Intrathecal (i.t.) administration of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline enhances pain behaviors in the formalin test. This study examined whether bicuculline also increases the peripheral inflammation induced by formalin. Subcutaneous injection of 0.25 to 5.0% formalin in the plantar surface of one hindpaw of the rat produced a concentration-dependent increase in plasma extravasation as measured by the Evans Blue method. Pretreatment with 0.3 microg i.t. bicuculline neither enhanced nor suppressed formalin-induced plasma extravasation. This dose of bicuculline also did not affect plasma extravasation induced by injection of 3% kaolin/3% carrageenan in the knee of the rat. These data indicate that the enhancement of formalin-induced pain behaviors by i.t. bicuculline is not secondary to enhanced peripheral inflammation, but more likely reflects enhancement of nociceptive transmission in the spinal cord.
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