 (HSV-1) designed to selectively knockdown expression of the GABA(B1a) receptor subunit (PAGB1a) in primary afferents or a control virus encoding the K coli lacZ gene (PZ). Four weeks after infection, GABA(B) receptor immunoreactivity in the superficial dorsal horns ipsilateral to PAGB(1a) application was reduced and hypoalgesia in saphenous C-afferents was attenuated when compared to PZ-infected mice. These findings indicate an intersegmental, sciatic A delta-afferent-evoked hypoalgesic effect on saphenous C-afferent responses that is mediated by pre-synaptic GABA(B) receptors on the terminals of those C-afferents. (c) 2004 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.