Mice with high FGF21 serum levels had a reduced preference for morphine and an attenuated development of acute antinociceptive tolerance and physical dependence

Dorval, Louben; Knapp, Brian I.; Majekodunmi, Olufolake A.; Eliseeva, Sophia; Bidlack, Jean M.

doi:10.1016/j.neuropharm.2021.108858

Cited by 8 publications

(6 citation statements)

References 65 publications

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“…This study also found that FGF21 overexpression blunted the magnitude and rate of acute morphine antinociceptive tolerance development, and blunted acute and chronic morphine physical dependence. 91 …”

Section: Resultsmentioning

confidence: 99%

The crosstalk between fibroblast growth factor 21 (FGF21) system and substance use

Wang,

Tyler,

Ilaka

et al. 2024

iScience

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Section: Resultsmentioning

confidence: 99%

The crosstalk between fibroblast growth factor 21 (FGF21) system and substance use

Wang,

Tyler,

Ilaka

et al. 2024

iScience

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“…There is a complex bidirectional relationship between RTK gene expression and opioid dependence. Dorval and colleagues showed that mice that overexpress FGF21, an FGFR ligand (FGF21-Tg mice, 50-fold overexpression), have a reduced preference to morphine in a conditioned place preference paradigm ( Dorval et al, 2022 ). Further, naloxone-precipitated physical dependence behavior, (i.e., number of vertical jumps post-naloxone injection) is depressed in FGF21-Tg mice compared to wildtype littermates, suggesting that acute morphine physical dependence is regulated by FGF21 activity.…”

Section: Involvement Of Receptor Tyrosine Kinase Signaling Opioid-med...mentioning

confidence: 99%

“…More specifically, RTK signaling selectively regulates analgesic tolerance to MOR selective agonists ( Puig et al, 2020a , b ). Emerging evidence also suggests that RTKs could be involved in reduced opioid analgesia against neuropathic pain ( Donica et al, 2014 ; Puig et al, 2020b ), physical dependence ( Rezamohammadi et al, 2020 ; Dorval et al, 2022 ), and reward ( Koo et al, 2014 ; Fetterly et al, 2021 ). Together, these studies suggest that targeting opioid side-effects with RTK inhibitors could constitute a promising strategy to improve opioid safety.…”

Section: Introductionmentioning

confidence: 99%

Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward

Gamble

Williams

Singh

et al. 2022

Front. Syst. Neurosci.

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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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“…Morphine, one of the opioids, is the most widely used analgesic for chronic pain management in the world (Rajput et al 2021). Repeated morphine use can lead to hyperalgesia (Hu et al 2021), antinociceptive tolerance (Dorval et al 2021), physical and psychological dependence (Ahsan et al 2021), as well as morphine withdrawal-induced neuropsychiatric symptoms including anxiety (Wang et al 2016) and depression (Rauf et al 2014), restricting the effective use of the analgesics. In addition to the high costs of morphine use in people with chronic pains, 77% of them are accompanied by a depressive state (Rauf et al 2013), increasing morphine use-related fatality and disability.…”

Section: Introductionmentioning

confidence: 99%

Characterized profiles of gut microbiota in morphine abstinence-induced depressive-like behavior

Ji,

Yan,

Zhang

et al. 2022

Preprint

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Morphine is the most widely used analgesic for pain management worldwide. Abstinence of morphine could lead to neuropsychiatric symptoms including depression. Gut microbiota is believed to contribute to the development of depression. However, the characters and potential role of gut microbiota in morphine abstinence-induced depression remains unclear. In the present study, we first established mice models of morphine abstinence-induced depressive behavior in mice. After dividing the mice into depressive and non-depressive groups, the gut microbiota of the mice was detected by 16S rRNA gene sequencing. The difference in the diversities and abundance of the gut microbiota were analyzed between groups. Then, the representative microbial markers that could distinguish each group were identified. In addition, gene function prediction of the operational taxonomic units (OTUs) with differential abundance between the depressive and nondepressive groups after morphine abstinence was conducted. Our results suggested that four weeks from abstinence of morphine did not change the richness of the gut microbiota. While, morphine abstinence influenced the gut microbial composition. Several specific genera of gut microbiota were identified as markers for each of the groups. Interestingly, the pathway of fatty acid metabolism was found enriched in the OUTs in the depressive group compared with the nondepressive group after morphine abstinence, by gene function prediction. Our data suggested that dysbiosis of gut microbiota was associated with morphine abstinence-induced depressive behavior, possibly by implicating the fatty acid metabolism pathway.

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Mice with high FGF21 serum levels had a reduced preference for morphine and an attenuated development of acute antinociceptive tolerance and physical dependence

Cited by 8 publications

References 65 publications

The crosstalk between fibroblast growth factor 21 (FGF21) system and substance use

The crosstalk between fibroblast growth factor 21 (FGF21) system and substance use

Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward

Characterized profiles of gut microbiota in morphine abstinence-induced depressive-like behavior

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