RESULTS: In order to elucidate the functional relevance of
GABA(B) receptors expressed in peripheral nociceptive neurons in
pain modulation we generated and analyzed conditional mouse mutants lacking functional
GABA(B1) subunit specifically in nociceptors, preserving expression in the spinal cord and brain (SNS-
GABA(B1)-/- mice). Lack of the
GABA(B1) subunit precludes the assembly of functional
GABA(B) receptor. We analyzed SNS-
GABA(B1)-/- mice and their control littermates in several models of acute and
neuropathic pain. Electrophysiological studies on peripheral afferents revealed higher firing frequencies in SNS-
GABA(B1)-/- mice compared to corresponding control littermates. However no differences were seen in basal nociceptive sensitivity between these groups. The development of neuropathic and chronic inflammatory
pain was similar across the two genotypes. The duration of nocifensive responses evoked by intraplantar
formalin injection was prolonged in the SNS-GABAB(1)-/- animals as compared to their control littermates. Pharmacological experiments revealed that systemic
baclofen-induced inhibition of
formalin-induced nociceptive behaviors was not dependent upon
GABA(B1) expression in nociceptors.
CONCLUSION: This study addressed contribution of
GABA(B) receptors expressed on primary afferent nociceptive fibers to the modulation of
pain. We observed that neither the development of acute and
chronic pain nor the
analgesic effects of a systematically-delivered
GABA(B) agonist was significantly changed upon a specific deletion of
GABA(B) receptors from peripheral nociceptive neurons in vivo. This
lets us conclude that
GABA(B) receptors in the peripheral nervous system play a less important role than those in the central nervous system in the regulation of
pain.