ArticleThe journal of pain2012
Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat.
Article in The journal of pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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
16 citing papers in PubMed, 29 citations in OpenAlex.
- Repeated Tetrahydrocannabinol Injections Induce Tolerance but Do Not Disrupt Ongoing Behaviour Upon Withdrawal in Male and Female Rats With Inflammatory Pain.European journal of pain (London, England) · 2026Article
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Morphine and Fentanyl Repeated Administration Induces Different Levels of NLRP3-Dependent Pyroptosis in the Dorsal Raphe Nucleus of Male Rats via Cell-Specific Activation of TLR4 and Opioid Receptors.Cellular and molecular neurobiology · 2022Article
- Endogenous opioid systems alterations in pain and opioid use disorder.Frontiers in systems neuroscience · 2022Review
- Lack of Antinociceptive Cross-Tolerance With Co-Administration of Morphine and Fentanyl Into the Periaqueductal Gray of Male Sprague-Dawley Rats.The journal of pain · 2019Article
- Inflammatory mediators of opioid tolerance: Implications for dependency and addiction.Peptides · 2019Review
- Enhanced antinociception with repeated microinjections of apomorphine into the periaqueductal gray of male and female rats.Behavioural pharmacology · 2018Article
- Entanglement between thermoregulation and nociception in the rat: the case of morphine.Journal of neurophysiology · 2016Article
- Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat.The European journal of neuroscience · 2016Article
- Sex Differences in GABAA Signaling in the Periaqueductal Gray Induced by Persistent Inflammation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Ligand-biased activation of extracellular signal-regulated kinase 1/2 leads to differences in opioid induced antinociception and tolerance.Behavioural brain research · 2016Article
- Change in functional selectivity of morphine with the development of antinociceptive tolerance.British journal of pharmacology · 2015Article
- Contribution of adenylyl cyclase modulation of pre- and postsynaptic GABA neurotransmission to morphine antinociception and tolerance.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Functionally selective signaling for morphine and fentanyl antinociception and tolerance mediated by the rat periaqueductal gray.PloS one · 2014Article
- Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat.The journal of pain · 2013Article
- Blockade of Toll-like receptor 4 attenuates morphine tolerance and facilitates the pain relieving properties of morphine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledSystemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. The magnitude of tolerance to morphine was comparable following 1, 4, or 8 pretreatments. Tolerance to fentanyl also was evident following 4 or 8 microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the 1 exception of no tolerance to acute administration of fentanyl. PERSPECTIVE: These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly and is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments.
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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.