Imaging of microglia ⁄ macrophage in an animal model of peripheral inflammatory pain

Microglia are parenchymal tissue–resident macrophage within the central nervous system (CNS) and originate from erythromyeloid precursor cells in the yolk sac. A growing body of evidence suggests that microglia engage in CNS development, homeostasis and diseases, including chronic pain. Peripheral nerve injury and inflammation produce persistent pain hypersensitivity via CNS sensitization, in which activated microglia have critical roles. Activation of microglia occurs at both spinal and supraspinal levels after nerve injury and inflammation; however, their spatial distribu-tion in the intact tissue remains poorly understood. Recently, tissue clearing methods and high–resolution imaging techniques have been greatly advanced, and these techniques will improve our understanding of pain mechanisms. Therefore, we attempted to clarify the three–dimensional localization of microglia in the intact CNS after peripheral inflammation by analyzing the reporter mouse line Iba– 1 (iCre/+); CAG– floxed STOP tdTomato with CUBIC (Clear, Unobstructed Brain ⁄ Body Imaging Cocktails and Computational analysis). In this review, we focus on recent advances in understanding of microglial activation under pathological pain conditions.