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 5

Rosiglitazone attenuates bone cancer pain (BCP) through the activation of proliferator-activated receptor-γ (PPAR-γ) to inhibit the nuclear factor-kappa B (NF-κB)/nod-like receptor protein 3 (NLRP3) inflammatory axis in spinal cord neurons. (a–c) Tumor cell inoculation significantly induced the activation of NF-κB and NLRP3 in the spinal cord of BCP rats ( vs. the sham group; , one-way ANOVA (a–c)). (d, e) Immunofluorescence results showed that in the dorsal horn of the spinal cord of BCP rats, p-NF-κB (red) and NLRP3 (red) were primarily expressed in neurons (green) rather than astrocytes (green) or microglia (green). Lumbar enlargements were collected on day 18 after the operation or cancer cell inoculation. Sections were counterstained with DAPI (blue) to label cell nuclei. The white arrows indicate colocalization of p-NF-κB and NLRP3 with NeuN (neuronal nuclei, neuronal-specific marker), GFAP (glial fibrillary acidic protein, astrocyte specific marker), and IBA-1- (ionized calcium binding adapter molecule 1, microglial specific marker) immunoreactive cells in the spinal dorsal horn, respectively; .  μm. represents the number of experimental animals in each group. (f–i) Repeated intrathecal injection with PDTC, an NF-κB inhibitor, significantly inhibited the established BCP ( and vs. the vehicle control group; , two-way repeated measures ANOVA (i)) and BCP-induced NF-κB/NLRP3 activation ( vs. the vehicle control group; , one-way ANOVA (f–h)). (j–l) Repeated intrathecal injection with MCC950, an NLRP3 inhibitor, significantly inhibited the established BCP ( and vs. the vehicle control group; , two-way repeated measures ANOVA (l)) and BCP-induced NLRP3 activation ( vs. the vehicle control group; , one-way ANOVA (j, k)). (m–o) Rosiglitazone inhibits the BCP-induced activation of the NF-κB/NLRP3 inflammatory axis, whereas GW9662 reversed this effect ( and vs. the vehicle control group; and vs. the BCP+RG group; , one-way ANOVA (m–o)). N.S: not statistically significant.

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

(j)

(k)

(l)

(m)

(n)

(o)