Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons
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- Meritxell Llorca-Torralba
- Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz 11519, Spain
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- Carmen Camarena-Delgado
- Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz 11519, Spain
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- Irene Suárez-Pereira
- Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz 11009, Spain
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- Lidia Bravo
- Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz 11009, Spain
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- Patricia Mariscal
- Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz 11009, Spain
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- Jose Antonio Garcia-Partida
- Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz 11009, Spain
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- Carolina López-Martín
- Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz 11519, Spain
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- Hong Wei
- Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland
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- Antti Pertovaara
- Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland
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- Juan Antonio Mico
- Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz 11009, Spain
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- Esther Berrocoso
- Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cádiz, Cádiz 11519, Spain
説明
<jats:title>Abstract</jats:title><jats:p>There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear.</jats:p><jats:p>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).</jats:p><jats:p>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.</jats:p><jats:p>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.</jats:p>
収録刊行物
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- Brain
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Brain 145 (1), 154-167, 2021-08-09
Oxford University Press (OUP)