[Express] Roles of TNF-α and IL-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammatio…

A new interesting article has been published in Mol Pain. 2019 May 30:1744806919857981. doi: 10.1177/1744806919857981. and titled:

[Express] Roles of TNF-α and IL-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammatio…

Authors of this article are:

Zhao D, Han DF, Wang SS, Lv B, Wang X, Ma C.

A summary of the article is shown below:

Pain is one of the most common and distressing symptoms suffered by patients with progression of bone cancer; however, the mechanisms responsible for hyperalgesia are not well understood. The purpose of our current study was to determine contributions of the sensory signaling pathways of inflammatory tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and downstream transient receptor potential ankyrin 1 (TRPA1) to neuropathic pain induced by bone cancer. We further determined if influencing these pathways can improve bone cancer pain. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats to induce mechanical and thermal hyperalgesia. ELISA and western blot analysis were used to examine 1) the levels of TNF-α and IL-6 in dorsal root ganglion (DRG); and 2) protein expression of TNF-α and IL-6 receptors (TNFR1 and IL-6R) and TRPA1 as well as intracellular signals (p38-MAPK and JNK). TNF-α and IL-6 were elevated in the DRG of bone cancer rats and expression of TNFR1, IL-6R and TRPA1 was upregulated. In addition, inhibition of TNFR1 and IL-6R alleviated mechanical and thermal hyperalgesia in bone cancer rats, accompanied with downregulated TRPA1 and p38-MAPK and JNK. We revealed specific signaling pathways leading to neuropathic pain during the development of bone cancer, including TNF-α-TRPA1 and IL-6-TRPA1 signal pathways. Overall, our data suggest that blocking these signals is beneficial to alleviate bone cancer pain.

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