@misc{10498/17865,
year = {2013},
month = {1},
url = {http://hdl.handle.net/10498/17865},
abstract = {Tapentadol is a novel centrally acting drug that combines mu-opioid receptor (MOR) agonism and
noradrenaline reuptake inhibition (NRI), producing analgesic effects in various painful conditions. We
investigated the acute effects of tapentadol in the locus coeruleus (LC), a central nucleus regulated by the
noradrenergic and opioid systems that is critical in pain modulation. In single-unit extracellular recordings
of LC neurons from anaesthetized male SpragueeDawley rats, tapentadol clearly inhibited the
spontaneous electrophysiological activity of LC neurons in a dose-dependent manner (ED50 ¼ 0.8 mg/kg).
This inhibitory effect was reversed by RX821002 (an alpha2-adrenoceptor antagonist) and naloxone (a
mu-opioid receptor antagonist) by 96.7% and 28.2%, respectively. Pretreatment with RX821002, Nethoxycarbonyl-
2-ethoxy-1-2-dihydroquinoline (EEDQ, an irreversible alpha2-adrenoceptor antagonist)
or naloxone shifted the tapentadol doseeeffect curve to the right (ED50 ¼ 2.2 mg/kg, 2.0 mg/kg and
2.1 mg/kg, respectively). Furthermore, tapentadol inhibited the LC response to mechanical stimulation of
the hindpaw in a dose-dependent manner. In summary, we demonstrate that acute administration of
tapentadol inhibits LC neurons in vivo, mainly due to the activation of alpha2-adrenoceptors. These data
suggest that both the noradrenergic and opioid systems participate in the inhibitory effect of tapentadol
on LC neurons, albeit to different extents, which may account for its potent analgesic effect and mild
opioidergic side-effects.},
organization = {This study was supported by grants from Grünenthal GmbH
(OT2010/075); “Fondo de Investigación Sanitaria” (PI10/01221 and
PI12/00915); CIBERSAM (G18); Junta de Andalucía, Consejería de
Innovación, Ciencia y Empresa (CTS-510, CTS-4303 and CTS-7748);
Cátedra Externa del Dolor Grünenthal-Universidad de Cádiz;
FP7-PEOPLE-2010-RG (268377); FPU (AP2007-02397) and FPI
(2011-145) fellowships},
keywords = {Tapentadol},
keywords = {Opioid receptor},
keywords = {Alpha2-adrenoceptor},
keywords = {Locus coeruleus},
keywords = {Desipramine},
keywords = {Morphine},
title = {Effect of tapentadol on neurons in the locus coeruleus},
doi = {10.1016/j.neuropharm.2013.04.053},
author = {Torres Sánchez, Sonia and Alba Delgado, Cristina and Llorca Torralba, Meritxell and Micó Segura, Juan Antonio and Berrocoso Domínguez, Esther María},
}