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

Katelyn E Sadler1, Francie Moehring1, Stephanie I Shiers2

  • 1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Science Translational Medicine
|May 27, 2021
PubMed

Insights

Transient receptor potential canonical 5 (TRPC5) channels significantly contribute to tactile and spontaneous pain by responding to lysophosphatidylcholine (LPC). TRPC5 inhibitors show promise for managing pain conditions linked to elevated LPC levels.

Area of Science:

  • Neuroscience
  • Pain Research
  • Molecular Biology

Background:

  • Tactile and spontaneous pain are challenging symptoms of inflammatory and neuropathic injuries.
  • Current management strategies for these pain types are often inadequate.

Purpose of the Study:

  • To investigate the role of transient receptor potential canonical 5 (TRPC5) in tactile and spontaneous pain.
  • To explore the potential of targeting TRPC5 for pain management.

Main Methods:

  • Utilized TRPC5 knockout mice and pharmacological inhibitors in various rodent pain models.
  • Measured behavioral and neuronal responses to pain stimuli.
  • Assessed the impact of lysophosphatidylcholine (LPC) on TRPC5 activity and pain.

Main Results:

  • TRPC5 was identified as a key contributor to mechanical hypersensitivity in models of CFA injection, skin incision, chemotherapy-induced peripheral neuropathy, sickle cell disease, and migraine.
  • Elevated lysophosphatidylcholine (LPC) concentrations were observed in these pain conditions.
  • Exogenous LPC application induced TRPC5-dependent mechanical allodynia, neuronal hypersensitivity, and spontaneous pain.
  • Human sensory neurons express TRPC5, and its activity is modulated by LPC.

Conclusions:

  • TRPC5 plays a critical role in mediating tactile and spontaneous pain, particularly in conditions with elevated LPC.
  • TRPC5 inhibitors represent a potential therapeutic strategy for managing diverse pain states characterized by high LPC levels.

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