Fig. 6. Optogenetic inhibition of VP ChAT neurons mitigates the reduction in pain thresholds in persistent pain.
a, b Schematic diagram and a representative image out of 9 for optogenetic (NpHR) inhibition of VP ChAT neurons. c Establishment of pain mouse models. d, e PWT and PWL for both hind paws of NpHR (n = 9) and eGFP (n = 8) mice before, during, and after yellow-light illumination of the right VP, corresponding to before and 24, 48, 72 h after CFA injection. f, g PWT and PWL on the left hind paw of NpHR (n = 8) and eYFP (n = 7) mice before and during yellow light in the right VP in SNI mice. f NpHR: F(1.060, 7.420) = 53.90, P = 0.0001; t = 8.24, df = 7, P = 0.0001, baseline vs SNI; t = 8.75, df = 7, P < 0.001, SNI vs SNI-VP-light. eYFP: F(1.002, 6.010) = 67.52, P = 0.0002; t = 8.19, df = 6, P = 0.0004, baseline vs SNI; t = 0.39, df = 6, P = 0.71, SNI vs SNI-VP-light. g NpHR: F(1.321, 9.245) = 104.3, P < 0.0001; t = 14.98, df = 7, P < 0.0001, baseline vs SNI; t = 14.14, df = 7, P < 0.001, SNI vs SNI-VP-light. eYFP: F(1.224, 7.346) = 236.40, P < 0.0001; t = 14.97, df = 6, P < 0.0001, baseline vs SNI; t = 0.45, df = 6, P = 0.67, SNI vs SNI-VP-light. h–j Representative images and summary showing NpHR-labeled VP ChAT neurons and c-Fos-positive VP neurons from saline (n = 6), CFA (n = 6), and CFA-VP-light (n = 6) mice. k–m Representative images and summary showing NpHR-labeled VP ChAT neurons and c-Fos-positive ChAT and non-ChAT neurons in the VP from Sham (n = 9), SNI (n = 9), and SNI-VP-light (n = 9) mice. One-way repeated-measures ANOVAs with Bonferroni tests and Geisser–Greenhouse corrections were used for (d–g). One-way ANOVAs with Bonferroni tests were used for (i, j, l, m). *P < 0.05; **P < 0.01; ns not significant. Contra contralateral, Ipsi ipsilateral.