Wei , H , Chen , Z , Koivisto , A & Pertovaara , A 2021 , ' Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat ' , Pharmacological Reports , vol. 73 , no. 2 , pp. 672-679 . https://doi.org/10.1007/s43440-020-00207-x
Title: | Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat |
Author: | Wei, Hong; Chen, Zuyue; Koivisto, Ari; Pertovaara, Antti |
Contributor organization: | Department of Physiology Faculty of Medicine Antti Pertovaara / Principal Investigator |
Date: | 2021-04 |
Language: | eng |
Number of pages: | 8 |
Belongs to series: | Pharmacological Reports |
ISSN: | 1734-1140 |
DOI: | https://doi.org/10.1007/s43440-020-00207-x |
URI: | http://hdl.handle.net/10138/340115 |
Abstract: | Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, sigma(1) and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (sigma(1) receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the sigma(1) and NMDA receptors, and DAAO. |
Subject: |
Gap junction
Pain hypersensitivity δ receptor Sphingolipids Spinal cord TRPM3 SLEEP-DEPRIVATION RECEPTOR ACTIVATION PATHWAY 317 Pharmacy |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
Total number of downloads: Loading...
Files | Size | Format | View |
---|---|---|---|
Wei2021_Article_SpinalMechanismsContributingTo.pdf | 602.1Kb |
View/ |