ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Microglia disrupt mesolimbic reward circuitry in chronic pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- A protocol for the Teen Bugs study: An integrative, multi-omics approach to understanding the role of the gut microbiome and mesocorticolimbic system in adolescent mental health following early adverse caregiving.Brain, behavior, & immunity - health · 2026Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Serum Zonulin Levels in Patients with Heroin Addiction.Sisli Etfal Hastanesi tip bulteni · 2026Article
- The role of nucleus accumbens dopamine signaling in the development of morphine tolerance in neuropathic pain.The Korean journal of pain · 2026Article
- Dynamic changes in chloride homeostasis coordinate midbrain inhibitory network activity during reward learning.Nature communications · 2025Article
- Dysregulation of Hedonic Processing in Chronic Pain: Insights from Preclinical Data.Brain sciences · 2025Review
- Development and validation of a risk prediction model for co-existing depression in middle-aged and older adults with low back pain.European journal of medical research · 2025Article
- Reduced SK channel control of mesolimbic dopamine neuron firing drives reward seeking adaptations in chronic pain.bioRxiv : the preprint server for biology · 2025Article
- Opposing effects of mu opioid receptors on dopamine D1 and D2 receptor expressing neurons in opioid mediated antinociception.The journal of pain · 2025Article
- Chronic pain selectively reduces the motivation to work for remifentanil but not food reward.Pain · 2025Article
- Estradiol protects against pain-facilitated fentanyl use via suppression of opioid-evoked dopamine activity in males.Neuron · 2025Article
- BDNF Signaling and Pain Modulation.Cells · 2025Review
- Chronic Pain and Comorbid Emotional Disorders: Neural Circuitry and Neuroimmunity Pathways.International journal of molecular sciences · 2025Review
- Modulation of comorbid depression of neuropathic pain by dopamine input from VTA to the ventral hippocampus.Theranostics · 2025Article
- A ketogenic diet regulates microglial activation to treat drug addiction.Frontiers in pharmacology · 2025Review
- Interactions of pain and opioids on conditioned place preference in rodents.Psychopharmacology · 2025Review
- JMJD3 deficiency disturbs dopamine biosynthesis in midbrain and aggravates chronic inflammatory pain.Acta neuropathologica communications · 2024Article
- Midbrain KCC2 downregulation: Implications for stress-related and substance use behaviors.Current opinion in neurobiology · 2024Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic pain attenuates midbrain dopamine (DA) transmission, as evidenced by a decrease in opioid-evoked DA release in the ventral striatum, suggesting that the occurrence of chronic pain impairs reward-related behaviors. However, mechanisms by which pain modifies DA transmission remain elusive. Using in vivo microdialysis and microinjection of drugs into the mesolimbic DA system, we demonstrate in mice and rats that microglial activation in the VTA compromises not only opioid-evoked release of DA, but also other DA-stimulating drugs, such as cocaine. Our data show that loss of stimulated extracellular DA is due to impaired chloride homeostasis in midbrain GABAergic interneurons. Treatment with minocycline or interfering with BDNF signaling restored chloride transport within these neurons and recovered DA-dependent reward behavior. Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic signaling and reward behavior. These results have broad implications that are not restricted to the problem of pain, but are also relevant to affective disorders associated with disruption of reward circuitry. Because chronic pain causes glial activation in areas of the CNS important for mood and affect, our findings may translate to other disorders, including anxiety and depression, that demonstrate high comorbidity with chronic pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.