ArticleAnesthesiology2024
Opposing Effects on Descending Control of Nociception by µ and κ Opioid Receptors in the Anterior Cingulate Cortex.
Article in Anesthesiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
- OnabotulinumtoxinA inhibits dysregulation of descending pain modulation following mild traumatic brain injury in mice.The journal of headache and pain · 2025Article
- Pain Perception and Modulation: Fundamental Neurobiology and Recent Advances.The European journal of neuroscience · 2025Review
- Review
- Excitatory Synaptic Transmission Is Differentially Modulated by Opioid Receptors along the Claustrocingulate Pathway.eNeuro · 2025Article
- Targeting PI3K-mTOR signaling in the anterior cingulate cortex improves emotional behavior, and locomotor activity in rats with bone cancer pain.Annals of medicine and surgery (2012) · 2025Article
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Anti-nociceptive properties of cardiopulmonary baroreceptors in patients with chronic back pain.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- Re-wiring of the bonded brain: Gene expression among pair bonded female prairie voles changes as they transition to motherhood.Genes, brain, and behavior · 2024Article
- Age- and Sex-Dependent Effects of Moderate Exercise on Endogenous Pain Inhibition in Rats.Biomedicines · 2024Article
- Article
- Dysregulated neuromodulation in the anterior cingulate cortex in chronic pain.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe efficiency of descending pain modulation, commonly assessed with the conditioned pain modulation procedure, is diminished in patients with chronic pain. The authors hypothesized that the efficiency of pain modulation is controlled by cortical opioid circuits.
methodsThis study evaluated the effects of µ opioid receptor activation in the anterior cingulate cortex on descending control of nociception, a preclinical correlate of conditioned pain modulation, in male Sprague-Dawley rats with spinal nerve ligation-induced chronic pain or in sham-operated controls. Additionally, the study explored the consequences of respective activation or inhibition of κ opioid receptor in the anterior cingulate cortex of naive rats or animals with neuropathic pain. Descending control of nociception was measured as the hind paw withdrawal response to noxious pressure (test stimulus) in the absence or presence of capsaicin injection in the forepaw (conditioning stimulus).
resultsDescending control of nociception was diminished in the ipsilateral, but not contralateral, hind paw of rats with spinal nerve ligation. Bilateral administration of morphine in the anterior cingulate cortex had no effect in shams but restored diminished descending control of nociception without altering hypersensitivity in rats with neuropathic pain. Bilateral anterior cingulate cortex microinjection of κ opioid receptor antagonists, including nor-binaltorphimine and navacaprant, also re-established descending control of nociception in rats with neuropathic pain without altering hypersensitivity and with no effect in shams. Conversely, bilateral injection of a κ opioid receptor agonist, U69,593, in the anterior cingulate cortex of naive rats inhibited descending control of nociception without altering withdrawal thresholds.
conclusionsAnterior cingulate cortex κ opioid receptor activation therefore diminishes descending control of nociception both in naive animals and as an adaptive response to chronic pain, likely by enhancing net descending facilitation. Descending control of nociception can be restored by activation of μ opioid receptors in the anterior cingulate cortex, but also by κ opioid receptor antagonists, providing a nonaddictive alternative to opioid analgesics. Navacaprant is now in advanced clinical trials. EDITOR’S PERSPECTIVE:
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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.