Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals

Anesthesiology. 2009 Jul;111(1):147-54. doi: 10.1097/ALN.0b013e3181a1642b.


Background: The TRPA1 ion channel modulates excitability of nociceptors, and it may be activated by compounds resulting from oxidative insults. Diabetes mellitus produces oxidative stress and sensory neuropathy. The authors tested the hypothesis that diabetes-induced endogenous compounds acting on the TRPA1 ion channel contribute to development and maintenance of mechanical hypersensitivity.

Methods: Diabetes mellitus was induced by streptozotocin. Mechanical hypersensitivity was assessed by the monofilament and paw pressure tests. Chembridge-5861528 (CHEM; a TRPA1 channel antagonist, a derivative of HC-030031) or vehicle was administered acutely or twice daily for 10 days in diabetic animals. For comparison, effects of CHEM were assessed in a group of healthy control animals.

Results: Acute administration of CHEM attenuated mechanically induced withdrawal responses in diabetic and control groups. The maximal effect (over 50% elevation of the paw pressure threshold) by acute administration of CHEM was obtained in 30 min. The lowest dose producing a significant attenuation was 10 mg/kg in the diabetic group and 30 mg/kg in the healthy controls. Chronic administration of CHEM (30 mg/kg twice daily) for a week in the diabetic group attenuated development of mechanical hypersensitivity.

Conclusions: Reduction of pain-related behavior by a lower dose of the TRPA1 channel antagonist in the diabetic than in the control group suggests that endogenous compounds resulting from diabetes mellitus and acting on the TRPA1 channel contribute to diabetic hypersensitivity. Prolonged antihypersensitivity effect after chronic treatment suggests that daily administration of a TRPA1 channel antagonist may prevent development of diabetic hypersensitivity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankyrins
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use*
  • Calcium Channels / physiology*
  • Cell Line
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Pain Measurement / drug effects*
  • Pain Measurement / methods
  • Physical Stimulation / adverse effects
  • Rats
  • Rats, Wistar
  • TRPA1 Cation Channel
  • TRPC Cation Channels


  • Ankyrins
  • Calcium Channel Blockers
  • Calcium Channels
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • Trpa1 protein, rat