ArticleAnnals of neurology2010
How to design an opioid drug that causes reduced tolerance and dependence.
Article in Annals of neurology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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
31 citing papers in PubMed, 65 citations in OpenAlex.
- Virtual reality analgesia for burn joint flexibility: A randomized controlled trial.Rehabilitation psychology · 2018Trial
- Virtual reality pain control during burn wound debridement of combat-related burn injuries using robot-like arm mounted VR goggles.The Journal of trauma · 2011Trial
- Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Persistent Transcriptome Alterations in Zebrafish Embryos After Discontinued Opioid Exposure.International journal of molecular sciences · 2025Article
- Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives.Molecular and cellular biochemistry · 2024Review
- Pharmacological and genetic manipulations at the µ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Opioid Analgesia and Opioid-Induced Adverse Effects: A Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Review
- Article
- Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain.Neural regeneration research · 2018Article
- The Effect of Massage on Anticipatory Anxiety and Procedural Pain in Patients with Burn Injury.World journal of plastic surgery · 2017Article
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Endocytosis as a biological response in receptor pharmacology: evaluation by fluorescence microscopy.PloS one · 2015Article
- Opioid receptor trafficking and interaction in nociceptors.British journal of pharmacology · 2015Review
- Association of OPRD1 polymorphisms with heroin dependence in a large case-control series.Addiction biology · 2014Article
- The prevalence, maintenance, and relevance of G protein-coupled receptor oligomerization.Molecular pharmacology · 2013Review
- A new approach for aggregation of Paramecium caudatum by nitric oxide.Iranian journal of microbiology · 2013Article
- Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.Pharmacological reviews · 2013Review
- Ligand-directed signalling within the opioid receptor family.British journal of pharmacology · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mu opioid receptor (MOR) agonists such as morphine are extremely effective treatments for acute pain. In the setting of chronic pain, however, their long-term utility is limited by the development of tolerance and physical dependence. Drug companies have tried to overcome these problems by simply "dialing up" signal transduction at the receptor, designing more potent and efficacious agonists and more long-lasting formulations. Neither of these strategies has proven to be successful, however, because the net amount of signal transduction, particularly over extended periods of drug use, is a product of much more than the pharmacokinetic properties of potency, efficacy, half-life, and bioavailability, the mainstays of traditional pharmaceutical screening. Both the quantity and quality of signal transduction are influenced by many regulated processes, including receptor desensitization, trafficking, and oligomerization. Importantly, the efficiency with which an agonist first stimulates signal transduction is not necessarily related to the efficiency with which it stimulates these other processes. Here we describe recent findings that suggest MOR agonists with diminished propensity to cause tolerance and dependence can be identified by screening drugs for the ability to induce MOR desensitization, endocytosis, and recycling. We also discuss preliminary evidence that heteromers of the delta opioid receptor and the MOR are pronociceptive, and that drugs that spare such heteromers may also induce reduced tolerance.
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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.