Activin A acutely sensitizes the capsaicin-induced current in the cultured DRG neurons through the activin type I receptor ALK4 and PKC activation. A, Representative current traces from individual DRG neurons challenged by two 50 nm capsaicin (Cap) administrations separated by a 10 min treatment with vehicle, 10 ng/ml activin A, or 10 ng/ml activin plus a test reagent (additional 10 min pretreatment). The reagents tested were 20 μm SB431542 (ALK4 inhibitor), 10 μm PD98059 (MEK inhibitor), 5 μm U0126 (MEK inhibitor), 10 μm LY294002 (PI3K inhibitor), 5 μm H89 (PKA inhibitor), or 1 μm BIM (PKC inhibitor). B, Summary data (mean ± SEM) of normalized capsaicin responses (second peak current/first peak current; note change in scale after axis break) indicate that activin acts to sensitize capsaicin currents in DRG neurons through ALK4 and involves protein kinase C, but not Erk1/2, PI3K, or PKA. Additional data represent tests of activin-induced sensitization with the pseudosubstrate peptide inhibitor of PKC included in the recording pipette solution (2 μm). **p < 0.01 compared with control values. Number of observations are indicated next to each data point.