Remote local photoactivation of morphine produces analgesia without opioid-related adverse effects
López Cano, Marc (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Font Inglès, Joan (Institut de Química Avançada de Catalunya)
Aso, Ester (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Sahlholm, Kristoffer (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Cabré Segura, Gisela (Universitat Autònoma de Barcelona. Departament de Química)
Giraldo, Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
De Koninck, Yves (Université Laval. Department of Psychiatry and Neuroscience)
Hernando Campos, Jordi (Universitat Autònoma de Barcelona. Departament de Química)
Llebaria, Amadeu (Institut de Química Avançada de Catalunya)
Fernández-Dueñas, Víctor (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)
Ciruela, Francisco (Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental)

Date:	2021
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PIE14/00034 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-465 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1604 Agencia Estatal de Investigación CTQ2017-89222-R Agencia Estatal de Investigación SAF2017-87199-R Agencia Estatal de Investigación SAF2017-87349-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Dependence ; Morphine ; Pain ; Photopharmacology ; Tolerance
Published in:	British Journal of Pharmacology, 2021 , ISSN 1476-5381

DOI: 10.1111/bph.15645
PMID: 34363210

18 p, 5.7 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Group in Electrochemistry, Photochemistry and Organic Reactivity (GEFRO)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles