Src family kinases involved in CXCL12-induced loss of acute morphine analgesia.

摘要: Abstract Functional interactions between the chemokine receptor CXCR4 and opioid receptors have been reported in brain, leading to a decreased morphine analgesic activity. However cellular mechanisms responsible for this loss of analgesia are largely unknown. Here we examined whether Src family-kinases (SFK)-linked induced by contributed acute could represent new physiological anti-opioid signaling pathway. In way, showed immunohistochemistry western blot that CXCL12 rapidly activated SFK phosphorylation vitro primary cultured lumbar rat dorsal root ganglia (DRG) but also vivo DRG spinal cord. We activation occurred sub population sensory neurons, microglia nerve terminals expressing mu-(MOR) delta-opioid (DOR) receptor. addition described is detected MOR- DOR-immunoreactive neurons vivo, demonstrated an intrathecal administration (1 μg) significantly attenuated subcutaneous (4 mg/kg) analgesia. Conversely, pretreatment with potent antagonist (5 μg) enhanced Similar effects were obtained after injection specific inhibitor, PP2 (10 μg). Furthermore, abrogated CXCL12-induced decrease suppressing conclusion, our data highlight linked family kinases activation.