RT journal article
T1 Effect of tapentadol on neurons in the locus coeruleus
A1 Torres Sánchez, Sonia
A1 Alba Delgado, Cristina
A1 Llorca Torralba, Meritxell
A1 Micó Segura, Juan Antonio
A1 Berrocoso Domínguez, Esther María
A2 Medicina
A2 Medicina
A2 Psicología
K1 Tapentadol
K1 Opioid receptor
K1 Alpha2-adrenoceptor
K1 Locus coeruleus
K1 Desipramine
K1 Morphine
AB Tapentadol is a novel centrally acting drug that combines mu-opioid receptor (MOR) agonism andnoradrenaline reuptake inhibition (NRI), producing analgesic effects in various painful conditions. Weinvestigated the acute effects of tapentadol in the locus coeruleus (LC), a central nucleus regulated by thenoradrenergic and opioid systems that is critical in pain modulation. In single-unit extracellular recordingsof LC neurons from anaesthetized male SpragueeDawley rats, tapentadol clearly inhibited thespontaneous 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 (amu-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 and2.1 mg/kg, respectively). Furthermore, tapentadol inhibited the LC response to mechanical stimulation ofthe hindpaw in a dose-dependent manner. In summary, we demonstrate that acute administration oftapentadol inhibits LC neurons in vivo, mainly due to the activation of alpha2-adrenoceptors. These datasuggest that both the noradrenergic and opioid systems participate in the inhibitory effect of tapentadolon LC neurons, albeit to different extents, which may account for its potent analgesic effect and mildopioidergic side-effects.
SN 0028-3908
YR 2013
FD 2013-01-01T00:00:00Z
LK http://hdl.handle.net/10498/17865
UL http://hdl.handle.net/10498/17865
LA eng
NO This study was supported by grants from Grünenthal GmbH(OT2010/075); “Fondo de Investigación Sanitaria” (PI10/01221 andPI12/00915); CIBERSAM (G18); Junta de Andalucía, Consejería deInnovación, 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
DS Repositorio Institucional de la Universidad de Cádiz
RD 06-nov-2026