Martín Escura, CristinaMedina Peris, AliciaSpear, Luke A.de la Torre Martínez, RobertoOlivos Ore, Luis AlcidesBarahona Gomáriz, María VictoriaGonzález Rodríguez de Castro, SaraFernández Ballester, GregorioFernández Carvajal, AsiaRodríguez Artalejo, AntonioFerrer Montiel, AntonioGonzález Muñiz, Rosario2023-06-222023-06-222022-02-281422-006710.3390/ijms23052692https://hdl.handle.net/20.500.14352/72502Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a β–lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors. In primary cultures of rat dorsal root ganglion (DRG) neurons, RGM8-51 potently reduced menthol-evoked neuronal firing without affecting the major ion conductances responsible for action potential generation. This compound has in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy. In addition, it reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve. Furthermore, RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia. Taken together, these preclinical results substantiate that this TRPM8 antagonist is a promising pharmacological tool to study TRPM8-related diseases.engAtribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/journal articlehttps://doi.org/10.3390/ijms23052692https://www.mdpi.com/1422-0067/23/5/2692?type=check_update&version=3open accessTRPM8 channelsantagonistβ–lactamoxaliplatin-induced peripheral neuropathyCCI chronic neuropathicnociceptionNTG-induced hyperesthesiaFarmacología veterinaria3109.08 Farmacología