RT journal article
T1 Opioid Activity in the Locus Coeruleus Is Modulated by Chronic Neuropathic Pain
A1 Llorca Torralba, Meritxell
A1 Pilar Cuéllar, Fuencisla
A1 Bravo García, Lidia
A1 Bruzos-Cidon, Cristina
A1 Torrecilla, María
A1 Micó Segura, Juan Antonio
A1 Ugedo, Luisa
A1 Garro-Martínez, Emilio
A1 Berrocoso Domínguez, Esther María
A2 Neurociencias
A2 Psicología
K1 Locus coeruleus . Neuropathic pain . Mu opioid receptor . Morphine
AB Pain affects both sensory and emotional aversive responses, often provoking depression and anxiety-related conditions when it becomes chronic. As the opioid receptors in the locus coeruleus (LC) have been implicated in pain, stress responses, and opioid drug effects, we explored the modifications to LC opioid neurotransmission in a chronic constriction injury (CCI) model of shortand long-term neuropathic pain (7 and 30 days after nerve injury). No significant changes were found after short-term CCI, yetafter 30 days, CCI provoked an up-regulation of cAMP (cyclic 5′-adenosine monophosphate), pCREB (phosphorylated cAMP response element binding protein), protein kinase A, tyrosine hydroxylase, and electrical activity in the LC, as well as enhanced c-Fos expression. Acute mu opioid receptor desensitization was more intense in these animals, measured as the decline of the peak current caused by [Met5]-enkephalin and the reduction of forskolin-stimulated cAMP produced in response to DAMGO.Sustained morphine treatment did not markedly modify certain LC parameters in CCI-30d animals, such as [Met5]-enkephalininduced potassium outward currents or burst activity and c-Fos rebound after naloxone precipitation, which may limit the development of some typical opioid drug-related adaptations. However, other phenomena were impaired by long-term CCI, including the reduction in forskolin-stimulated cAMP accumulation by DAMGO after naloxone precipitation in morphinedependent animals. Overall, this study suggests that long-term CCI leads to changes at the LC level that may contribute to the anxiodepressive phenotype that develops in these animals. Furthermore, opioid drugs produce complex adaptations in the LC in this model of chronic neuropathic pain.
PB SPRINGER
SN 1559-1182
YR 2018
FD 2018-09-20
LK http://hdl.handle.net/10498/30268
UL http://hdl.handle.net/10498/30268
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-may-2026