Abstract
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 30min 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.
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