Venue: Centre Broca
Antonio Ferrer-Montiel
IDIBE – Universidate Miguel Hernandez
Elche (Alicante), Spain
Invited by Marc Landry (IMN)
Title
ThermoTRPs in Chronic Migraine and its Sex Dimorphism
Abstract
TRPA1 and TRPM8 are transient receptor potential channels expressed in trigeminal neurons, implicated in the pathophysiology of migraine. We developed a mouse model of nitroglycerine-induced chronic migraine exhibiting a sexually dimorphic phenotype. Both male and female mice developed mechanical hypersensitivity; however, this condition persisted up to day 20 in females, while it resolved by day 18 in males. The development of hypersensitivity required TRPA1 in both sexes, whereas TRPM8 facilitated more rapid recovery in males. The antinociceptive effects mediated by TRPM8 depended on endogenous testosterone in male mice. Administration of exogenous testosterone to females and orchiectomized males resulted in alleviation of hypersensitivity. Notably, testosterone ionotropically activated murine and human TRPM8. These findings suggest a protective role of a testosterone-mediated activation of TRPM8 in reducing the duration of hypersensitivity in migraine.
Selected publications
- Cabañero D, Carter EP, González-Cano R, Cobos EJ, Fernández-Carvajal A, Ferrer-Montiel A Cold receptor TRPM8 as a target for migraine-associated pain and affective comorbidities. J Headache Pain. 2025 Jun 23;26(1):146. doi: 10.1186/s10194-025-02082-4.
- Alarcón-Alarcón D, Cabañero D, Andrés-López J, Nikolaeva-Koleva M, Giorgi S, Fernández-Ballester G, Fernández-Carvaja A, Ferrer-Montiel A. TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine. Nat. Commun. 2022, 13, 6304.
- Cabañero D, Villalba-Riquelme E, Fernández-Ballester G, Fernández-Carvajal A, Ferrer-Montiel A. ThermoTRP channels in pain sexual dimorphism: new insights for drug intervention. Pharmacol Ther. 2022 Dec;240:108297.
- Villalba-Riquelme E, de la Torre-Martínez R, Fernández-Carvajal A, Ferrer-Montiel A. Oxaliplatin reversibly and differentially affects electrogenic activity of small IB4(+) of male and female rat sensory neurons. Biomed Pharmacother. 2025 Feb;183:117849. doi: 10.1016/j.biopha.2025.117849.
- Hingorani S, Paniagua Soriano G, Sánchez Huertas C, Villalba Riquelme EM, López Mocholi E, Martínez Rojas B, Alastrué Agudo A, Dupraz S, Ferrer Montiel A, Moreno Manzano V. Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI. Mol Ther. 2024 Mar 30:S1525-0016(24)00216-8. doi: 10.1016/j.ymthe.2024.03.038.
- Giorgi S, Lamberti A, Butrón L, Gross-Amat O, Alarcón-Alarcón D, Rodríguez-Cañas E, Fernández-Carvajal A, Ferrer-Montiel A. Compartmentalized primary cultures of dorsal root ganglion neurons to model peripheral pathophysiological conditions. Mol Pain. 2023 Jan-Dec;19:17448069231197102.