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

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Pysyväisosoite

http://hdl.handle.net/10138/340115

Lähdeviite

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

Julkaisun nimi: Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat
Tekijä: Wei, Hong; Chen, Zuyue; Koivisto, Ari; Pertovaara, Antti
Tekijän organisaatio: Department of Physiology
Faculty of Medicine
Antti Pertovaara / Principal Investigator
Päiväys: 2021-04
Kieli: eng
Sivumäärä: 8
Kuuluu julkaisusarjaan: Pharmacological Reports
ISSN: 1734-1140
DOI-tunniste: https://doi.org/10.1007/s43440-020-00207-x
URI: http://hdl.handle.net/10138/340115
Tiivistelmä: 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.
Avainsanat: Gap junction
Pain hypersensitivity
&#948
receptor
Sphingolipids
Spinal cord
TRPM3
SLEEP-DEPRIVATION
RECEPTOR
ACTIVATION
PATHWAY
317 Pharmacy
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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