Transient receptor potential ankyrin 1 contributes to somatic pain hypersensitivity in experimental colitis

Sci Rep. 2020 May 25;10(1):8632. doi: 10.1038/s41598-020-65618-5.

Abstract

Pain evoked by visceral inflammation is often 'referred' to the somatic level. Transient receptor potential ankyrin 1 (TRPA1) has been reported to contribute to visceral pain-like behavior in dextran sulfate sodium (DSS)-evoked colitis. However, the role of TRPA1 in somatic component of hypersensitivity due to visceral inflammation is unknown. The present study investigated the role of TRPA1 in colitis-evoked mechanical hypersensitivity at the somatic level. Colitis was induced in mice by adding DSS to drinking water for one week. Control and DSS-treated mice were tested for various parameters of colitis as well as mechanical pain sensitivity in abdominal and facial regions. DSS treatment caused mechanical hypersensitivity in the abdominal and facial skin. Pharmacological blockade or genetic deletion of TRPA1 prevented the colitis-associated mechanical hypersensitivity in the abdominal and facial skin areas although the severity of colitis remained unaltered. DSS treatment increased expression of TRPA1 mRNA in cultured dorsal root ganglion (DRG) neurons, but not trigeminal ganglion neurons, and selectively enhanced currents evoked by the TRPA1 agonist, allyl isothiocyanate, in cultured DRG neurons. Our findings indicate that the TRPA1 channel contributes to colitis-associated mechanical hypersensitivity in somatic tissues, an effect associated with upregulation of TRPA1 expression and responsiveness in DRG nociceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Animals
  • Colitis / chemically induced
  • Colitis / pathology*
  • Dextran Sulfate / toxicity
  • Evoked Potentials / drug effects
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Isothiocyanates / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nociceptive Pain / pathology*
  • Purines / pharmacology
  • Stress, Mechanical
  • TRPA1 Cation Channel / antagonists & inhibitors
  • TRPA1 Cation Channel / genetics
  • TRPA1 Cation Channel / metabolism*
  • Trigeminal Ganglion / cytology
  • Trigeminal Ganglion / metabolism

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Isothiocyanates
  • Purines
  • TRPA1 Cation Channel
  • Dextran Sulfate
  • allyl isothiocyanate