INCREASED SENSITIVITY TO THE ANTINOCICEPTIVE ACTIVITY OF (+ -)-BACLOFEN IN AN ANIMAL-MODEL OF CHRONIC NEUROPATHIC, BUT NOT CHRONIC INFLAMMATORY HYPERALGESIA/

Modulation of sensory afferent inputs to the spinal cord by GABA appea rs to be an important physiological mechanism and may provide an antin ociceptive control system. In the present study we have evaluated the antinociceptive activity of the GABA(B) receptor agonist, (+)-baclofen , in rats with unilateral chronic inflammatory or neuropathic hyperalg esia. (+)-Baclofen was antinociceptive in untreated control animals an d both animal models. In the neuropathic model the sensitivity to (+)- baclofen was significantly increased by 3-fold in the ipsilateral limb . By contrast, in animals with chronic inflammation no difference in s ensitivity between ipsilateral and contralateral limbs to (+)-baclofen was observed. Receptor autoradiographic analysis in spinal cord secti ons revealed no increase in the density of GABA(B) receptor binding si tes and no change in receptor affinity in the neuropathic model.