No abstract

The GABAergic inhibitory system in the dorsal horn of the spinal cord has been implicated in the modulation of pain, including the control of nociceptive transmission during inflammation. This electrophysiological study examined the effects of the GABAA and GABAB receptor antagonists, bicuculline and CGP35348, on the magnitude and duration of the formalin response. The responses of spinal nociceptive dorsal horn neurones to subcutaneous injection of formalin into the hindpaw in the anaesthetized rat were recorded. Both phases of the formalin response were monitored, and the antagonists were administered either simultaneously with formalin or 50 min after injection of formalin. Bicuculline (50 microg), the GABAA antagonist, administered simultaneously with formalin significantly increased the magnitude of the overall response, especially the second phase, and also abolished the silent interphase period. In addition, 50 min after injection of formalin, bicuculline increased the duration of the second phase in a dose-dependent manner. CGP35348 (250 microg), the GABAB antagonist, administered 50 min after injection of formalin also increased the duration of the second phase significantly, but had no effect on the magnitude of the response or the silent interphase when administered simultaneously with formalin. These results show that GABAA- and GABAB-receptor-mediated inhibitions are involved in controlling the duration of the second phase of the formalin response, and that GABAA-receptor-mediated inhibition also contributes to the manifestation of the silent interphase period and the magnitude of the second phase. Thus, GABA neurones are critical in determining the level and duration of nociceptive information transmitted through the spinal cord during inflammation.