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Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model

Á. Horváth, A. Steib, A. Nehr-Majoros, B. Kántás, Á. Király, M. Racskó, BI. Tóth, E. Szánti-Pintér, E. Kudová, R. Skoda-Földes, Z. Helyes, É. Szőke

. 2024 ; 25 (9) : . [pub] 20240424

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24014260

Grant support
134725 National Research, Development and Innovation Office
GINOP-2.3.2-15-2016-00050 National Research, Development and Innovation Office
TKP2021-EGA-13 National Research, Development and Innovation Fund of Hungary
TKP2021-EGA-16 National Research, Development and Innovation Fund of Hungary
PTE-ÁOK-KA-2021-09 University of Pecs
NKFIH-138936 National Research, Development and Innovation Office
HUN-REN-PTE Chronic Pain Research Group
Phar-maLab, RRF-2.3.1-21-2022-00015 The National Research, Development and Innovation Office
LX22NPO5104 National Institute for Research of Metabolic and Cardiovascular Diseases
Next Generation EU European Union
RVO:61388963 Czech Academy of Sciences
ÚNKP-22-3-I-DE-324 Ministry for Innovation and Technology

The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions.

References provided by Crossref.org

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