ReviewFrontiers in systems neuroscience2022
Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward.
Review in Frontiers in systems neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 25 citations in OpenAlex.
- EphB1 Receptor Blockade Augments Morphine Antinociception via Inhibiting GRK2-Mediated µ-Opioid Receptor Internalization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GEM-GPT Enables Personalized Cell Type-Resolved Therapeutic Design for Systems Pharmacology.bioRxiv : the preprint server for biology · 2026Article
- Article
- Dermorphin blocks apneic response to intravenous bolus injection of fentanyl.Toxicology and applied pharmacology · 2026Article
- Review
- Relationships between Musculoskeletal Disorders, Sleep Impairment, and Cardiorespiratory Fitness among Adolescents Aged 15-19 Years in Douala, Cameroon: A Cross-sectional Study.International journal of school health · 2026Article
- μ Opioid Modulation of Sensorimotor Functional Connectivity in Autism: Insights From a Pharmacological Neuroimaging Investigation Using Tianeptine.Biological psychiatry global open science · 2026Article
- Pharmacological Mechanisms and Clinical Applications of Oxycodone in Cancer Pain Management: A Narrative Review.Drug design, development and therapy · 2026Review
- Unmasking a neurotoxic duo: a comprehensive overview of fentanyl-xylazine crosstalk in kinase pathways.Frontiers in cellular neuroscience · 2026Article
- Pain Signaling by GPCRs and RTKs.Trends in pharmacological sciences · 2025Review
- Methadone and Buprenorphine as Medication for Addiction Treatment Diversely Affect Inflammation and Craving Depending on Their Doses.Pharmacy (Basel, Switzerland) · 2025Article
- A Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System.Biomedicines · 2025Review
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- FLT3 signaling inhibition abrogates opioid tolerance and hyperalgesia while preserving analgesia.Nature communications · 2024Article
- Single molecule tracking based drug screening.Nature communications · 2024Article
- Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.Nature communications · 2024Article
- Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.Molecular psychiatry · 2023Article
- Involvement of the Opioid Peptide Family in Cancer Progression.Biomedicines · 2023Review
- Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain.Pharmaceutics · 2023Review
- Peripheral mechanisms of peripheral neuropathic pain.Frontiers in molecular neuroscience · 2023Review
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the prevalence of opioid misuse, opioids remain the frontline treatment regimen for severe pain. However, opioid safety is hampered by side-effects such as analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, or reward. These side effects promote development of opioid use disorders and ultimately cause overdose deaths due to opioid-induced respiratory depression. The intertwined nature of signaling via μ-opioid receptors (MOR), the primary target of prescription opioids, with signaling pathways responsible for opioid side-effects presents important challenges. Therefore, a critical objective is to uncouple cellular and molecular mechanisms that selectively modulate analgesia from those that mediate side-effects. One such mechanism could be the transactivation of receptor tyrosine kinases (RTKs) via MOR. Notably, MOR-mediated side-effects can be uncoupled from analgesia signaling via targeting RTK family receptors, highlighting physiological relevance of MOR-RTKs crosstalk. This review focuses on the current state of knowledge surrounding the basic pharmacology of RTKs and bidirectional regulation of MOR signaling, as well as how MOR-RTK signaling may modulate undesirable effects of chronic opioid use, including opioid analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, and reward. Further research is needed to better understand RTK-MOR transactivation signaling pathways, and to determine if RTKs are a plausible therapeutic target for mitigating opioid side effects.
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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 Socratic graph.