Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain

People with chronic pain mitigate their suffering by the action of opioids. Adverse reactions aside, opioids are not exempt from potential complications like addiction and abuse, which have posed a global public health problem lately. Finding new therapeutic strategies to improve analgesia and to re...

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Autores: Paniagua, N., García, M. M, Rodríguez Rivera, C., Pascual, D., Herradón, E., González, A., Molina-Álvarez, M., Goicoechea, C., López-Miranda, V., Sánchez-Robles, E. M., Girón, R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/374864
Acceso en línea:http://hdl.handle.net/10261/374864
Access Level:acceso abierto
Palabra clave:Opioid
Antidepressant
Musculoskeletal pain
Clusterin
Sex dimorphism
Rat
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spelling Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic painPaniagua, N.García, M. MRodríguez Rivera, C.Pascual, D.Herradón, E.González, A.Molina-Álvarez, M.Goicoechea, C.López-Miranda, V.Sánchez-Robles, E. M.Girón, R.OpioidAntidepressantMusculoskeletal painClusterinSex dimorphismRatPeople with chronic pain mitigate their suffering by the action of opioids. Adverse reactions aside, opioids are not exempt from potential complications like addiction and abuse, which have posed a global public health problem lately. Finding new therapeutic strategies to improve analgesia and to reduce opioid side effects has become a priority. In this regard, the association of different adjuvant therapies has been postulated. Despite preclinical and clinical evidence supporting the use of antidepressants as analgesics, it is not clear whether they could help reduce the risk of addiction in combination with opioids. To further explore this idea a model of chronic osteoarthritis pain was employed, and a combination of mirtazapine and morphine was used in a chronic regimen in male and female rats. The effects on the development of tactile allodynia, movement-evoked pain, reward, analgesic tolerance, naloxone-induced withdrawal symptoms, impaired locomotor activity and anxiety were evaluated under a 25-day experimental protocol. Additionally, protein expression of μ-opioid receptors and clusterin (related with substance abuse) was evaluated in plasma and in brain structures of the reward system. Chronic morphine caused analgesic tolerance, reward and naloxone-induced withdrawal symptoms. The combination reduced the analgesic tolerance and prevented the development of withdrawal symptoms but showed sex-based differences regarding reward. Increased levels of clusterin in plasma were observed in females treated with morphine, but not with combined therapy. The combination of mirtazapine and morphine could be a promising strategy to improve the management of long-term opioid treatment and its risk of abuse, especially in females.This work has been supported by the Government Delegation for the National Drugs Plan of the Ministry of Health of the Spanish Government (2020I062). The authors declare no conflict of interest.ElsevierMinisterio de Sanidad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/374864reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.ejphar.2024.177165Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3748642026-05-22T06:33:51Z
dc.title.none.fl_str_mv Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
title Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
spellingShingle Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
Paniagua, N.
Opioid
Antidepressant
Musculoskeletal pain
Clusterin
Sex dimorphism
Rat
title_short Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
title_full Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
title_fullStr Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
title_full_unstemmed Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
title_sort Modulation of morphine antinociceptive and rewarding effect by mirtazapine in an animal model of osteoarthritic pain
dc.creator.none.fl_str_mv Paniagua, N.
García, M. M
Rodríguez Rivera, C.
Pascual, D.
Herradón, E.
González, A.
Molina-Álvarez, M.
Goicoechea, C.
López-Miranda, V.
Sánchez-Robles, E. M.
Girón, R.
author Paniagua, N.
author_facet Paniagua, N.
García, M. M
Rodríguez Rivera, C.
Pascual, D.
Herradón, E.
González, A.
Molina-Álvarez, M.
Goicoechea, C.
López-Miranda, V.
Sánchez-Robles, E. M.
Girón, R.
author_role author
author2 García, M. M
Rodríguez Rivera, C.
Pascual, D.
Herradón, E.
González, A.
Molina-Álvarez, M.
Goicoechea, C.
López-Miranda, V.
Sánchez-Robles, E. M.
Girón, R.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Sanidad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Opioid
Antidepressant
Musculoskeletal pain
Clusterin
Sex dimorphism
Rat
topic Opioid
Antidepressant
Musculoskeletal pain
Clusterin
Sex dimorphism
Rat
description People with chronic pain mitigate their suffering by the action of opioids. Adverse reactions aside, opioids are not exempt from potential complications like addiction and abuse, which have posed a global public health problem lately. Finding new therapeutic strategies to improve analgesia and to reduce opioid side effects has become a priority. In this regard, the association of different adjuvant therapies has been postulated. Despite preclinical and clinical evidence supporting the use of antidepressants as analgesics, it is not clear whether they could help reduce the risk of addiction in combination with opioids. To further explore this idea a model of chronic osteoarthritis pain was employed, and a combination of mirtazapine and morphine was used in a chronic regimen in male and female rats. The effects on the development of tactile allodynia, movement-evoked pain, reward, analgesic tolerance, naloxone-induced withdrawal symptoms, impaired locomotor activity and anxiety were evaluated under a 25-day experimental protocol. Additionally, protein expression of μ-opioid receptors and clusterin (related with substance abuse) was evaluated in plasma and in brain structures of the reward system. Chronic morphine caused analgesic tolerance, reward and naloxone-induced withdrawal symptoms. The combination reduced the analgesic tolerance and prevented the development of withdrawal symptoms but showed sex-based differences regarding reward. Increased levels of clusterin in plasma were observed in females treated with morphine, but not with combined therapy. The combination of mirtazapine and morphine could be a promising strategy to improve the management of long-term opioid treatment and its risk of abuse, especially in females.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2025
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/10261/374864
url http://hdl.handle.net/10261/374864
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.ejphar.2024.177165
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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