Publication: Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons.
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Identifiers
Date
2022-01-12
Authors
Llorca-Torralba, Meritxell
Camarena-Delgado, Carmen
Suarez-Pereira, Irene
Bravo, Lidia
Mariscal, Patricia
Garcia-Partida, Jose Antonio
Lopez-Martin, Carolina
Wei, Hong
Pertovaara, Antti
Mico, Juan Antonio
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University Press
Abstract
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.
Description
MeSH Terms
Animals
Comorbidity
Depression
Humans
Locus coeruleus
Neuralgia
Neurons
Rats
Comorbidity
Depression
Humans
Locus coeruleus
Neuralgia
Neurons
Rats
DeCS Terms
Animals
Comorbidity
Depression
Humans
Neuronas
Rats
Comorbidity
Depression
Humans
Neuronas
Rats
CIE Terms
Keywords
Anterior cingulate cortex, Depression, Locus coeruleus, Neuropathic pain, Spinal cord
Citation
Llorca-Torralba M, Camarena-Delgado C, Suárez-Pereira I, Bravo L, Mariscal P, Garcia-Partida JA, et al. Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons. Brain. 2022 Mar 29;145(1):154-167