Fig. 5: Parallel spinothalamic tract pathways drive mechanical hypersensitization.
From: Deconstruction of a spino-brain–spinal cord circuit that drives chronic pain
a, Representative image of transsynaptically labelled thalamic neurons and their terminals in the SS. AAV1-Cre was injected into the spinal cord and AAV8-FLEX(LoxP)-mScarlet into the thalamus. Scale bar, 500 μm. SSp, primary somatosensory cortex; SSs, secondary somatosensory cortex. b, Functional connectivity between the Po or the VPL and retrogradely labelled lSuC-projecting neurons in the SS. Top, optical excitatory postsynaptic current (oEPSC) traces. Bottom, quantification of connectivity. Numbers indicate cells with oEPSC/total recorded. Scale bars, 50 ms and 50 pA. c,d, Mechanical thresholds after injection of saline (black, n = 7 (c, left), n = 5 (c, right), n = 7 (d)) or CLZ (blue, n = 7 (c, left), n = 5 (c, right), n = 7 (d)) into mice expressing hM4D in the SC→VPL pathway (c, left), the SC→Po pathway (c, right) or both pathways (d: P = 0.8125, 0.0156 and 0.0156, left to right). e, CPA scores after silencing the SC→VPL pathway (n = 6), the SC→Po pathway (n = 5) or both pathways (n = 5). f, Mechanical thresholds after daily injection of CLZ into the RVM 23 h before each von Frey test for 7 consecutive days (shaded), in non-injured mice expressing hM3D in the SC→Po pathway (left, n = 5) or in the SC→VPL pathway (right, n = 5). g, CPA scores after repetitive activation of the SC→VPL (n = 5) or SC→Po (n = 5) pathway. Control (black, n = 5). h, Diagram (left) and quantification of texture discrimination (right) in mice in which both the SC→VPL and the SC→Po pathway (yellow, n = 5) were silenced, mice in which the DCN→VPL pathway (white, n = 6) was silenced or wild-type (WT) mice without manipulation (grey, n = 5) (P = 0.0625, 0.0313 and 0.1250, left to right). i, Summary circuitry diagram for pain sensitization and touch or tactile sensation. Dashed line indicates hypothetical interneurons connecting the OPRM1+ inhibitory inputs to the excitatory STT output pathway. See Supplementary Table 1 for detailed statistics. Two-sided Wilcoxon signed-rank test (c,d,h); one-way ANOVA (e); non-parametric ANOVA (f,g). *P < 0.05, **P < 0.01, ***P < 0.001. Mean ± s.e.m.
