S1PR3 mediates itch and pain via distinct TRP channel-dependent pathways

Abstract

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A nervous S1P of the lung: activation of airway nerves by sphingosine‐1‐phosphate

“…The intracellular signalling that links S1PR3 activation with airway nociceptor depolarization is presently unknown, although Patil et al (2019) have ruled out signalling via the nociceptive transient receptor potential channels vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1). This observation is inconsistent with some somatosensory nociceptor studies (Hill et al 2018), and these differences in signalling mimics reports of S1P receptors coupling with different Gα proteins in different innate immunity cell types. S1P activates both proinflammatory and anti-inflammatory pathways, and the balance between these pathways depends on the S1P concentration and the receptors and cell types involved.…”

“…This observation is inconsistent with some somatosensory nociceptor studies (Hill et al . ), and these differences in signalling mimics reports of S1P receptors coupling with different Gα proteins in different innate immunity cell types.…”

“…; Hill et al . ). The intracellular signalling that links S1PR3 activation with airway nociceptor depolarization is presently unknown, although Patil et al .…”

“…It is likely that vagal nociceptors innervating other visceral organs will also be activated by S1P. S1P has also been shown to activate somatosensory nociceptors in the skin via S1PR3 (Camprubi-Robles et al 2013;Hill et al 2018). The intracellular signalling that links S1PR3 activation with airway nociceptor depolarization is presently unknown, although Patil et al (2019) have ruled out signalling via the nociceptive transient receptor potential channels vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1).…”

Genomewide Meta‐Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent‐Induced Sensory Peripheral Neuropathy

“…Interestingly, activation of S1PR 3 may also be involved in sensory neurite retraction, nociceptor excitability, and pain-like symptoms. 29,36,40 FTY720 has also been shown to bind to S1PR 3 and other receptors, 38 although its functional activity is largely attributed to S1PR 1 binding. Although expression of both S1PR 1 and S1PR 3 are known in primary DRG 41 and iP-SC-derived SNs used in these studies ( Figure S25), the exact role of these receptors in sensory PN is not yet clear.…”