Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0030193 (
pain
)
261,466
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic pain and itch disorders. S1P signaling has been linked to cutaneous
pain
, but its role in itch has not yet been studied. Here, we find that S1P triggers itch and
pain
in male mice in a concentration-dependent manner, with low levels triggering acute itch alone and high levels triggering both
pain
and itch. Ca
2+
imaging and electrophysiological experiments revealed that S1P signals via
S1P receptor 3
(
S1PR3
) and TRPA1 in a subset of pruriceptors and via
S1PR3
and TRPV1 in a subset of heat nociceptors. Consistent with these findings, S1P-evoked itch behaviors are selectively lost in mice lacking TRPA1, whereas S1P-evoked acute pain and heat hypersensitivity are selectively lost in mice lacking TRPV1. We conclude that S1P acts via different cellular and molecular mechanisms to trigger itch and
pain
. Our discovery elucidates the diverse roles that S1P signaling plays in somatosensation and provides insight into how itch and
pain
are discriminated in the periphery.
SIGNIFICANCE STATEMENT
Itch and
pain
are major health problems with few effective treatments. Here, we show that the proinflammatory lipid sphingosine 1-phosphate (S1P) and its receptor,
S1P receptor 3
(
S1PR3
), trigger itch and
pain
behaviors via distinct molecular and cellular mechanisms. Our results provide a detailed understanding of the roles that S1P and
S1PR3
play in somatosensation, highlighting their potential as targets for analgesics and antipruritics, and provide new insight into the mechanistic underpinnings of itch versus
pain
discrimination in the periphery.
...
PMID:S1PR3 Mediates Itch and Pain via Distinct TRP Channel-Dependent Pathways. 3008 22
