The effect of suramin, an inhibitor of G protein regulated signalling, was studied on the membrane currents induced by noxious heat and by capsaicin in cultured dorsal root ganglia neurones isolated from neonatal rats. Whole-cell responses induced by a heat ramp (24-52 degreesC) were little affected by suramin. The noxious heat-activated currents were synergistically facilitated in the presence of 0.3 muM capsaicin 13.2-fold and 6.3-fold at 40 degreesC and 50 degreesC, respectively. In 65% of neurones, the capsaicin-induced facilitation was inhibited by 10 muM suramin to 35 +/- 6 % and 53 +/- 6 % of control at 40 degreesC and 50 degreesC (S.E.M., n=15). Suramin 30 muM caused a significant increase in the membrane current produced by a nearly maximal dose (1 muM) of capsaicin over the whole recorded temperature range (2.4-fold at 25 degreesC and 1.2-fold at 48 degreesC). The results demonstrate that suramin differentially affects the interaction between capsaicin and noxious heat in DRG neurones and thus suggest that distinct transduction pathways may participate in vanilloid receptor activation mechanisms.