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

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...

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Published in:Science translational medicine 2021-05, Vol.13 (595), p.1
Main Authors: Sadler, Katelyn E, Moehring, Francie, Shiers, Stephanie I, Laskowski, Lauren J, Mikesell, Alexander R, Plautz, Zakary R, Brezinski, Allison N, Mecca, Christina M, Dussor, Gregory, Price, Theodore J, McCorvy, John D, Stucky, Cheryl L
Format: Article
Language:English
Subjects:
Animal models
Animals
Chemotherapy
Headache
Hyperalgesia
Hypersensitivity
Inflammation
Lysophosphatidylcholine
Mechanical properties
Mice
Mice, Knockout
Migraine
Pain
Pain perception
Peripheral neuropathy
Sensory neurons
Sensory Receptor Cells
Sickle cell disease
Touch
Transient receptor potential proteins
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Summary: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 , 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.
ISSN:1946-6234
1946-6242
1946-3242
DOI:10.1126/scitranslmed.abd7702