ArticlePain2019
Kappa opioid signaling in the central nucleus of the amygdala promotes disinhibition and aversiveness of chronic neuropathic pain.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 98 citations in OpenAlex.
- Kappa opioid receptors in excitatory spinal neurons gate acute pain: evidence from mouse and human.bioRxiv : the preprint server for biology · 2026Article
- Influence of ginger root extract supplementation on the microbiota-gut-brain axis in individuals with sciatica: Study protocol for a double-blind, placebo-controlled randomized trial.Clinical nutrition ESPEN · 2026Article
- Left and Right Hemispheric Lateralization as an Overlooked Variable in Psychiatric Disease: Evidence Across Species.Biological psychiatry · 2026Review
- Psychological vulnerability and opioid medication use disorder risk in chronic pain: the mediating role of affective states and gender differences.Frontiers in public health · 2026Article
- Alcohol use disorder-associated pain: clinical and preclinical evidence.Alcohol (Fayetteville, N.Y.) · 2025Review
- The influence of morphine treatment on the opioid propeptide gene expression in the forebrain of two inbred mouse strains with different sensitivity to opioids.Pharmacological reports : PR · 2025Article
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Diffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies.International journal of molecular sciences · 2025Review
- Unveiling the Applications of Phytoconstituents in Neuropathic Pain.Central nervous system agents in medicinal chemistry · 2025Review
- Effects of a kappa opioid receptor antagonist on delayed postoperative pain recovery in a novel mouse sleep disorder model.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- Early-life pain alters excitability of corticotropin-releasing factor-expressing neurons in the central amygdala and stress-induced hypersensitivity during adolescence.Frontiers in behavioral neuroscience · 2025Article
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Article
- Cortical kappa opioid receptors integrate negative affect and sleep disturbance.Translational psychiatry · 2024Article
- Targeting Prefrontal Cortex Dysfunction in Pain.The Journal of pharmacology and experimental therapeutics · 2024Review
- Article
- Opposing Effects on Descending Control of Nociception by µ and κ Opioid Receptors in the Anterior Cingulate Cortex.Anesthesiology · 2024Article
- Antagonism of kappa opioid receptors accelerates the development of L-DOPA-induced dyskinesia in a preclinical model of moderate dopamine depletion.Brain research · 2023Article
- Buprenorphine for Chronic Pain Management: a Narrative Review.Current pain and headache reports · 2023Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic pain is associated with neuroplastic changes in the amygdala that may promote hyper-responsiveness to mechanical and thermal stimuli (allodynia and hyperalgesia) and/or enhance emotional and affective consequences of pain. Stress promotes dynorphin-mediated signaling at the kappa opioid receptor (KOR) in the amygdala and mechanical hypersensitivity in rodent models of functional pain. Here, we tested the hypothesis that KOR circuits in the central nucleus of the amygdala (CeA) undergo neuroplasticity in chronic neuropathic pain resulting in increased sensory and affective pain responses. After spinal nerve ligation (SNL) injury in rats, pretreatment with a long-acting KOR antagonist, nor-binaltorphimine (nor-BNI), subcutaneously or through microinjection into the right CeA, prevented conditioned place preference (CPP) to intravenous gabapentin, suggesting that nor-BNI eliminated the aversiveness of ongoing pain. By contrast, systemic or intra-CeA administration of nor-BNI had no effect on tactile allodynia in SNL animals. Using whole-cell patch-clamp electrophysiology, we found that nor-BNI decreased synaptically evoked spiking of CeA neurons in brain slices from SNL but not sham rats. This effect was mediated through increased inhibitory postsynaptic currents, suggesting tonic disinhibition of CeA output neurons due to increased KOR activity as a possible mechanism promoting ongoing aversive aspects of neuropathic pain. Interestingly, this mechanism is not involved in SNL-induced mechanical allodynia. Kappa opioid receptor antagonists may therefore represent novel therapies for neuropathic pain by targeting aversive aspects of ongoing pain while preserving protective functions of acute pain.
Indexed as
Identifiers
What OpenQuestion holds
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.