FLT3 signaling inhibition preserves opioid analgesia while abrogating tolerance and hyperalgesia
Jouvenel, A.; Tassou, A.; Thouaye, M.; Ruel, J.; Antri, M.; Leyris, J.-P.; Paquet, A.; Mallie, S.; Sar, C.; Diouloufet, L.; Sonrier, C.; Daubeuf, F.; Bertin, J.; Alves, S.; Venteo, S.; Frossard, N.; Carroll, P.; Mechaly, I.; Rognan, D.; Sokoloff, P.; Dallel, R.; Delmas, P.; Valmier, J.; Rivat, C.
Show abstract
Opioid analgesia is counteracted on chronic use by tolerance and hyperalgesia inducing dose escalation and life-threatening overdoses. Mu opiate receptors (MOR) expressed in primary sensory neurons were recently found to control tolerance and hyperalgesia, but the underlying mechanisms remained elusive. Here we show that genetic inactivation of fms-like tyrosine kinase receptor 3 (FLT3) receptor in sensory neurons abrogates morphine tolerance and hyperalgesia by preventing MOR-induced hyperactivation of the cAMP signaling pathway and subsequent excitatory adaptive processes. Moreover, the specific FLT3 inhibitor BDT001 potentiates morphine analgesia in acute and chronic pain models, without aggravating morphine adverse effects, and reverses tolerance and hyperalgesia once installed. Thus, FLT3 appears as a key regulator of the MOR signaling pathway and its pharmacological blockade shows promise to enhance chronic opioid analgesic efficacy.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Opioidergic activation of descending pain inhibitory system underlies placebo analgesia 97%
- Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation 96%
- ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain 96%
Similar papers in this journal
- MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel 96%
- The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States 94%
- Pain hypersensitivity is dependent on autophagy protein Beclin 1 in males but not females 94%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.