INTRATHECAL GAMMA-AMINOBUTYRIC ACID(B) (GABA(B)) RECEPTOR ANTAGONIST CGP-35348 INDUCES HYPERSENSITIVITY TO MECHANICAL STIMULI IN THE RAT

Intrathecal (i.t.) administration of the gamma-aminobutyric acid(B) (GABA(B)) receptor antagonist CGP 35348 in the rat resulted in a dose-dependent pain-like response (vocalization) to innocuous mechanical stimulation(tactile stimuli and touch/pressure). The effect was maximally evoked by stimulation applied to a dermatome corresponding to the spinal levels of the i.t. injections. The paw withdrawal threshold to pressure was also moderately decreased after i.t. CGP 35348. In contrast, i.t. CGP 35348 had no effect on the hot plate test. It is suggested that the input of low threshold afferents innervating mechanoceptors is tonically inhibited by the GABA system through B-type receptors, and blockade of this system results in mechanical hypersensitivity that is similar to mechanical allodynia (painful response to innocuous stimulation) observed in humans.