Rosiglitazone Alleviates Mechanical Allodynia of Rats with Bone Cancer Pain through the Activation of PPAR-γ to Inhibit the NF-κB/NLRP3 Inflammatory Axis in Spinal Cord Neurons

Figure 3

Rosiglitazone attenuated bone cancer pain (BCP) by activating proliferator-activated receptor-γ (PPAR-γ). (a) Compared to that of rats in the vehicle-treated BCP group, repeated intrathecal injection of rosiglitazone at 50, 100, and 200 μg significantly increased the paw withdrawal threshold (PWT) of BCP rats in a dose-dependent manner from postoperative days (POD) 14–18 ( and vs. the vehicle control group; , two-way repeated measures ANOVA (a)). (b) A single dose of rosiglitazone (50, 100, and 200 μg) reversed mechanical hypersensitivity in the later stages of BCP in a dose-dependent manner (, , and vs. the vehicle control group; , two-way repeated measures ANOVA (b)). (c) The PPAR-γ antagonist GW9662 reversed the analgesic effect of rosiglitazone in BCP rats ( and vs. the BCP+RG group; , two-way repeated measures ANOVA (c)). Rosiglitazone and GW9662 treatment did not affect the basal pain threshold of sham rats ( vs. the vehicle control group; two-way repeated measures ANOVA (c)). (d, e) Representative CATWALK gait analysis results, including print view and timing view in the BCP, BCP+rosiglitazone, and BCP+rosiglitazone+GW9662 groups. Print area is the size of the paw print. Print time represents the related contact time. (f) Compared with those in the BCP group, the percentages of left/right hind paw ratio of maximum contact area, maximum contact maximum intensity, and mean intensity were significantly increased in the group treated with 200 μg rosiglitazone ( and vs. vehicle control group; , one-way ANOVA (f)), which was reversed upon treatment with GW9662 at a dose of 10 mg/kg ( and vs. the BCP+RG group; , one-way ANOVA (f)). Max contact area is the print area during maximum hind paw contact; max contact max intensity is the maximum intensity during maximum hind paw contact; and mean intensity is the average of the hind paw intensity at all time points. All data were calculated as the percentage of the ipsilateral (left)/contralateral (right) hind paw. (g) Western blotting results showed that compared with the vehicle treatment group, rosiglitazone treatment remarkably increased the expression of PPAR-γ in the spine of BCP rats ( vs. the vehicle control group; , one-way ANOVA (g)), which was reversed by preadministration of GW9662 ( vs. the BCP+RG group; , one-way ANOVA (g)). BL: baseline; GW: GW9662; RG: rosiglitazone. N.S: not statistically significant.

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