LAUSR

Transforming growth factor‐β1 (TGF‐β1) is an important member of multifunctional growth factor superfamily. It has been implicated in pain signaling, but little is known about the underlying mechanisms. Herein, we report that TGF‐β1 can exert a sustained enhancing effect on the functional activity of acid‐sensing ion channels (ASICs) in rat dorsal root ganglia (DRG) neurons. Pre‐application of TGF‐β1 increased the amplitude of proton‐gated currents in a dose‐dependent manner. Enhancement of ASIC currents lasted for more than 30 min although TGF‐β1 was treated once only. This sustained enhancement by TGF‐β1 could be blocked by extracellular treatment of selective TGF‐β receptor I antagonist SD‐208, and abolished by blockade of intracellular several non‐Smad‐signaling pathways. TGF‐β1 also sustainedly enhanced proton‐evoked spikes in rat DRG neurons. Moreover, peripheral pre‐treatment with TGF‐β1 dose‐dependently exacerbated nociceptive behaviors evoked by intraplantar injection of acetic acid through TGF‐β receptor I in rats. These results suggested that TGF‐β1 potentiated ASIC‐mediated electrophysiological activity and nociceptive behaviors, which revealed a novel mechanism underlying TGF‐β1 implicated in peripheral pain signaling by sensitizing ASICs.