@misc{10481/101001,
year = {2013},
month = {7},
url = {https://hdl.handle.net/10481/101001},
abstract = {We studied the modulation of morphine-induced mechanical antinociception and side effects by σ1 receptor inhibition. Both wild-type (WT) and σ1 receptor knockout (σ1-KO) mice showed similar responses to paw pressure (100–600 g). The systemic (subcutaneous) or local (intraplantar) administration of σ1 antagonists (BD-1063, BD-1047, NE-100 and S1RA) was devoid of antinociceptive effects in WT mice. However, σ1-KO mice exhibited an enhanced mechanical antinociception in response to systemic morphine (1–16 mg/kg). Similarly, systemic treatment of WT mice with σ1 antagonists markedly potentiated morphine-induced antinociception, and its effects were reversed by the selective σ1 agonist PRE-084. Although the local administration of morphine (50–200 μg) was devoid of antinociceptive effects in WT mice, it induced dose-dependent antinociception in σ1-KO mice. This effect was limited to the injected paw. Enhancement of peripheral morphine antinociception was replicated in WT mice locally co-administered with σ1 antagonists and the opioid. None of the σ1 antagonists tested enhanced morphine-antinociception in σ1-KO mice, confirming a σ1-mediated action. Morphine-induced side-effects (hyperlocomotion and inhibition of gastrointestinal transit) were unaltered in σ1-KO mice. These results cannot be explained by a direct interaction of σ1 ligands with μ-opioid receptors or adaptive changes of μ-receptors in σ1-KO mice, given that [3H]DAMGO binding in forebrain, spinal cord, and hind-paw skin membranes was unaltered in mutant mice, and none of the σ1 drugs tested bound to μ-opioid receptors. These results show that σ1 receptor inhibition potentiates morphine-induced mechanical analgesia but not its acute side effects, and that this enhanced analgesia can be induced at peripheral level.},
organization = {University of Granada},
organization = {Spanish Ministry of Education and Science (MEC) [grant SAF2006-06122]},
organization = {Junta de Andalucía [grant CTS 109]},
organization = {Laboratorios Esteve},
organization = {Spanish Government},
publisher = {Elsevier},
title = {Potentiation of morphine-induced mechanical antinociception by s1 receptor inhibition: Role of peripheral s1 receptors},
doi = {10.1016/j.neuropharm.2013.03.002},
author = {Sánchez-Fernández, Cristina and Nieto López, Francisco Rafael and González Cano, Rafael and Artacho Cordón, Antonia and Romero, Lucía and Montilla-García, Ángeles and Zamanillo, Daniel and Baeyens Cabrera, José Manuel and Entrena Fernández, José Manuel and Cobos del Moral, Enrique José},
}