β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models
Transient 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 mod ulators le...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad Miguel Hernández de Elche |
| Repositorio: | REDIUMH. Depósito Digital de la UMH |
| OAI Identifier: | oai:dspace.umh.es:11000/34395 |
| Acceso en línea: | https://hdl.handle.net/11000/34395 |
| Access Level: | acceso abierto |
| Palabra clave: | TRPM8 channels antagonist β–lactam oxaliplatin-induced peripheral neuropathy CCI chronic neuropathic nociception NTG-induced hyperesthesia CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica |
| id |
ES_6f67bc91c2b755542dd68ed6624aeddc |
|---|---|
| oai_identifier_str |
oai:dspace.umh.es:11000/34395 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal ModelsMartín Escura, CristinaMedina Peris, AliciaSpear, Lukede la Torre-Martinez, RobertoOlivos-Oré, Luis A.Barahona, M. VictoriaGonzález-Rodríguez, SaraFernandez-Ballester, GregorioFernandez-Carvajal, AsiaArtalejo, Antonio R.Ferrer-Montiel, AntonioGONZALEZ-MUÑIZ, ROSARIOTRPM8 channelsantagonistβ–lactamoxaliplatin-induced peripheral neuropathyCCI chronic neuropathicnociceptionNTG-induced hyperesthesiaCDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. BiofísicaTransient 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 mod ulators 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.MDPIDepartamentos de la UMH::Bioquímica y Biología Molecular202520252022info:eu-repo/semantics/articleapplication/pdf24application/pdfhttps://hdl.handle.net/11000/34395reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheInglés23https://doi.org/10.3390/ijms23052692info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dspace.umh.es:11000/343952026-05-27T13:36:21Z |
| dc.title.none.fl_str_mv |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models |
| title |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models |
| spellingShingle |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models Martín Escura, Cristina TRPM8 channels antagonist β–lactam oxaliplatin-induced peripheral neuropathy CCI chronic neuropathic nociception NTG-induced hyperesthesia CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica |
| title_short |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models |
| title_full |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models |
| title_fullStr |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models |
| title_full_unstemmed |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models |
| title_sort |
β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models |
| dc.creator.none.fl_str_mv |
Martín Escura, Cristina Medina Peris, Alicia Spear, Luke de la Torre-Martinez, Roberto Olivos-Oré, Luis A. Barahona, M. Victoria González-Rodríguez, Sara Fernandez-Ballester, Gregorio Fernandez-Carvajal, Asia Artalejo, Antonio R. Ferrer-Montiel, Antonio GONZALEZ-MUÑIZ, ROSARIO |
| author |
Martín Escura, Cristina |
| author_facet |
Martín Escura, Cristina Medina Peris, Alicia Spear, Luke de la Torre-Martinez, Roberto Olivos-Oré, Luis A. Barahona, M. Victoria González-Rodríguez, Sara Fernandez-Ballester, Gregorio Fernandez-Carvajal, Asia Artalejo, Antonio R. Ferrer-Montiel, Antonio GONZALEZ-MUÑIZ, ROSARIO |
| author_role |
author |
| author2 |
Medina Peris, Alicia Spear, Luke de la Torre-Martinez, Roberto Olivos-Oré, Luis A. Barahona, M. Victoria González-Rodríguez, Sara Fernandez-Ballester, Gregorio Fernandez-Carvajal, Asia Artalejo, Antonio R. Ferrer-Montiel, Antonio GONZALEZ-MUÑIZ, ROSARIO |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamentos de la UMH::Bioquímica y Biología Molecular |
| dc.subject.none.fl_str_mv |
TRPM8 channels antagonist β–lactam oxaliplatin-induced peripheral neuropathy CCI chronic neuropathic nociception NTG-induced hyperesthesia CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica |
| topic |
TRPM8 channels antagonist β–lactam oxaliplatin-induced peripheral neuropathy CCI chronic neuropathic nociception NTG-induced hyperesthesia CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica |
| description |
Transient 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 mod ulators 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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11000/34395 |
| url |
https://hdl.handle.net/11000/34395 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
23 https://doi.org/10.3390/ijms23052692 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.format.none.fl_str_mv |
application/pdf 24 application/pdf |
| dc.publisher.none.fl_str_mv |
MDPI |
| publisher.none.fl_str_mv |
MDPI |
| dc.source.none.fl_str_mv |
reponame:REDIUMH. Depósito Digital de la UMH instname:Universidad Miguel Hernández de Elche |
| instname_str |
Universidad Miguel Hernández de Elche |
| reponame_str |
REDIUMH. Depósito Digital de la UMH |
| collection |
REDIUMH. Depósito Digital de la UMH |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869410493791207424 |
| score |
15,811543 |