ArticleNature medicine2017
Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers.
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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.
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Who cites it
195 citing papers in PubMed, 341 citations in OpenAlex.
- Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- G protein regulatory network shapes magnitude and kinetics of behavioral responses in an engineered opioid receptor model.The Journal of biological chemistry · 2026Article
- Persistent Mu-Opioid Receptor Dysregulation in a Pain-Facilitatory Brain Region Reinstates Hyperalgesia After Resolution of Opioid-Induced Hyperalgesia.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- Adapter protein 2-modulatedActa pharmacologica Sinica · 2026Article
- Diosmetin as an Effective Treatment for Cisplatin-Induced Neuropathic Pain in Mice which does not Cause Hepatic or Renal Biomarker Alterations.Molecular neurobiology · 2026Article
- Topical oleic acid reduces nociception and inflammation in a UVB radiation-induced sunburn model in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Stigmasterol attenuates nociplastic pain and fatigue-like symptoms in a reserpine-induced fibromyalgia model in mice.Inflammopharmacology · 2026Article
- Chronic delivery of buprenorphine during abstinence decreases incubation of heroin seeking and neuronal activation in medial prefrontal cortex and striatum in male and female rats.Psychopharmacology · 2025Article
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Analgesia through FKBP51 inhibition at disease onset confers lasting relief from sensory and emotional chronic pain symptoms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Opposing effects of mu opioid receptors on dopamine D1 and D2 receptor expressing neurons in opioid mediated antinociception.The journal of pain · 2025Article
- Sex-Specific Behavioral Features of Juvenile and Adult Haploinsufficient Scn2aGenes, brain, and behavior · 2025Article
- OPIOID-EXPRESSING B CELLS SILENCE TUMOR-INFILTRATING NOCICEPTOR NEURONS.Research square · 2025Article
- Diosmetin Attenuates Painful Symptoms Caused by Antineoplastics Paclitaxel and Anastrozole in Mice.Molecular neurobiology · 2025Article
- Social Exclusion Amplifies Behavioral Responses to Physical Pain via Insular Neuromodulation.Research square · 2025Article
- Social Exclusion Amplifies Behavioral Responses to Physical Pain via Insular Neuromodulation.bioRxiv : the preprint server for biology · 2025Article
- NETs activate the GAS6-AXL-NLRP3 axis in macrophages to drive morphine tolerance.Cell communication and signaling : CCS · 2025Article
- Mimicking opioid analgesia in cortical pain circuits.bioRxiv : the preprint server for biology · 2025Article
135 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Opioid pain medications have detrimental side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). Tolerance and OIH counteract opioid analgesia and drive dose escalation. The cell types and receptors on which opioids act to initiate these maladaptive processes remain disputed, which has prevented the development of therapies to maximize and sustain opioid analgesic efficacy. We found that μ opioid receptors (MORs) expressed by primary afferent nociceptors initiate tolerance and OIH development. RNA sequencing and histological analysis revealed that MORs are expressed by nociceptors, but not by spinal microglia. Deletion of MORs specifically in nociceptors eliminated morphine tolerance, OIH and pronociceptive synaptic long-term potentiation without altering antinociception. Furthermore, we found that co-administration of methylnaltrexone bromide, a peripherally restricted MOR antagonist, was sufficient to abrogate morphine tolerance and OIH without diminishing antinociception in perioperative and chronic pain models. Collectively, our data support the idea that opioid agonists can be combined with peripheral MOR antagonists to limit analgesic tolerance and OIH.
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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.