ArticleThe journal of pain2019
Lack of Antinociceptive Cross-Tolerance With Co-Administration of Morphine and Fentanyl Into the Periaqueductal Gray of Male Sprague-Dawley Rats.
Article in The journal of pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Atypical Fentanyl Transdermal Patch Consumption and Fatalities: Case Report and Literature Review.Toxics · 2022Article
- Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse.Neuroscience bulletin · 2022Review
- Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain.BMC cancer · 2021Article
- Use of home cage wheel running to assess the behavioural effects of administering a mu/delta opioid receptor heterodimer antagonist for spontaneous morphine withdrawal in the rat.Behavioural brain research · 2021Article
- Melatonin alleviates morphine analgesic tolerance in mice by decreasing NLRP3 inflammasome activation.Redox biology · 2020Article
- Adrenomedullin: an important participant in neurological diseases.Neural regeneration research · 2020Review
- Fentanyl depression of respiration: Comparison with heroin and morphine.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Tolerance to the antinociceptive effect of mu-opioid receptor agonists, such as morphine and fentanyl, greatly limits their effectiveness for long-term use to treat pain. Clinical studies have shown that combination therapy and opioid rotation can be used to enhance opioid-induced antinociception once tolerance has developed. The mechanism and brain regions involved in these processes are unknown. The purpose of this study was to evaluate the contribution of the ventrolateral periaqueductal gray (vlPAG) to antinociceptive tolerance and cross-tolerance between administration and co-administration of morphine and fentanyl. Tolerance was induced by pretreating rats with morphine or fentanyl or low-dose combination of morphine and fentanyl into the vlPAG followed by an assessment of the cross-tolerance to the other opioid. In addition, tolerance to the combined treatment was assessed. Cross-tolerance did not develop between repeated vlPAG microinjections of morphine and fentanyl. Likewise, there was no evidence of cross-tolerance from morphine or fentanyl to the co-administration of morphine and fentanyl. Co-administration did not cause cross-tolerance to fentanyl. Cross-tolerance was only evident to morphine or morphine and fentanyl combined in rats pretreated with co-administration of low doses of morphine and fentanyl. This finding is consistent with the functionally selective signaling that has been reported for antinociception and tolerance after morphine and fentanyl binding to the mu-opioid receptor. This research supports the notion that combination therapy and opioid rotation may be useful clinical practices to decrease opioid tolerance and other side effects. PERSPECTIVE: This preclinical study shows that there is a decrease in cross-tolerance between morphine and fentanyl within the periaqueductal gray, which is a key brain region in opioid antinociception and tolerance.
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Registered trials
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