ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Endogenous opioid activity in the anterior cingulate cortex is required for relief of 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 101 papers.
What it found
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The trial behind it
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Who cites it
101 citing papers in PubMed, 189 citations in OpenAlex.
- Trial
- Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study.NeuroImage. Clinical · 2018Trial
- Dynamic coupling of emotion and pain: from perception to affective response.The Korean journal of pain · 2026Review
- Article
- Exercise intervention for rumination: from neural mechanisms to clinical applications.Frontiers in psychology · 2026Review
- Article
- Delta Opioid Receptors on Parvalbumin Neurons are Necessary for the Convulsant and Anxiolytic Effects of the Delta Agonist SNC80.bioRxiv : the preprint server for biology · 2025Article
- Combining mindfulness intervention and open-label placebo treatment for chronic pain: a protocol for a feasibility study.Pilot and feasibility studies · 2025Article
- Reflecting on Cancer Pain as Constant Acute Pain, not Chronic Pain. 'Known Knowns, Known Unknowns, Unknown Unknowns'.Current oncology reports · 2025Review
- Mimicking opioid analgesia in cortical pain circuits.bioRxiv : the preprint server for biology · 2025Article
- Intersect between brain mechanisms of conditioned threat, active avoidance, and reward.Communications psychology · 2025Review
- Pregnancy ameliorates neuropathic pain through suppression of microglia and upregulation of the δ-opioid receptor in the anterior cingulate cortex in late-pregnant mice.Journal of anesthesia · 2024Article
- Chronic morphine treatment induces sex- and synapse-specific cellular tolerance on thalamo-cortical mu opioid receptor signaling.Journal of neurophysiology · 2024Article
- The 'in's and out's' of descending pain modulation from the rostral ventromedial medulla.Trends in neurosciences · 2024Review
- Targeting Prefrontal Cortex Dysfunction in Pain.The Journal of pharmacology and experimental therapeutics · 2024Review
- Opposing Effects on Descending Control of Nociception by µ and κ Opioid Receptors in the Anterior Cingulate Cortex.Anesthesiology · 2024Article
- Chronic Morphine Induces Adaptations in Opioid Receptor Signaling in a Thalamostriatal Circuit That Are Location Dependent, Sex Specific, and Regulated by μ-Opioid Receptor Phosphorylation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Enhancing chronic low back pain management: an initial neuroimaging study of a mobile interoceptive attention training.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- Cell-type specific molecular architecture for mu opioid receptor function in pain and addiction circuits.Neuropharmacology · 2023Review
- The Endogenous Opioid Met-Enkephalin Modulates Thalamo-Cortical Excitation Inhibition Balance in a Medial Thalamus-Anterior Cingulate Cortex Circuit.bioRxiv : the preprint server for biology · 2023Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Pain is aversive, and its relief elicits reward mediated by dopaminergic signaling in the nucleus accumbens (NAc), a part of the mesolimbic reward motivation pathway. How the reward pathway is engaged by pain-relieving treatments is not known. Endogenous opioid signaling in the anterior cingulate cortex (ACC), an area encoding pain aversiveness, contributes to pain modulation. We examined whether endogenous ACC opioid neurotransmission is required for relief of pain and subsequent downstream activation of NAc dopamine signaling. Conditioned place preference (CPP) and in vivo microdialysis were used to assess negative reinforcement and NAc dopaminergic transmission. In rats with postsurgical or neuropathic pain, blockade of opioid signaling in the rostral ACC (rACC) inhibited CPP and NAc dopamine release resulting from non-opioid pain-relieving treatments, including peripheral nerve block or spinal clonidine, an α2-adrenergic agonist. Conversely, pharmacological activation of rACC opioid receptors of injured, but not pain-free, animals was sufficient to stimulate dopamine release in the NAc and produce CPP. In neuropathic, but not sham-operated, rats, systemic doses of morphine that did not affect withdrawal thresholds elicited CPP and NAc dopamine release, effects that were prevented by blockade of ACC opioid receptors. The data provide a neural explanation for the preferential effects of opioids on pain affect and demonstrate that engagement of NAc dopaminergic transmission by non-opioid pain-relieving treatments depends on upstream ACC opioid circuits. Endogenous opioid signaling in the ACC appears to be both necessary and sufficient for relief of pain aversiveness.
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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.