Interaction between astrocytic colony stimulating factor and its receptor on microglia mediates central sensitization and behavioral hypersensitivity in chronic post ischemic pain model
2018
Abstract Accumulation of
microgliaoccurs in the dorsal horn in the
rodentmodel of chronic post ischemic pain (CPIP), while the mechanism how
microgliaaffects the development of persistent pain largely remains unknown. Here, using a
rodentmodel of CPIP induced by ischemia–reperfusion (IR) injury in the hindpaw, we observed that microglial accumulation occurred in the ipsilateral dorsal horn after ischemia 3h, and in ipsilateral and contralateral dorsal horn in the rats with ischemia 6h. The accumulated
microgliareleased BDNF, increased neuronal excitability in dorsal horn, and produced pain behaviors in the modeled
rodents. We also found significantly increased signaling mediated by astrocytic colony-stimulating factor-1 (CSF1) and microglial CSF1 receptor (CSF1R) in dorsal horn in the ischemia 6h modeled rats. While exogenous M-CSF induced microglial activation and proliferation, BDNF production, neuronal hyperactivity in dorsal horn and behavioral hypersensitivity in the naive rats, inhibition of astrocytic CSF1/microglial CSF1R signaling by fluorocitric or PLX3397 significantly suppressed microglial activation and proliferation, BDNF upregulation, and neuronal activity in dorsal horn, as well as the mechanical
allodyniaand thermal
hyperalgesia, in the rats with ischemia 6h. Collectively, these results demonstrated that glial CSF1/CSF1R pathway mediated the microglial activation and proliferation, which facilitated the nociceptive output and contributed to the chronic pain induced by IR injury.
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