S1PR3 Mediates Itch and Pain via Distinct TRP Channel-Dependent Pathways.

摘要: Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with variety of chronic pain and itch disorders. S1P has been linked to cutaneous pain, but its role in not yet studied. Here, we find that triggers male mice concentration-dependent manner, low levels triggering acute alone high both itch. Ca2+ imaging electrophysiological experiments revealed signals via receptor 3 (S1PR3) TRPA1 subset pruriceptors S1PR3 TRPV1 heat nociceptors. Consistent these findings, S1P-evoked behaviors are selectively lost lacking TRPA1, whereas hypersensitivity TRPV1. We conclude acts different cellular molecular mechanisms trigger pain. Our discovery elucidates the diverse roles plays somatosensation provides insight into how discriminated periphery.SIGNIFICANCE STATEMENT Itch major health problems few effective treatments. show proinflammatory sphingosine receptor, (S1PR3), distinct mechanisms. results provide detailed understanding play somatosensation, highlighting their potential as targets for analgesics antipruritics, new mechanistic underpinnings versus discrimination periphery.