Characterization of New TRPM8 Modulators in Pain Perception

Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to redu...

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Detalhes bibliográficos
Autores: De Caro, C., Cristiano, C., Avagliano, C., Bertamino, A., Ostacolo, C., Campiglia, P., Gomez-Monterrey, I., La Rana, G., Gualillo ., Oreste, Calignano, A., Russo, R.
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/15414
Acesso em linha:https://www.ncbi.nlm.nih.gov/pubmed/31703254
http://hdl.handle.net/20.500.11940/15414
Access Level:acceso abierto
Palavra-chave:Pain Perception
Rats
Analgesics
Mice
Pain
TRPM Cation Channels
Animals
dolor
animales
analgésicos
percepción del dolor
canales catiónicos TRPM
ratas
ratones
IDIS
CHUS
id ES_43af21df541a287b9237eaeb8dc0ecc6
oai_identifier_str oai:runa.sergas.gal:20.500.11940/15414
network_acronym_str ES
network_name_str España
repository_id_str
spelling Characterization of New TRPM8 Modulators in Pain PerceptionDe Caro, C.Cristiano, C.Avagliano, C.Bertamino, A.Ostacolo, C.Campiglia, P.Gomez-Monterrey, I.La Rana, G.Gualillo ., OresteCalignano, A.Russo, R.Pain PerceptionRatsAnalgesicsMicePainTRPM Cation ChannelsAnimalsdoloranimalesanalgésicospercepción del dolorcanales catiónicos TRPMratasratonesIDISCHUSBackground: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.2019info:eu-repo/semantics/articlehttps://www.ncbi.nlm.nih.gov/pubmed/31703254http://hdl.handle.net/20.500.11940/15414reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/154142026-06-12T08:40:47Z
dc.title.none.fl_str_mv Characterization of New TRPM8 Modulators in Pain Perception
title Characterization of New TRPM8 Modulators in Pain Perception
spellingShingle Characterization of New TRPM8 Modulators in Pain Perception
De Caro, C.
Pain Perception
Rats
Analgesics
Mice
Pain
TRPM Cation Channels
Animals
dolor
animales
analgésicos
percepción del dolor
canales catiónicos TRPM
ratas
ratones
IDIS
CHUS
title_short Characterization of New TRPM8 Modulators in Pain Perception
title_full Characterization of New TRPM8 Modulators in Pain Perception
title_fullStr Characterization of New TRPM8 Modulators in Pain Perception
title_full_unstemmed Characterization of New TRPM8 Modulators in Pain Perception
title_sort Characterization of New TRPM8 Modulators in Pain Perception
dc.creator.none.fl_str_mv De Caro, C.
Cristiano, C.
Avagliano, C.
Bertamino, A.
Ostacolo, C.
Campiglia, P.
Gomez-Monterrey, I.
La Rana, G.
Gualillo ., Oreste
Calignano, A.
Russo, R.
author De Caro, C.
author_facet De Caro, C.
Cristiano, C.
Avagliano, C.
Bertamino, A.
Ostacolo, C.
Campiglia, P.
Gomez-Monterrey, I.
La Rana, G.
Gualillo ., Oreste
Calignano, A.
Russo, R.
author_role author
author2 Cristiano, C.
Avagliano, C.
Bertamino, A.
Ostacolo, C.
Campiglia, P.
Gomez-Monterrey, I.
La Rana, G.
Gualillo ., Oreste
Calignano, A.
Russo, R.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Pain Perception
Rats
Analgesics
Mice
Pain
TRPM Cation Channels
Animals
dolor
animales
analgésicos
percepción del dolor
canales catiónicos TRPM
ratas
ratones
IDIS
CHUS
topic Pain Perception
Rats
Analgesics
Mice
Pain
TRPM Cation Channels
Animals
dolor
animales
analgésicos
percepción del dolor
canales catiónicos TRPM
ratas
ratones
IDIS
CHUS
description Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.ncbi.nlm.nih.gov/pubmed/31703254
http://hdl.handle.net/20.500.11940/15414
url https://www.ncbi.nlm.nih.gov/pubmed/31703254
http://hdl.handle.net/20.500.11940/15414
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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