Remote local photoactivation of morphine produces analgesia without opioid-related adverse effects.


Journal

British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536

Informations de publication

Date de publication:
04 2023
Historique:
revised: 19 07 2021
received: 07 01 2021
accepted: 23 07 2021
pubmed: 8 8 2021
medline: 4 3 2023
entrez: 7 8 2021
Statut: ppublish

Résumé

Opioid-based drugs are the gold standard medicines for pain relief. However, tolerance and several side effects (i.e. constipation and dependence) may occur upon chronic opioid administration. Photopharmacology is a promising approach to improve the benefit/risk profiles of these drugs. Thus, opioids can be locally activated with high spatiotemporal resolution, potentially minimizing systemic-mediated adverse effects. Here, we aimed at developing a morphine photo-derivative (photocaged morphine), which can be activated upon light irradiation both in vitro and in vivo. Light-dependent activity of pc-morphine was assessed in cell-based assays (intracellular calcium accumulation and electrophysiology) and in mice (formalin animal model of pain). In addition, tolerance, constipation and dependence were investigated in vivo using experimental paradigms. In mice, pc-morphine was able to elicit antinociceptive effects, both using external light-irradiation (hind paw) and spinal cord implanted fibre-optics. In addition, remote morphine photoactivation was devoid of common systemic opioid-related undesired effects, namely, constipation, tolerance to the analgesic effects, rewarding effects and naloxone-induced withdrawal. Light-dependent opioid-based drugs may allow effective analgesia without the occurrence of tolerance or the associated and severe opioid-related undesired effects. This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Sections du résumé

BACKGROUND AND PURPOSE
Opioid-based drugs are the gold standard medicines for pain relief. However, tolerance and several side effects (i.e. constipation and dependence) may occur upon chronic opioid administration. Photopharmacology is a promising approach to improve the benefit/risk profiles of these drugs. Thus, opioids can be locally activated with high spatiotemporal resolution, potentially minimizing systemic-mediated adverse effects. Here, we aimed at developing a morphine photo-derivative (photocaged morphine), which can be activated upon light irradiation both in vitro and in vivo.
EXPERIMENTAL APPROACH
Light-dependent activity of pc-morphine was assessed in cell-based assays (intracellular calcium accumulation and electrophysiology) and in mice (formalin animal model of pain). In addition, tolerance, constipation and dependence were investigated in vivo using experimental paradigms.
KEY RESULTS
In mice, pc-morphine was able to elicit antinociceptive effects, both using external light-irradiation (hind paw) and spinal cord implanted fibre-optics. In addition, remote morphine photoactivation was devoid of common systemic opioid-related undesired effects, namely, constipation, tolerance to the analgesic effects, rewarding effects and naloxone-induced withdrawal.
CONCLUSION AND IMPLICATIONS
Light-dependent opioid-based drugs may allow effective analgesia without the occurrence of tolerance or the associated and severe opioid-related undesired effects.
LINKED ARTICLES
This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Identifiants

pubmed: 34363210
doi: 10.1111/bph.15645
doi:

Substances chimiques

Morphine 76I7G6D29C
Analgesics, Opioid 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

958-974

Subventions

Organisme : Instituto de Salud Carlos III
ID : PIE14/00034
Organisme : Catalan government
ID : 2017 SGR 465
Organisme : Catalan government
ID : 2017 SGR 1604
Organisme : FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación
ID : CTQ2017-89222-R
Organisme : FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación
ID : SAF2017-87199-R
Organisme : FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación
ID : SAF2017-87349-R

Informations de copyright

© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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Auteurs

Marc López-Cano (M)

Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Joan Font (J)

MCS, Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.
Institut de Génomique Fonctionnelle (IGF), University of Montpellier, CNRS, INSERM, Montpellier, France.

Ester Aso (E)

Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Kristoffer Sahlholm (K)

Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.

Gisela Cabré (G)

Departament de Química, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.

Jesús Giraldo (J)

Laboratory of Molecular Neuropharmacology and Bioinformatics, Unitat de Bioestadística and Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Unitat de Neurociència Traslacional, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT), Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Barcelona, Spain.

Yves De Koninck (Y)

Institut Universitaire en Santé Mentale de Québec, Québec, Quebec, Canada.
Department of Psychiatry and Neuroscience, Université Laval, Québec, Quebec, Canada.

Jordi Hernando (J)

Departament de Química, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.

Amadeu Llebaria (A)

MCS, Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.

Víctor Fernández-Dueñas (V)

Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Francisco Ciruela (F)

Pharmacology Unit, Department of Pathology and Experimental Therapeutics, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Neuropharmacology & Pain Group, Neuroscience Program, Bellvitge Institute for Biomedical Research, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

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