Fig. 10: Optogenetic inhibition of the VPChAT-BLA projection mitigates hyperalgesia and depression- and anxiety-like behaviours in persistent pain.

a Schematic and representative images for unilateral optogenetic inhibition of the VP-BLA ChAT projection. b, c Representative images and summary of numbers of c-Fos(+) BLA neurons in Saline (n = 11), CFA (n = 8), CFA-BLA-light (n = 11) mice. F(2, 27) = 41.18, P < 0.0001; t = 8.68, df = 27, P < 0.0001, saline vs CFA; t = 7.19, df = 27, P < 0.0001, CFA vs CFA-BLA-light. d, e Representative images and summary of numbers of c-Fos(+) BLA neurons in Sham (n = 10), SNI (n = 10), SNI-BLA-light (n = 8) mice. F(2, 25) = 44.24, P < 0.0001; t = 9.00, df = 25, P < 0.0001, sham vs SNI; t = 6.65, df = 25, P < 0.0001, SNI vs SNI + BLA light. f, g Mechanical and thermal thresholds on both hind paws of NpHR and eYFP mice were measured before, during, and after illumination of the right VPChAT-BLA projection, corresponding to before and 24, 48, and 72 h after CFA injection. eYFP-CFA: n = 7 mice; NpHR-CFA: n = 8 mice. h, i Mechanical and thermal thresholds on the left hind paw of NpHR (n = 8) and eYFP (n = 8) mice were measured before and during yellow light illumination of the right VPChAT-BLA projection, 10 days after SNI surgery on the left side. j Schematic diagram showing 3-day bilateral optogenetic inhibition of the VP-BLA ChAT projection in sham and SNI mice. k, l Representative images and summary showing the numbers of c-Fos(+) BLA neurons in Sham, SNI, and SNI-BLA-light mice. n = 15 sections from five mice in each group. m–p Depression-like behaviours in eGFP-Sham (n = 8), SNI (n = 8), and SNI-BLA-light (n = 11) mice. One-way ANOVAs with Bonferroni tests were used in (c, e, l–p). Friedman Repeated-Measures ANOVA on Ranks was used in (f). One-way repeated-measures ANOVAs was used in (g–i). *P < 0.05; **P < 0.01; ns not significant. Scale bars in insets: 50 μm in (b, d); 100 μm in (k).