RT Journal Article
T1 Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons
A1 Llorca-Torralba, Meritxell
A1 Camarena-Delgado, Carmen
A1 Suarez-Pereira, Irene
A1 Bravo, Lidia
A1 Mariscal, Patricia
A1 Antonio Garcia-Partida, Jose
A1 Lopez-Martin, Carolina
A1 Wei, Hong
A1 Pertovaara, Antti
A1 Mico, Juan Antonio
A1 Berrocoso, Esther
K1 locus coeruleus
K1 depression
K1 neuropathic pain
K1 anterior cingulate cortex
K1 spinal cord
K1 Chronic constriction injury
K1 Anterior cingulate cortex
K1 Peripheral-nerve injury
K1 Neuropathic pain
K1 Growth-factor
K1 Rat model
K1 Stress
K1 Brain
K1 Disorders
K1 Behaviors
AB There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi -> spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.
PB Oxford univ press
SN 0006-8950
YR 2022
FD 2022-01-12
LK https://hdl.handle.net/10668/25202
UL https://hdl.handle.net/10668/25202
LA en
DS RISalud
RD Apr 7, 2025