Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice

Abstract

Background: Febrile seizures (FSs) are the most frequent type of seizures in infancy and childhood. Epileptiform discharges (EDs) on electroencephalogram at the time of first FS recurrence can increase the risk of epilepsy development. Therefore, inhibition of EDs is important. Recently, WS-3, a transient receptor potential melastatin 8 (TRPM8) agonist, reportedly suppressed penicillin G-induced cortical-focal EDs. However, the effects of TRPM8 agonists on FSs remain unknown. In this study, we aimed to clarify the effects of the TRPM8 agonist, and the absence of TRPM8 channels, on hyperthermia-induced FS by analyzing the fast ripple band.Methods: Hyperthermia (43°C for 30 min) induced by a heating pad caused FSs in postnatal day 7 wild-type (WT) and TRPM8 knockout (TRPM8KO) mice. FSs were defined as EDs occurring during behavioral seizures involving hindlimb clonus and loss of the righting reflex. Mice were injected with 1% dimethyl sulfoxide or 1 mM WS-3 20 min before the onset of hyperthermia, and electroencephalograms; movies; and rectal, brain and heating pad temperatures were recorded.Results: In wild-type mice, WS-3 reduced the fast ripple amplitude in the first FS without changing rectal and brain temperature thresholds. In contrast, the anti-FS effect induced by the TRPM8 agonist was not observed in TRPM8KO mice and, compared with wild-type mice, TRPM8 deficiency lowered the rectal and brain temperature thresholds for FSs, exacerbated the fast ripple amplitude, and prolonged the duration of the initial FS induced by hyperthermia.Conclusion: Our findings suggest that TRPM8 agonists can be used to treat hyperthermia-induced FSs.

Genetic and immune identification and functional analysis of TRPM8 as a potential biomarker for pancreatic adenocarcinoma proliferation

“… 38 Additionally, scientific evidence has substantiated the pain‐relieving properties of menthol in countering chemical stimulation and inflammation through a TRPM8‐dependent mechanism. 39 , 40 , 41 Notably, the absence of analgesic effects of menthol in TRPM8 knockout mice and the complete absence of analgesia induced by WS‐12 (a selective TRPM8 agonist) further support these findings. 42 , 43 The potential antimigraine properties of butterbur may be attributed to the selective activation of the TRPA1 channel by Isopetasin, the primary constituent of its extract, leading to subsequent notable neuronal desensitization.…”

“…Furthermore, empirical research has demonstrated that the utilization of a high concentration (8%) capsaicin patch yields significant pain alleviation for individuals experiencing postherpes zoster pain and nerve injury pain associated with HIV infection 38 . Additionally, scientific evidence has substantiated the pain‐relieving properties of menthol in countering chemical stimulation and inflammation through a TRPM8‐dependent mechanism 39–41 . Notably, the absence of analgesic effects of menthol in TRPM8 knockout mice and the complete absence of analgesia induced by WS‐12 (a selective TRPM8 agonist) further support these findings 42,43 .…”