Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

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dc.contributor.author Wei, Hong
dc.contributor.author Chen, Zuyue
dc.contributor.author Koivisto, Ari
dc.contributor.author Pertovaara, Antti
dc.date.accessioned 2022-02-11T11:43:03Z
dc.date.available 2022-02-11T11:43:03Z
dc.date.issued 2021-04
dc.identifier.citation 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
dc.identifier.other PURE: 160094229
dc.identifier.other PURE UUID: 8a4be6e2-bd29-4b98-bfeb-3416d616f5c5
dc.identifier.other WOS: 000604508800007
dc.identifier.other ORCID: /0000-0002-8590-7220/work/108068430
dc.identifier.uri http://hdl.handle.net/10138/340115
dc.description.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. en
dc.format.extent 8
dc.language.iso eng
dc.relation.ispartof Pharmacological Reports
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Gap junction
dc.subject Pain hypersensitivity
dc.subject &#948
dc.subject receptor
dc.subject Sphingolipids
dc.subject Spinal cord
dc.subject TRPM3
dc.subject SLEEP-DEPRIVATION
dc.subject RECEPTOR
dc.subject ACTIVATION
dc.subject PATHWAY
dc.subject 317 Pharmacy
dc.title Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat en
dc.type Article
dc.contributor.organization Department of Physiology
dc.contributor.organization Faculty of Medicine
dc.contributor.organization Antti Pertovaara / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1007/s43440-020-00207-x
dc.relation.issn 1734-1140
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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