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

TitleRemote local photoactivation of morphine produces analgesia without opioid-related adverse effects.
Publication TypeJournal Article
Year of Publication2021
AuthorsLópez-Cano, M, Font, J, Aso, E, Sahlholm, K, Cabré, G, Giraldo, J, De Koninck, Y, Hernando, J, Llebaria, A, Fernández-Dueñas, V, Ciruela, F
JournalBr J Pharmacol
Date Published2021 Aug 06
ISSN1476-5381
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.

DOI10.1111/bph.15645
Alternate JournalBr J Pharmacol
PubMed ID34363210
Grant ListPIE14/00034 / / Instituto de Salud Carlos III /
2017 SGR 465 / / Catalan government /
2017 SGR 1604 / / Catalan government /
CTQ2017-89222-R / / FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación /
SAF2017-87199-R / / FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación /
SAF2017-87349-R / / FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación /