ArticlePain2018
Mu-opioid receptors in nociceptive afferents produce a sustained suppression of hyperalgesia in chronic pain.
Article in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 27 citations in OpenAlex.
- The Intraplantar CFA Inflammatory Pain Model Incompletely Captures Pain Comorbidities Across Sexes.Journal of neuroscience research · 2026Article
- Reserpine-induced fibromyalgia model in female rats is a long-lasting painful condition masked by antinociceptive endogenous opioids.Frontiers in pharmacology · 2026Article
- Sex differences in the transition to chronic pain.The Journal of clinical investigation · 2025Review
- Assessing the impact of common pain medications on gut microbiota composition and metabolites: insights from a Mendelian randomization study.Journal of medical microbiology · 2025Article
- Article
- Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.Brain, behavior, and immunity · 2025Article
- Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury.bioRxiv : the preprint server for biology · 2024Article
- Opioids and Ocular Surface Pathology: A Literature Review of New Treatments Horizons.Journal of clinical medicine · 2022Review
- Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain.Journal of neuroscience research · 2022Article
- GRK2 Dictates a Functional Switch of the Peripheral Mu-Opioid Receptor.ACS chemical neuroscience · 2020Article
- A Src family kinase maintains latent sensitization in rats, a model of inflammatory and neuropathic pain.Brain research · 2020Article
- Role of peripheral sensory neuron mu-opioid receptors in nociceptive, inflammatory, and neuropathic pain.Regional anesthesia and pain medicine · 2020Article
- Neurokinin 1 receptor activation in the rat spinal cord maintains latent sensitization, a model of inflammatory and neuropathic chronic pain.Neuropharmacology · 2020Article
- Protagonist Role of Opioidergic System on Post-Traumatic Stress Disorder and Associated Pain.Psychiatry investigation · 2020Article
- Mu and delta opioid receptors play opposite nociceptive and behavioural roles on nerve-injured mice.British journal of pharmacology · 2020Article
- Recent advances toward understanding the mysteries of the acute to chronic pain transition.Current opinion in physiology · 2019Article
- Article
- Alleviation of paclitaxel-induced mechanical hypersensitivity and hyperalgesic priming with AMPK activators in male and female mice.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The latent sensitization model of chronic pain reveals that recovery from some types of long-term hyperalgesia is an altered state in which nociceptive sensitization persists but is suppressed by the ongoing activity of analgesic receptors such as μ-opioid receptors (MORs). To determine whether these MORs are the ones present in nociceptive afferents, we bred mice expressing Cre-recombinase under the Nav1.8 channel promoter (Nav1.8cre) with MOR-floxed mice (flMOR). These Nav1.8cre/flMOR mice had reduced MOR expression in primary afferents, as revealed by quantitative PCR, in situ hybridization, and immunofluorescence colocalization with the neuropeptide calcitonin gene-related peptide. We then studied the recovery from chronic pain of these mice and their flMOR littermates. When Nav1.8cre/flMOR mice were injected in the paw with complete Freund adjuvant they developed mechanical hyperalgesia that persisted for more than 2 months, whereas the responses of flMOR mice returned to baseline after 3 weeks. We then used the inverse agonist naltrexone to assess ongoing MOR activity. Naltrexone produced a robust reinstatement of hyperalgesia in control flMOR mice, but produced no effect in the Nav1.8/flMOR males and a weak reinstatement of hyperalgesia in Nav1.8/flMOR females. Naltrexone also reinstated swelling of the hind paw in flMOR mice and female Nav1.8cre/flMOR mice, but not male Nav1.8cre/flMOR mice. The MOR agonist DAMGO inhibited substance P release in flMOR mice but not Nav1.8cre/flMOR mice, demonstrating a loss of MOR function at the central terminals of primary afferents. We conclude that MORs in nociceptive afferents mediate an ongoing suppression of hyperalgesia to produce remission from chronic pain.
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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.