ArticleBrain : a journal of neurology2022
Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 82 citations in OpenAlex.
- DNMT1-mediated central amygdala to locus coeruleus circuit contributes to chronic pain-related depression in mice.Acta pharmacologica Sinica · 2026Article
- A new hope: locus coeruleus-norepinephrine system at the nexus of neuropsychiatric symptoms.Molecular psychiatry · 2026Review
- Activation of peripheral muscarinic receptors rescues depressive-like behaviors via gut-brain-axis, involving parasympathetic excitation.Acta pharmacologica Sinica · 2026Article
- Altered locus coeruleus functional connectivity in migraine without aura based on resting-state functional magnetic resonance imaging.Journal of oral & facial pain and headache · 2026Article
- A Central Somatic Transmission Mediates Proprioceptive Facilitation of Muscle Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Norepinephrinergic projection from locus coeruleus to parafascicular nucleus promotes pain and anxiety-like behaviors in mice.JCI insight · 2026Article
- Locus-Coeruleus Norepinephrine Functioning as a Predictor of Childhood Mental Health (LOCUS-MENTAL): Protocol for a Longitudinal Study.JMIR research protocols · 2026Article
- Locus coeruleus modulation of neurophysiological sensory selectivity differs in autism and other mental health conditions.Translational psychiatry · 2026Article
- A brainstem-thalamocortical circuit mediates postoperative pain duration induced by sleep deprivation.Behavioral and brain functions : BBF · 2026Article
- Shared Mechanisms and Integrated Management of Post-Stroke Pain and Depression: A Comprehensive Review.Pain and therapy · 2026Review
- LC-IL but Not LC-PL Circuit Regulates Comorbid Mechanical Hyperalgesia and Anxiety in Male Rats with Chronic Post-Surgical Pain.Journal of pain research · 2026Article
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
- Gonadotropin-releasing hormone alleviates chronic pain-related depression in male mice by rebalancing the anterior cingulate cortex excitatory-inhibitory processes via the protein kinase C/Erb-B2 receptor tyrosine kinase 4 pathway.Brain communications · 2026Article
- Inverse Association of Locus Coeruleus MRI Integrity With Structural Volume and Its Impact on Individual's Inattentiveness.Human brain mapping · 2025Article
- Hippocampal Extracellular Matrix Protein Laminin β1 Regulates Neuropathic Pain and Pain-Related Cognitive Impairment.Neuroscience bulletin · 2025Article
- Circuit-selective pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.Cell reports · 2025Article
- Impact of dynamic changes in pain on cardiovascular disease in Chinese middle and elderly people: results from China Health and Retirement Longitudinal Study (CHARLS).BMC public health · 2025Article
- Spared nerve injury induces long-term and brain region-specific changes in oligodendrocyte density in mice.bioRxiv : the preprint server for biology · 2025Article
- Activation of Locus Coeruleus-Hippocampus Tyrosine Hydroxylase Projection Contributes to the Surgical Incision Pain-Induced Memory Consolidation Enhancement in Mice.CNS neuroscience & therapeutics · 2025Article
- The Locus Coeruleus-Periaqueductal Gray GABAergic Projection Regulates Comorbid Pain and Depression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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