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

Fig. 1.

Fig. 1.

Peripheral AT2R activation mediates neuropathic pain hypersensitivity. (A) Experimental scheme depicting nerve injury-induced neuropathy, pain behavioral assessments, and drug administration timeline in C57BL/6 (B6) mice for B–E (data analysis scheme in SI Appendix, Fig. S1A). (B) Systemic administration of PD123319 (10 mg/kg, i.p.) attenuates SNI-induced mechanical hypersensitivity. Mean ± SEM; *P < 0.05, **P < 0.01, and ***P < 0.001 vs. sham+saline/PD123319 groups; #P < 0.05 and ##P < 0.01 vs. SNI+saline group. (C) Losartan (10 mg/kg, i.p.) has no effects on SNI-induced mechanical hypersensitivity. Mean ± SEM; **P < 0.01 and ***P < 0.001 vs. sham+losartan-ipsilateral (ipsi) group. (D) Intrathecal PD123319 (30 nmol in 10 μL) does not attenuate SNI-induced mechanical hypersensitivity. Mean ± SEM; ***P < 0.001 vs. contralateral (contra) groups; not significant (ns) vs. SNI+saline-ipsi group. (E) Peri-sciatic PD123319 administration (30 nmol in 10 μL) attenuates SNI-induced mechanical hypersensitivity. Mean ± SEM; ***P < 0.001 vs. contra groups; ###P < 0.001 vs. SNI+saline-ipsi group. (F) SNI elevates Ang II levels in injured mouse sciatic nerve, but not in the spinal cord. Mean ± SEM (n = duplicate tissue samples from six mice per group). ***P < 0.001 vs. respective SNI-contralateral groups; not significant (ns) vs. sham/SNI-contralateral or vehicle groups. (G) Experimental scheme depicting cold hypersensitivity assessment, and drug administration timeline in mice subjected to sham/SNI surgery. (H) Systemic administration of PD123319 (10 mg/kg, i.p.) attenuates SNI-induced cold hypersensitivity. Mean ± SEM; *P < 0.05 and ***P < 0.001 vs. sham+PD123319 group; ##P < 0.01 vs. SNI+saline group. Rectangular boxes in B–E and H denote postdrug administration time points for behavioral assessment.