RT journal article
T1 Nerve injury induces transient locus coeruleus activation over time: role of the locus coeruleus–dorsal reticular nucleus pathway
A1 Camarena Delgado, María del Carmen
A1 Llorca Torralba, Meritxell
A1 Suárez-Pereira, Irene
A1 Bravo García, Lidia
A1 López Martín, Carolina
A1 García Partida, José Antonio
A1 Micó Segura, Juan Antonio
A1 Berrocoso Domínguez, Esther María
A2 Neurociencias
A2 Psicología
K1 Locus coeruleus
K1 Neuropathic pain
K1 Dorsal reticular nucleus
K1 Depression
AB The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. Using the chronic constriction injury of the sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats, we identified time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion, hypothesizing that the LC→dorsal reticular nucleus (DRt) pathway is involved in the pathological nociception associated with chronic pain. LCipsiinactivation with lidocaine increased cold allodynia 2 days after nerve injury but not later. However, similar blockade of LCcontrareduced cold allodynia 7 and 30 days after inducing neuropathy but not earlier. Furthermore, lidocaine blockade of the LCipsior LCcontrareversed pain-induced depression 30 days after neuropathy. Long-Term pain enhances phosphorylated cAMP-response element binding protein expression in the DRtcontrabut not in the DRtipsi. Moreover, inactivation of the LCcontra→DRtcontrapathway using dual viral-mediated gene transfer of designer receptor exclusively activated by designer drugs produced consistent analgesia in evoked and spontaneous pain 30 days postinjury. This analgesia was similar to that produced by spinal activation of α2-Adrenoreceptors. Furthermore, chemogenetic inactivation of the LCcontra→DRtcontrapathway induced depressive-like behaviour in naïve animals, but it did not modify long-Term pain-induced depression. Overall, nerve damage activates the LCipsi, which temporally dampens the neuropathic phenotype. However, the ensuing activation of a LCcontra→DRtcontrafacilitatory pain projection contributes to chronic pain, whereas global bilateral LC activation contributes to associated depressive-like phenotype.
PB LIPPINCOTT WILLIAMS & WILKINS
SN 1872-6623
YR 2022
FD 2022-05
LK http://hdl.handle.net/10498/30267
UL http://hdl.handle.net/10498/30267
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026