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

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dc.contributor.author Wei, Hong
dc.contributor.author Wu, Hai-Yun
dc.contributor.author Chen, Zuyue
dc.contributor.author Ma, Ai-Niu
dc.contributor.author Mao, Xiao-Fang
dc.contributor.author Li, Teng-Fei
dc.contributor.author Li, Xin-Yan
dc.contributor.author Wang, Yong-Xiang
dc.contributor.author Pertovaara, Antti
dc.date.accessioned 2018-01-18T22:07:56Z
dc.date.available 2021-12-17T18:47:51Z
dc.date.issued 2016
dc.identifier.citation 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
dc.identifier.other PURE: 78370896
dc.identifier.other PURE UUID: c9a599b9-55a7-42ec-85ba-ff7ebdcd1572
dc.identifier.other WOS: 000390084500008
dc.identifier.other Scopus: 84988945151
dc.identifier.other ORCID: /0000-0002-8590-7220/work/29948056
dc.identifier.uri http://hdl.handle.net/10138/231311
dc.description.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. en
dc.format.extent 11
dc.language.iso eng
dc.relation.ispartof Pharmacology, Biochemistry and Behavior
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Astrocytes
dc.subject D-Amino acid oxidase
dc.subject Gabapentin
dc.subject Hydrogen peroxide: Pain
dc.subject Hypersensitivity
dc.subject Spinal cord dorsal horn
dc.subject TRPA1
dc.subject INDUCED TONIC PAIN
dc.subject RECEPTOR POTENTIAL A1
dc.subject NERVE INJURY
dc.subject DORSAL-HORN
dc.subject ION-CHANNEL
dc.subject D-SERINE
dc.subject COLD HYPERSENSITIVITY
dc.subject POSTOPERATIVE PAIN
dc.subject SLEEP-DEPRIVATION
dc.subject DIABETIC ANIMALS
dc.subject 3111 Biomedicine
dc.title Mechanical antihypersensitivity effect induced by repeated spinal administrations of a TRPA1 antagonist or a gap junction decoupler in peripheral neuropathy en
dc.type Article
dc.contributor.organization Medicum
dc.contributor.organization Department of Physiology
dc.contributor.organization Antti Pertovaara / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.pbb.2016.09.007
dc.relation.issn 0091-3057
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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