Figure 5.
HIS abolishes neuroinflammation and central sensitization in the spinal cord of CPIP mice.
(A) Representative images of Iba1 (green, Alexa Fluor 488) immunofluorescence staining in the bilateral spinal dorsal horn in CPIP mice subjected to exercise or no exercise. Iba1 fluorescence was reduced in CPIP mice subjected to exercise. The righthand images (bar: 100 μm) are high magnifications of the boxes in the lefthand images (bar: 200 μm). (B, C) Iba1 fluorescence intensity and numbers of Iba1-positive microglia (n = 3 mice/group). **P < 0.01, ***P < 0.001 and ****P < 0.0001, vs. no exercise mice in the CPIP group. (D, E) After HIS exercise, bilateral IL-1β, IL-6, and TNF-α cytokine levels were decreased, and IL-4 and IL-10 levels were increased in CPIP mice (n = 9 mice/group). ****P < 0.0001, vs. no exercise mice in the CPIP group. (F) Representative recordings of spontaneous spikes from spinal WDR neurons in CPIP mice subjected to exercise or no exercise. Spontaneous WDR neuron spikes were reduced in CPIP mice subjected to exercise. (G) The spontaneous firing rate of WDR neurons in CPIP mice subjected to exercise was significantly lower than that of CPIP mice that did not engage in exercise (n = 8 mice in the no exercise group and n = 12 mice in the exercise group, n = 29–46 cells). **P < 0.01, vs. no exercise CPIP mice. All data in B–E are presented as the mean ± SEM, and the data in G are presented as the median ± IQR, and were analyzed by two-tailed unpaired Student’s t-test (B-E) or Mann-Whitney U test (G). Detailed statistical information is shown in Additional Table 2 and Additional file 1 (136.8KB, pdf) . Contra: Contralateral; Exercised: mice were submitted to chronic postischemia pain and performed high-intensity swimming; Iba1: ionized calcium binding adaptor molecule 1; IL: interleukin; IOD: integrated optical density; Ipsi: ipsilateral; Non-exercised: mice were submitted to chronic postischemia pain and were not performed swimming; TNF-α: tumor necrosis factor-α; WDR: wide dynamic range.
