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

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Wei , H , Wu , H-Y , Chen , Z , Ma , A-N , Mao , X-F , Li , T-F , Li , X-Y , Wang , Y-X & Pertovaara , A 2016 , ' Mechanical antihypersensitivity effect induced by repeated spinal administrations of a TRPA1 antagonist or a gap junction decoupler in peripheral neuropathy ' , Pharmacology, Biochemistry and Behavior , vol. 150 , pp. 57-67 . https://doi.org/10.1016/j.pbb.2016.09.007

Title: Mechanical antihypersensitivity effect induced by repeated spinal administrations of a TRPA1 antagonist or a gap junction decoupler in peripheral neuropathy
Author: Wei, Hong; Wu, Hai-Yun; Chen, Zuyue; Ma, Ai-Niu; Mao, Xiao-Fang; Li, Teng-Fei; Li, Xin-Yan; Wang, Yong-Xiang; Pertovaara, Antti
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Medicum
Date: 2016
Language: eng
Number of pages: 11
Belongs to series: Pharmacology, Biochemistry and Behavior
ISSN: 0091-3057
URI: http://hdl.handle.net/10138/231311
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. (C) 2016 Elsevier Inc. All rights reserved.
Subject: Astrocytes
D-Amino acid oxidase
Gabapentin
Hydrogen peroxide: Pain
Hypersensitivity
Spinal cord dorsal horn
TRPA1
INDUCED TONIC PAIN
RECEPTOR POTENTIAL A1
NERVE INJURY
DORSAL-HORN
ION-CHANNEL
D-SERINE
COLD HYPERSENSITIVITY
POSTOPERATIVE PAIN
SLEEP-DEPRIVATION
DIABETIC ANIMALS
3111 Biomedicine
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