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. 2018 Aug 6;115(34):E8057–E8066. doi: 10.1073/pnas.1721815115

Fig. 5.

Fig. 5.

Peripheral MΦ infiltration is critical for nerve injury/neuropathy-induced mechanical and cold hypersensitivity. (A–C) Chemogenetic depletion of peripheral MΦs in MaFIA mice with B/B-HmD administration (2 mg/kg/d for 5 d, starting 6 d after SNI) (A), significantly attenuates SNI-induced ipsilateral hindpaw mechanical (B) and cold hypersensitivity (C), which subsequently returns to predepletion levels 3–4 d after the last B/B-HmD administration. Mean ± SEM; *P < 0.05, **P < 0.01, and ***P < 0.001 vs. respective baselines, sham – B/B-HmD-ipsi group or respective SNI – B/B-HmD-contra group; #P < 0.05, ##P < 0.01, ###P < 0.001 and not significant (ns) vs. SNI – vehicle-ipsi group. (D) Histological confirmation of MΦ (Iba1-red) depletion at day 11 after SNI (after fifth B/B-HmD), and repopulation at day 16 after SNI (5 d after final B/B-HmD) in the sciatic nerves (NF200-green) of MaFIA mice, which are quantified in E. (Scale bars, 200 μm.) (E) Mean ± SEM; ***P < 0.001 vs. respective sham – B/B-HmD-ipsi group; ###P < 0.001 and not significant (ns) vs. respective SNI – vehicle-ipsi groups (n = 2 sections per mouse, 4 mice per group). (F and G) Following MΦ depletion, administration of PD123319 on day 10 (red box) has no additional effect on ipsilateral hindpaw mechanical (F) or cold (G) hypersensitivity. Aqua rectangular boxes in B, C, F, and G, and red rectangular boxes in D and E denote postdrug administration behavioral assessment time points. *P < 0.05, and ***P < 0.001 vs. respective SNI-contra group.