Fig. 3: Morphine targets functionally compromised ACC neurons to relieve chronic pain.
a, SNI protocol for chronic neuropathic pain. b, Log-transformed rate of licking at the injured limb in SNI (red; n = 9) or uninjured controls (grey; n = 9; two-way repeated measures ANOVA; Tukey correction: Pinteraction = 0.0036). c, Heat map of average state occupancy. d, Occupancy of pain and non-pain states in SNI and uninjured mice (two-way repeated measures ANOVA; Tukey correction: Pinteraction < 0.0001). e, AMPS score in SNI and uninjured mice (two-way repeated measures ANOVA; Tukey correction: Pinteraction = 0.0089). f, AMPS score in SNI and uninjured mice 3 weeks post-SNI and morphine (0.5 mg kg−1; intraperitoneal; two-way repeated measures ANOVA; Tukey correction: Pinjury = 0.0085; Ptreatment = 0.0041). g,h, Left: lick-evoked activity in positive (g) and negative (h) Plick neurons before (black) and after SNI (warm colour gradient; yellow = 1 day and red = 3 weeks post-SNI). Right: area under the curve of lick-evoked activity (0–1 s post-onset) in SNI and uninjured mice (two-way repeated measures ANOVA; Tukey correction: Ppositive,interaction < 0.0001; Pnegative,interaction = 0.021). i,j, Lick-evoked activity in positive (i) and negative (j) Plick neurons. Left, lick-evoked activity at baseline (black), 3 weeks post-SNI (red) and 3 weeks post-SNI + morphine (blue). Right, lick-evoked activity 3 weeks post-SNI versus uninjured mice (two-way repeated measures ANOVA; Tukey correction: Ppositive,interaction = 0.035; Pnegative,treatment < 0.0001; Pnegative,injury < 0.0001). k,l, Calcium event rate in positive (k) and negative (l) Plick neurons before and after morphine treatment (two-way repeated measures ANOVA; Tukey correction: Ppositive,treatment = 0.0023; Pnegative,treatment = 0.0124). m, Linear regression predicting lick rate (purple) and pain state occupancy (grey) from the average magnitude of lick-evoked activity 3 weeks post-SNI (top), after morphine (middle) and change between sessions (bottom; Bonferroni-corrected P values displayed). ⋆P < 0.05. Bars, lines or dots are mean; error bars and shaded areas are s.e.m. (see Supplementary Table 1 (rows 25–37) for statistics).
