Fig. 6.

AT2R expression in the hematopoietic lineage is critical for nerve injury/neuropathy-induced mechanical and cold hypersensitivity. (A) Schematic showing generation of Agtr2-WT and Agtr2-KO bone marrow chimeras, and subsequent induction of nerve-injury/neuropathy for pain-related behavioral assessment. (B) SNI induces significant mechanical (Left) and cold hypersensitivity (Right) in Agtr2-WT chimeras, which could be attenuated by systemic administration of the AT2R antagonist PD123319 (10 mg/kg, i.p.). In contrast, Agtr2-KO chimeras show significantly attenuated mechanical (Left) and cold hypersensitivity (Right) upon SNI induction, indicating the critical role of MΦ AT2R in the induction and maintenance of neuropathic pain hypersensitivity. Mean ± SEM; *P < 0.05 and ***P < 0.001 vs. Agtr2-WT or Agtr2-KO sham-ipsi groups; ^#P < 0.05, ^##P < 0.01, and ^###P < 0.001 vs. Agtr2-WT SNI-ipsi group. Rectangular boxes in B denote postdrug administration behavioral assessment time points. (C) Representative confocal microscopic images of sciatic nerve sections from Agtr2-WT and Agtr2-KO bone marrow chimeras 15 d after SNI. Elevated Iba1 expression (red) is observed within the ipsilateral, but not contralateral nerves of Agtr2-WT (Upper) and Agtr2-KO (Lower) bone marrow chimeras. NF200: green; DAPI: blue. (Scale bars, 200 µm.) (D) Microglial proliferation/density (Iba1: red, DAPI: blue) in spinal cord dorsal horn from Agtr2-WT and Agtr2-KO bone marrow chimera mice, 10 d after sham/SNI surgery. (Scale bars, 50 µm.)