ArticlePain2018
Analgesic effects of a novel pH-dependent μ-opioid receptor agonist in models of neuropathic and abdominal 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 35 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
35 citing papers in PubMed, 62 citations in OpenAlex.
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- Emerging therapeutic approaches for treating abdominal pain.Journal of the Canadian Association of Gastroenterology · 2025Review
- Peripheral Opioid Receptors in the Modulation of Inflammatory Pain: a Narrative Review.Maedica · 2025Review
- Biased Opioid Receptor Agonists: Balancing Analgesic Efficacy and Side-Effect Profiles.International journal of molecular sciences · 2025Review
- A pH-sensitive opioid does not exhibit analgesic tolerance in a mouse model of colonic inflammation.British journal of pharmacology · 2025Article
- Effects of pH on opioid receptor activation and implications for drug design.Biophysical journal · 2024Review
- Assessment of the antinociceptive, respiratory-depressant, and reinforcing effects of the low pKNeuropharmacology · 2024Article
- Signaling Modulation Mediated by Ligand Water Interactions with the Sodium Site at μOR.ACS central science · 2024Article
- Targeting sensory neuron GPCRs for peripheral neuropathic pain.Trends in pharmacological sciences · 2023Review
- Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design.Scientific reports · 2023Article
- Modulation of G-protein activation, calcium currents and opioid receptor phosphorylation by the pH-dependent antinociceptive agonist NFEPP.Frontiers in molecular neuroscience · 2023Article
- Amelioration of injury-induced tissue acidosis by a nonsteroidal analgesic attenuates antinociceptive effects of the pH-dependent opioid agonist NFEPP.Scientific reports · 2022Article
- Article
- Delta opioid receptors on nociceptive sensory neurons mediate peripheral endogenous analgesia in colitis.Journal of neuroinflammation · 2022Article
- Opioid Receptors and Protonation-Coupled Binding of Opioid Drugs.International journal of molecular sciences · 2021Review
- Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice.International journal of molecular sciences · 2021Article
- Recent Advances in Peripheral Opioid Receptor Therapeutics.Current pain and headache reports · 2021Review
- Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Effect of multimodal analgesia on gynecological cancer patients after radical resection.American journal of translational research · 2021Article
- Optimizing Perioperative Use of Opioids: A Multimodal Approach.Current anesthesiology reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), a newly designed μ-opioid receptor (MOR) agonist with a low pKa, has been shown to produce injury-restricted analgesia in models of inflammatory and postoperative pain, without exhibiting typical opioid side effects. Here, we investigated MOR binding of NFEPP in brain and dorsal root ganglia, pH in injured tissues, and the analgesic efficacy of NFEPP compared with fentanyl in a chronic constriction injury model of neuropathic pain, and in the acetic acid-induced abdominal writhing assay in rats. Binding experiments revealed significantly lower affinity of NFEPP compared with fentanyl at pH 7.4. In vivo, pH significantly dropped both at injured nerves after chronic constriction injury and in the abdominal cavity after acetic acid administration. Intravenous NFEPP as well as fentanyl dose-dependently diminished neuropathy-induced mechanical and heat hypersensitivity, and acetic acid-induced abdominal constrictions. In both models, NFEPP-induced analgesia was fully reversed by naloxone methiodide, a peripherally restricted opioid receptor antagonist, injected at the nerve injury site or into the abdominal cavity. Our results indicate that NFEPP exerts peripheral opioid receptor-mediated analgesia exclusively in damaged tissue in models of neuropathic and abdominal 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.