Role of microglia in reserpine-induced mechanical pain, a model of fibromyalgia

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  • Saitoh Hidetoshi
    Dept. Pharmacol., Sch. Pharm. Fukuoka, IUHW
  • Hosoi Masako
    Dept. Psychosomatic Med., Kyushu Univ. Hosp. Dept. Psychosomatic Med., Grad. Sch. Med. Sci., Kyushu Univ.
  • Tsuda Makoto
    Dept. Mol. Sys. Pharmacol., Grad. Sch. Pharmaceut. Sci., Kyushu Univ.

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Other Title
  • レセルピン誘発線維筋痛症モデルにおけるミクログリアの役割

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<p>Chronic widespread pain is a serious problem in our life; fibromyalgia is a well-known disease that causes chronic widespread pain, which might be ascribed to central sensitization. Repeated injection of reserpine, which depletes monoamines in the nervous system, has been used as an animal model of fibromyalgia. Repeated subcutaneous injection of reserpine induces behaviors associated with pain. Microglia in the spinal cord is one of the conceivable factors for the mechanism of central sensitization. However, it is still unclear whether and how microglia in the specific region of the brain affect pain perception.</p><p>Using CX3CR1-CreERT2 mice, we generated microglia-selective knockout mice of IRF8 or MafB, both of which have been previously confirmed to exhibit reduced symptoms of nerve injury-induced neuropathic pain. We found that these mice showed significant suppression of reserpine-induced mechanical hypersensitivity. Since no apparent morphological activation of microglia was seen in the spinal cord and the prefrontal cortex at 5 days after reserpine injection, we performed single-cell RNA sequencing with 10X Genomics Chromium platform on CD11b- and P2Y12-positive cells in the prefrontal and anterior cingulate cortex. Through a non-biased graph-based clustering analysis, we detected populational change among detected clusters. These results support the application of a concept of microglial regulation of reserpine-induced mechanical pain and also suggest functional alteration of prefrontal microglia in the symptom.</p>

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