Fig. 6

Role of IL-6/STAT3 signal pathway in the comorbidity of neuropathic pain/depression. A Expression of IL-6, p-STAT3 and STAT3 in PrL were explored on weeks 5 following the SNI (n = 3 or 4, unpaired t test, **p = 0.0034, ***p = 0.0003 versus the sham group). B Incubation of IL-6 increased the expression of p-STAT3 and Acp5 in PC12 cells (n = 3, unpaired t test, *p = 0.0384, ****p < 0.0001 versus the vehicle group). C IL-6R expression was colocalized with NeuN-positive cells, but not GAFP-positive cells or Iba1-positive cells (scale bars, 20 µm, n = 2). D Injective schematic of the AAV-Il-6R-shRNA. E Representative images of viral expression within PrL region (scale bars, 500 µm). F Intra-PrL microinjection AAV-IL-6R-shRNA decreased the p-STAT3 or Acp5 upregulation induced by SNI (n = 3, One-way ANOVA, F_(2,6) = 6.756, *p = 0.0291, F_(2,6) = 11.03, **p = 0.0098 versus the correspondence scramble group.) G Knockdown of IL-6R in PrL pyramidal neurons increased the number of action potential in comorbid group (n = 15 or 20 in each group, Two-way ANOVA, ****p < 0.0001 versus the correspondence scramble group). H IntraPrL injection of AAV-IL-6R-shRNA decreased the immobility time induced by SNI in the FST (n = 8 in each group, unpaired t-test, ****p < 0.0001 versus the correspondence scramble group). I Distance in the central zone (left) and the outer zone (right) in OFT were examined following the intraPrL injection of AAV-IL-6R-shRNA (n = 7 or 8 in each group, unpaired t test, ****p < 0.0001 versus the correspondence scramble group). J Time spent and entries number in the open arms (left) and the closed arms (right) was measured in the EPM test following knockdown of IL-6R in PrL pyramidal neurons. (n = 8 in each group, unpaired t test, ***p = 0.0002, ****p < 0.0001 versus the correspondence scramble group). Data are expressed as mean ± SEM