ArticleNature communications2024
FLT3 signaling inhibition abrogates opioid tolerance and hyperalgesia while preserving analgesia.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Zonisamide attenuates morphine tolerance in association with reduced spinal TLR4/p38 MAPK signaling.Frontiers in pharmacology · 2026Article
- Transcriptome Analysis of Trigeminal Ganglion and Medullary Dorsal Horn in Mice to Identify Potential Targets for Pulpitis-Induced Pain.ACS omega · 2025Article
- Electroacupuncture alleviates pain by activating the MD2/TLR4/NF-κB pathway in the ST36 acupoint.Frontiers in immunology · 2025Article
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Authors and funding
24 authors.
Funding
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Abstract
Navigating the duality of opioids' potent analgesia and side effects, including tolerance and hyperalgesia, is a significant challenge in chronic pain management, often prompting hazardous dose escalation to maintain analgesic effects. The peripheral mu-opioid receptor (MOR) is known to mediate these contradictory effects. Here, we show that the fms-like tyrosine kinase receptor 3 (FLT3) in peripheral somatosensory neurons drives morphine tolerance and hyperalgesia in a male rodent model. We found that chronic morphine treatment increases FLT3 and MOR co-expression, and that inhibiting FLT3 represses MOR-induced hyperactivation of the cyclic adenosine monophosphate (cAMP) signaling pathway, mitigating maladaptive excitatory processes engaged after chronic morphine treatment. Furthermore, in postsurgical or inflammatory models of chronic pain, co-administering morphine with a FLT3-specific inhibitor not only prevents or suppresses tolerance and hyperalgesia but also potentiates the analgesic efficacy of morphine, without aggravating other morphine-induced adverse effects. Our findings suggest that pairing morphine with FLT3 inhibitors could become a promising avenue for chronic pain management to safely harness the power of opioids, without the risk of dose escalation. By enhancing morphine analgesic potency through FLT3 inhibition, this approach could minimize opioid dosage, thereby curtailing the risk of addiction and other opioid-related side effects.
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