Mechanical antihypersensitivity effect induced by repeated spinal administrations of a TRPA1 antagonist or a gap junction decoupler in peripheral neuropathy

Hong Wei, Hai Yun Wu, Zuyue Chen, Ai Niu Ma, Xiao Fang Mao, Teng Fei Li, Xin Yan Li, Yong Xiang Wang*, Antti Pertovaara

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

8 Citations (Scopus)

Abstract

Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by D-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH). Experiments were performed in rats with spared nerve injury (SNI) and chronic intrathecal catheter. Drugs were administered twice daily for the first seven injury days or only once seven days after injury. Mechanical hypersensitivity was assessed with monofilaments. Acute and prolonged treatment with Chembridge-5861528 (a TRPA1 antagonist), carbenoxolone (an inhibitor of activated astrocytes), or gabapentin (a comparison drug) attenuated tactile allodynia-like responses evoked by low (2 g) stimulus. However, antihypersensitivity effect of these compounds was short of significance at a high (15 g) stimulus intensity. No preemptive effects were observed. In healthy controls, carbenoxolone failed to prevent hypersensitivity induced by spinal cinnamaldehyde, a TRPA1 agonist. TRPA1 and DAAO mRNA in the DRG but not SDH were slightly increased in SNI, independent of drug treatment. The results indicate that prolonged peri-injury block of spinal TRPA1 or inhibition of spinal astrocyte activation attenuates maintenance but not development of mechanical (tactile allodynia-like) hypersensitivity after nerve injury.

Original languageEnglish
Pages (from-to)57-67
Number of pages11
JournalPHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume150-151
DOIs
Publication statusPublished - 1 Nov 2016
MoE publication typeA1 Journal article-refereed

Keywords

  • Astrocytes
  • D-Amino acid oxidase
  • Gabapentin
  • Hydrogen peroxide: Pain
  • Hypersensitivity
  • Spinal cord dorsal horn
  • TRPA1

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