ArticleThe Journal of clinical investigation1996
No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 193 citations in OpenAlex.
- Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.Drugs & aging · 2019Pooled it
- Oral or transdermal opioids for osteoarthritis of the knee or hip.The Cochrane database of systematic reviews · 2014Pooled it
- The comparison of intraarticular morphine-bupivacaine and tramadol-bupivacaine in postoperative analgesia after arthroscopic anterior cruciate ligament reconstruction.Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · 2012Trial
- Evidences for antinociceptive effect of 17-α-hydroxyprogesterone caproate in carpal tunnel syndrome.Journal of molecular neuroscience : MN · 2012Trial
- Blockade of intra-articular adrenergic receptors increases analgesic demands for pain relief after knee surgery.Rheumatology international · 2011Trial
- Article
- Peptide-Based Approaches for Pain Relief and Healing in Wounds.International journal of molecular sciences · 2026Review
- Peripheral Opioid Receptors in the Modulation of Inflammatory Pain: a Narrative Review.Maedica · 2025Review
- Interactions Between Endogenous Opioids and the Immune System.Advances in neurobiology · 2024Review
- Neuroimmunology of cancer and associated symptomology.Immunology and cell biology · 2021Review
- Recent Advances in Peripheral Opioid Receptor Therapeutics.Current pain and headache reports · 2021Review
- On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance.Molecules (Basel, Switzerland) · 2020Review
- Opioid Receptors in Immune and Glial Cells-Implications for Pain Control.Frontiers in immunology · 2020Review
- [Pain inhibition by opioids-new concepts].Schmerz (Berlin, Germany) · 2019Review
- [Pain inhibition by opioids-new concepts].Der Anaesthesist · 2019Review
- Effect of ketorolac in intra-articular injection analgesia for postoperative pain in patients undergoing shoulder arthroscopy: a pilot-controlled clinical study.Journal of pain research · 2019Article
- Neutrophil-Mediated Endogenous Analgesia Contributes to Sex Differences in Oral Cancer Pain.Frontiers in integrative neuroscience · 2018Article
- Advances in Achieving Opioid Analgesia Without Side Effects.Frontiers in pharmacology · 2018Review
- Indications for Opioid Antagonists.Current pain and headache reports · 2017Review
- Neuroimmune Interaction in the Regulation of Peripheral Opioid-Mediated Analgesia in Inflammation.Frontiers in immunology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Pain treatment with centrally acting opiates is limited by tolerance. Tolerance is a decreasing effect of a drug with prolonged administration of that drug or of a related (e.g., endogenous) compound acting at the same receptor. This is often associated with a downregulation of receptors. In peripheral inflamed tissue, both locally expressed opioid peptides and morphine can produce powerful analgesia mediated by similar populations of opioid receptors. We hypothesized that the chronic presence of endogenous opioids in inflamed joints might convey downregulation of peripheral opioid receptors and tolerance to the analgesic effects of intraarticular morphine. We assessed these effects after arthroscopic surgery in patients with and without histologically verified synovial cellular infiltration, and we examined synovial opioid peptides and opioid receptors by immunocytochemistry and autoradiography, respectively. We found that, despite an abundance of opioid-containing cells in pronounced synovitis, morphine is at least as effective as in patients without such cellular infiltrations, and there is no major downregulation of peripheral opioid receptors. Thus, opioids expressed in inflamed tissue do not produce tolerance to peripheral morphine analgesia. Tolerance may be less pronounced for peripherally than for centrally acting opioids, which provides a promising perspective for the treatment of chronic pain in arthritis and other inflammatory conditions.
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.