Modulation of TRPV1 by Protein Kinase A

摘要

The sensation of pain occurs when noxious thermal, mechanical, or chemical stimuli excite nociceptive primary sensory neurons. The sensitivity of these neurons to such stimuli increases with injury, infection, and inflammation, in part due to chemical mediators released from primary sensory nerve terminals and from non-neuronal cells at the site of tissue injury. Sensitization of primary sensory neurons is subserved both by direct interaction of chemical mediators with ion channels and via modulatory effects through G-protein-mediated second-messenger signaling cascades. This chapter summarizes evidence for a role of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) pathway as part of the G_s-mediated signaling cascade in the sensitization of primary sensory neurons. We particularly focus on its modulatory effect on the polymodal transmembrane transducer molecule TRPV1, which was initially discovered as the capsaicin (vanilloid) receptor.