LAUSR

The midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission. We examined the role of pro-inflammatory cytokines (PICs) of the PAG in regulating mechanical hyperalgesia and cold hypersensitivity evoked by diabetes via phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signals. Neuropathic pain was induced by streptozotocin (STZ) in rats and mechanical and cold sensitivity were determined. Western blot analysis and ELISA were used to examine expression of PI3K/Akt/mTOR and PIC signal. p-PI3K/p-Akt/p-mTOR were amplified in the PAG of STZ rats, and blocking PI3K-mTOR in the PAG attenuated neuropathic pain. Also, interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) were elevated in the PAG of STZ rats and their receptors (IL-1R, IL-6R, and TNFR1) were upregulated. Inhibiting PIC receptors alleviated neuropathic pain in STZ rats, accompanied by downregulated PI3K-mTOR. Thus, upregulation of PIC signal in the PAG of STZ rats amplifies PI3K-mTOR and thereby alters the descending pathways in regulating pain transmission.