The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.

Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The...

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Authors: Falo, CP, Benitez, Raquel, Caro, Marta, Morell, María, Forte-Lago, Irene, Hernández-Cortés, Pedro, Sánchez-González, Clara, O'Valle, Francisco, Delgado, Mario, González-Rey, Elena
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/359499
Online Access:http://hdl.handle.net/10261/359499
Access Level:Open access
Keyword:neuropathic pain
neuropeptide
neuroprotection
neuroregeneration
peripheral nerve injury
neuroinflammation
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spelling The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.Falo, CPBenitez, RaquelCaro, MartaMorell, MaríaForte-Lago, IreneHernández-Cortés, PedroSánchez-González, ClaraO'Valle, FranciscoDelgado, MarioGonzález-Rey, Elenaneuropathic painneuropeptideneuroprotectionneuroregenerationperipheral nerve injuryneuroinflammationNeuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.This study was mainly supported by the Spanish Ministry of Science and Innovation (MICINN, grant SAF2014-58354-R and SAF2017-85602-R for E.G-R.) and the Andalucian Regional Government (Grants of Excellence for M.D.). R.B. was the recipient of the FPI fellowship from MICINN.Ministerio de Ciencia e Innovación (España)Junta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420212024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/359499reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/pharmaceutics13070947Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3594992026-05-22T06:33:51Z
dc.title.none.fl_str_mv The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
title The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
spellingShingle The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
Falo, CP
neuropathic pain
neuropeptide
neuroprotection
neuroregeneration
peripheral nerve injury
neuroinflammation
title_short The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
title_full The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
title_fullStr The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
title_full_unstemmed The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
title_sort The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury.
dc.creator.none.fl_str_mv Falo, CP
Benitez, Raquel
Caro, Marta
Morell, María
Forte-Lago, Irene
Hernández-Cortés, Pedro
Sánchez-González, Clara
O'Valle, Francisco
Delgado, Mario
González-Rey, Elena
author Falo, CP
author_facet Falo, CP
Benitez, Raquel
Caro, Marta
Morell, María
Forte-Lago, Irene
Hernández-Cortés, Pedro
Sánchez-González, Clara
O'Valle, Francisco
Delgado, Mario
González-Rey, Elena
author_role author
author2 Benitez, Raquel
Caro, Marta
Morell, María
Forte-Lago, Irene
Hernández-Cortés, Pedro
Sánchez-González, Clara
O'Valle, Francisco
Delgado, Mario
González-Rey, Elena
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv neuropathic pain
neuropeptide
neuroprotection
neuroregeneration
peripheral nerve injury
neuroinflammation
topic neuropathic pain
neuropeptide
neuroprotection
neuroregeneration
peripheral nerve injury
neuroinflammation
description Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.
publishDate 2021
dc.date.none.fl_str_mv 2021
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/359499
url http://hdl.handle.net/10261/359499
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/pharmaceutics13070947
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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