Fig. 6: Contralateral S2 → S2 → S1HL circuit mediates contralateral pain-induced hindpaw analgesia.

a Schematic of simultaneous microendoscopic calcium imaging of S2 and S1HL^Glu neurons after optogenetic inhibition of TRAPed contra-S2 neurons. b–e Representative traces (left) and summarized data (right) of spontaneous Ca²⁺ signals as well as the heatmaps of the activities (left) and z-score responses (right) of GCaMP6m⁺ S2 neurons (b, p < 0.0001, c, p < 0.0001; n = 34 cells from 4 mice) and GCaMP6m⁺ S1HL^Glu neurons (d, p < 0.0001, e p < 0.0001; n = 24 cells from 4 mice) after inhibition of TRAPed contra-S2 neurons. f Timeline of chemogenetic inhibition of the contra-S2 → S2 → S1HL circuit in CFA mice with CAP injection in the right forepaw. g Effects of chemogenetic inhibition of contra-S2 → S2 → S1HL circuit on the nociceptive threshold of the left hindpaw in CFA mice with CAP injection in the right forepaw (n = 8 mice per group; von Frey, p = 0.0033; Hot plate, p = 0.0262; Brush, p = 0.0024; Spontaneous pain, p = 0.0032). CAP, capsaicin. Significance was assessed by two-way repeated-measures ANOVA with post hoc comparison between groups in g, two-tailed paired Student’s t-test in b–d, and Wilcoxon matched-pairs signed rank test in e. Data are presented as means ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001. Details of the statistical analyses are provided in Supplementary Data 2. Source data are provided as a Source Data file.