Fig. 4: The somatosensory cortex to lSuC pathway drives mechanical hypersensitization.
From: Deconstruction of a spino-brain–spinal cord circuit that drives chronic pain
a,b, Representative images (a) and quantification (b) of monosynaptic inputs onto lSuCRVM neurons (n = 4). Scale bar, 500 μm. Inset: three-dimensional (3D) reconstruction of cortical input neurons. Dashed circles indicate MOa and SS. MO, motor cortex; SNr, substantia nigra; LHA, lateral hypothalamus; GRN, gigantocellular reticular nucleus; VNC, vestibular nuclei; VM, ventral medial thalamus; PRNc, caudal-pontine reticular nucleus; PB, parabrachial nucleus; RSP, retrosplenial area. c,d, Mechanical thresholds of saline (black, n = 6 in c, n = 7 in d) and CLZ (blue, n = 6 in c, n = 7 in d) infusion into the lSuC of mice expressing hM4D in MOa (c) or SS (d, P = 0.8438, 0.0156 and 0.0156, left to right) for chemogenetic silencing. e, Locomotor traces and CPA scores in mice expressing mCherry (white, n = 6) and hM4D (blue, n = 7) in the SS after SNI (P = 0.0012). f, Mechanical thresholds in non-injured mice (control mice (red, n = 7) or mice with OPRM1+ RVMSC neurons ablated (black, n = 8)) expressing hM3D in SS after daily injection of CLZ into the lSuC 23 h before each von Frey test for 7 consecutive days (shaded). g, Locomotor traces and CPA scores in hM3D (red, n = 7) and mCherry (white, n = 6) mice after repetitive infusion of CLZ into the lSuC (P = 0.0012). See Supplementary Table 1 for detailed statistics. Two-sided Wilcoxon signed-rank test (c,d); two-sided Mann–Whitney test (e,g and control versus ablation in f); Dunn’s multiple comparisons test (before versus after CLZ in f). *P < 0.05, **P < 0.01, ***P < 0.001; #P < 0.05, ##P < 0.01, ###P < 0.001. Mean ± s.e.m.
