Open AccessTransient receptor potential canonical 5 mediates inflammatory mechanical and spontaneous pain in mice
Author(s) -
Katelyn E. Sadler,
Francie Moehring,
Stephanie Shiers,
Lauren J. Laskowski,
Alexander R. Mikesell,
Zakary R. Plautz,
Allison N. Brezinski,
Christina M. Mecca,
Gregory Dussor,
Theodore J. Price,
John D. McCorvy,
Cheryl L. Stucky
Publication year - 2021
Publication title -
science translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.819
H-Index - 216
eISSN - 1946-6242
pISSN - 1946-6234
DOI - 10.1126/scitranslmed.abd7702
Subject(s) - transient receptor potential channel , transient (computer programming) , receptor , medicine , inflammation , neuroscience , chemistry , pharmacology , biology , immunology , computer science , operating system
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.