The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in pro- inflammatory cy tokine induced pain behaviors. Intrathecal injection of tumor necrosis factor-a (TNF-${alpha}$; 100 pg), interleukin-1${eta}$ (IL-1${eta}$ 100 pg) and interferon-${gamma}$ (INF-${gamma}$; 100 pg) showed pain behavior. Intrathecal pretreatment with CTX (0.05, 0.1 and 0.5 mg) attenuated pain behavior induced by TNF-${alpha}$ and INF-${gamma}$ administered intrathecally. But intrathecal pretreatment with CTX (0.05, 0.1 and 0.5${mu}g$) did not attenuate pain behavior induced by IL-1${eta}$. On the other hand, intrathecal pretreatment with PTX further increased the pain behavior induced by TNF-${alpha}$ and IL-1${eta}$ administered intrathecally, especially at the dose of 0.5 ${mu}g$. But intrathecal pretreatment with PTX did not affect pain behavior induced by INF-${gamma}$. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play important roles in modulating pain behavior induced by pro-inflammatory cytokines administered spinally. Furthermore, TNF-${alpha}$, IL-1${eta}$ arid INF-${gamma}$ administered spinally appear to produce pain behavior by different mechanisms.