ArticleScience (New York, N.Y.)2013
Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence.
Article in Science (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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.
Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperalgesia During a Burn Injury. A Randomized, Placebo-controlled, Double-blind Crossover Study
Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperal-gesia in Patients Following Recovery From Impacted Mandibular Third Molar Extraction. A Randomized, Placebo-controlled, Double-blind Crossover Study.
Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 231 citations in OpenAlex.
- Endogenous opioid antagonism in physiological experimental pain models: a systematic review.PloS one · 2015Pooled it
- Trial
- Trial
- Trial
- Endogenous opioid inhibition of chronic low-back pain influences degree of back pain relief after morphine administration.Regional anesthesia and pain medicineTrial
- BLA kappa opioid receptor inputs to the BNST mediate social stress-induced increases in alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The Intraplantar CFA Inflammatory Pain Model Incompletely Captures Pain Comorbidities Across Sexes.Journal of neuroscience research · 2026Article
- Top-down control of the descending pain modulatory system drives multimodal placebo analgesia.Neuron · 2026Article
- Recombinant dimeric PICK1 peptide inhibitors for long-term relief of chronic pain by AAV therapeutics.Cell reports. Medicine · 2026Article
- Central amygdalar PKCδ neurons mediate fentanyl withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Persistent Mu-Opioid Receptor Dysregulation in a Pain-Facilitatory Brain Region Reinstates Hyperalgesia After Resolution of Opioid-Induced Hyperalgesia.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Bidirectional Roles of TRPV1 in a Latent Sensitization Model of Myofascial Low Back Pain.European journal of pain (London, England) · 2026Article
- Reserpine-induced fibromyalgia model in female rats is a long-lasting painful condition masked by antinociceptive endogenous opioids.Frontiers in pharmacology · 2026Article
- Synergistic effects of levo-tetrahydropalmatine and low-dose naltrexone on nicotine conditioned place preference in mice: a dual-target strategy based on dopamine and opioid systems.Frontiers in pharmacology · 2026Article
- The relationship between neighborhood disadvantage and markers of chronic pain risk: Findings from the Oklahoma Study of Native American Pain Risk (OK-SNAP).The journal of pain · 2025Article
- Prior adolescent oxycodone exposure enhances pain sensitivity following chronic intermittent ethanol in adult female mice.Physiology & behavior · 2025Article
- The pharmacotherapeutic potential of neuropeptide Y for chronic pain.Journal of internal medicine · 2025Review
- Long-lasting and fast methylglyoxal-scavenging peptide CycK(Myr)RPain reports · 2025Article
- Review
- Distinctive biochemical properties of the μ-opioid receptor-corticotropin- releasing factor CRFPharmacological research · 2025Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced μ-opioid receptor (MOR) constitutive activity (MOR(CA)) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3',5'-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MOR(CA) initiates both analgesic signaling and a compensatory opponent process that generates endogenous opioid dependence. Tonic MOR(CA) suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic 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.