2. Academic Validation
  3. Transient receptor potential canonical 5 mediates inflammatory mechanical and spontaneous pain in mice

Transient receptor potential canonical 5 mediates inflammatory mechanical and spontaneous pain in mice

  • Sci Transl Med. 2021 May 26;13(595):eabd7702. doi: 10.1126/scitranslmed.abd7702.
Katelyn E Sadler 1,  Francie Moehring 1,  Stephanie I Shiers 2,  Lauren J Laskowski 1,  Alexander R Mikesell 1,  Zakary R Plautz 1,  Allison N Brezinski 1,  Christina M Mecca 3,  Gregory Dussor 2,  Theodore J Price 2,  John D McCorvy 1,  Cheryl L Stucky 4
Affiliations

Affiliations

  • 1 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • 2 School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, USA.
  • 3 Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • 4 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA. cstucky@mcw.edu.
PMID: 34039739 DOI: 10.1126/scitranslmed.abd7702
Abstract

Tactile and spontaneous pains are poorly managed symptoms of inflammatory and neuropathic injury. Here, we found that transient receptor potential canonical 5 (TRPC5) is a chief contributor to both of these sensations in multiple rodent pain models. Use of TRPC5 knockout mice and inhibitors revealed that TRPC5 selectively contributes to the mechanical hypersensitivity associated with CFA injection, skin incision, chemotherapy induced peripheral neuropathy, sickle cell disease, and migraine, all of which were characterized by elevated concentrations of lysophosphatidylcholine (LPC). Accordingly, exogenous application of LPC induced TRPC5-dependent behavioral mechanical allodynia, neuronal mechanical hypersensitivity, and spontaneous pain in naïve mice. Lastly, we found that 75% of human sensory neurons express TRPC5, the activity of which is directly modulated by LPC. On the basis of these results, TRPC5 inhibitors might effectively treat spontaneous and tactile pain in conditions characterized by elevated LPC.

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