Trial reportThe journal of pain2017
OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients.
Trial report in The journal of pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Perioperative opioids and survival outcomes in resectable head and neck cancer: A systematic review.Cancer medicine · 2023Pooled it
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Molecular Mechanisms Underlying Burn-Injury Induced Pain: From Inflammation to Epigenetics.Military medicine · 2025Review
- Repetitive neonatal pain increases spinal cord DNA methylation of the µ-opioid receptor.Pediatric research · 2025Article
- Review
- Clinical efficacy and regulatory mechanisms of Shi Pi Zeng Ye formula in treating functional constipation comorbid with depression: integrating clinical observation, mass spectrometry, bioinformatics, and molecular docking.Frontiers in pharmacology · 2025Article
- Morphine treatment restricts response to immunotherapy in oral squamous cell carcinoma.Journal for immunotherapy of cancer · 2024Article
- Opioid and Cannabinoid Systems in Pain: Emerging Molecular Mechanisms and Use in Clinical Practice, Health, and Fitness.International journal of molecular sciences · 2024Review
- Sex Differences in Opioid Response Linked toJournal of clinical medicine · 2023Article
- The role of the gut microbiome and microbial metabolism in mediating opioid-induced changes in the epigenome.Frontiers in microbiology · 2023Review
- Advances in Head and Neck Cancer Pain.Journal of dental research · 2022Article
- Identification and characterization of N6-methyladenosine circular RNAs in the spinal cord of morphine-tolerant rats.Frontiers in neuroscience · 2022Article
- Opioid Analgesia and Opioid-Induced Adverse Effects: A Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain.BMC cancer · 2021Article
- The Genomics of Opioid Addiction Longitudinal Study (GOALS): study design for a prospective evaluation of genetic and non-genetic factors for development of and recovery from opioid use disorder.BMC medical genomics · 2021Observational
- Diet, Sports, and Psychological Stress as Modulators of Breast Cancer Risk: Focus onFrontiers in nutrition · 2021Article
- Machine-learned analysis of global and glial/opioid intersection-related DNA methylation in patients with persistent pain after breast cancer surgery.Clinical epigenetics · 2019Article
- Opioid-Induced Tolerance and Hyperalgesia.CNS drugs · 2019Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that chronic cancer pain as well as high-dose opioid use lead to mu-opioid receptor downregulation. In this study we explore downregulation of the mu-opioid receptor gene (OPRM1), as a mechanism for opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in a cohort of 84 cancer patients that high-dose opioid use correlates with OPRM1 hypermethylation in peripheral leukocytes of these patients. We then reverse-translate our clinical findings by creating a mouse cancer pain model; we create opioid tolerance in the mouse cancer model to mimic opioid tolerance in the cancer patients. Using this model we determine the functional significance of OPRM1 methylation on cancer pain and opioid tolerance. We focus on 2 main cells within the cancer microenvironment: the cancer cell and the neuron. We show that targeted re-expression of mu-opioid receptor on cancer cells inhibits mechanical and thermal hypersensitivity, and prevents opioid tolerance, in the mouse model. The resultant analgesia and protection against opioid tolerance are likely due to preservation of mu-opioid receptor expression on the cancer-associated neurons. PERSPECTIVE: We demonstrate that epigenetic regulation of OPRM1 contributes to opioid tolerance in cancer patients, and that targeted gene therapy could treat cancer-induced nociception and opioid tolerance in a mouse cancer model.
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.