Impairment of spinal GABAergic inhibition is demonstrated to contribute to pathologic
chronic pain states. We investigated spinal and peripheral GABAergic regulation of incisional
pain in rats. We found that intrathecal but not peripheral administration of
muscimol (
GABA-A receptor agonist) and
baclofen (
GABA-B receptor agonist) reduced mechanical and
thermal hyperalgesia after plantar incision in rats. Nonevoked
pain behavior after incision was unaffected by these agonists. Similarly, nociception in unincised rats was not reduced by the same dose of agonists. Thus,
GABA-A and
GABA-B receptors are involved in mediating incision-induced
hyperalgesia (but not nonevoked
pain). Intrathecal and systemic application of
L-838,417, a subtype-selective
benzodiazepine site agonist (α2, α3, α5), reduced mechanical and heat
hyperalgesia after incision, indicating a role of these subunits in mediating incision-induced
hyperalgesia. Interestingly, the effects of all agonists were more intense and prolonged on the day after surgery than on the day of incision. Similarly, spinally administered
GABA-A and
GABA-B antagonists increased
pain behavior, again with a greater effect 1 day after incision. One possible explanation for this finding might be that an incision modulates
GABA-mediated inhibition 1 day after incision. However, expression of
GABA-A receptor subunits α2 and α3 and
GABA-B receptor subunits within the dorsal horn of the spinal cord were unchanged after incision, indicating that receptor expression cannot explain a possible modulation of GABAergic inhibition after incision. Thus, other mechanisms need to be considered. In conclusion,
GABA-A and
GABA-B receptors are promising targets for postoperative, incisional
pain in humans.