Molecular Switch Triggers Itch

Summary: Researchers have discovered two distinct pathways through which a single molecule can cause both painful and itchy skin.

Source: SfN.

A new study of male mice published in Journal of Neuroscience uncovers two distinct pathways through which a single molecule can cause both itchy and painful skin. The research could inform the development of drugs for a variety of skin diseases.

Diana Bautista and colleagues show that sphingosine 1-phosphate (S1P) — a molecule implicated in skin conditions such as psoriasis as well as other inflammatory diseases including asthma and multiple sclerosis — triggers itch in addition to its known role in pain.

Their work identifies a receptor of this molecule, S1PR3, expressed in sensory neurons is responsible for these sensations.

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A new study of male mice published in JNeurosci uncovers two distinct pathways through which a single molecule can cause both itchy and painful skin. The research could inform the development of drugs for a variety of skin diseases. NeuroscienceNews.com image is credited to Hill et al., JNeurosci (2018).

The findings suggest that blocking this receptor may represent a promising therapeutic approach for managing both pain and itch.

About this neuroscience research article

Source: David Barnstone – SfN
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Hill et al., JNeurosci (2018).
Original Research: Abstract for “S1PR3 mediates itch and pain via distinct TRP channel-dependent pathways” by Rose Z. Hill, Takeshi Morita, Rachel B. Brem and Diana M. Bautista in Journal of Neuroscience. Published August 6 2018.
doi:10.1523/JNEUROSCI.1266-18.2018

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]SfN”Molecular Switch Triggers Itch.” NeuroscienceNews. NeuroscienceNews, 6 August 2018.
<https://neurosciencenews.com/itch-molecular-switch-9663/>.[/cbtab][cbtab title=”APA”]SfN(2018, August 6). Molecular Switch Triggers Itch. NeuroscienceNews. Retrieved August 6, 2018 from https://neurosciencenews.com/itch-molecular-switch-9663/[/cbtab][cbtab title=”Chicago”]SfN”Molecular Switch Triggers Itch.” https://neurosciencenews.com/itch-molecular-switch-9663/ (accessed August 6, 2018).[/cbtab][/cbtabs]


Abstract

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

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. Calcium imaging and electrophysiological experiments revealed that S1P signals via S1PR3 and TRPA1 in a subset of pruriceptors, and via S1PR3 and TRPV1 in a subset of heat nociceptors. In line 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 pro-inflammatory lipid S1P and its receptor 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.

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