TY  - JOUR
PY  - 2021//
TI  - Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons
JO  - Brain: a journal of neurology
A1  - Llorca-Torralba, Meritxell
A1  - Camarena-Delgado, Carmen
A1  - Suárez-Pereira, Irene
A1  - Bravo, Lidia
A1  - Mariscal, Patricia
A1  - Garcia-Partida, Jose Antonio
A1  - López-Martín, Carolina
A1  - Wei, Hong
A1  - Pertovaara, Antti
A1  - Mico, Juan Antonio
A1  - Berrocoso, Esther
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - 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 (LC) neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) 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 behavior 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 LC-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 LC-rostral anterior cingulate cortex (rACC) pathway or the intra-rACC antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic LC to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific LC modules promotes early restorative-analgesia, as well as late depressive-like behavior in chronic pain and depression comorbidity.<p />  <p>Language: en</p>
LA  - en
SN  - 0006-8950
UR  - http://dx.doi.org/10.1093/brain/awab239
ID  - ref1
ER  -