Research ArticlePain

Decreased abundance of TRESK two-pore domain potassium channels in sensory neurons underlies the pain associated with bone metastasis

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Science Signaling  16 Oct 2018:
Vol. 11, Issue 552, eaao5150
DOI: 10.1126/scisignal.aao5150

VEGF, channels, and metastatic pain

Metastatic cancer in the bone is painful. Yang et al. found that the growth factor VEGF, which is well known for its role in tumor-supportive angiogenesis, directly contributes to this pain. Cell cultures and tissue from a rat model of bone metastatic breast cancer revealed that tumor-secreted VEGF activated a negative-feedback pathway through which the expression of the potassium channel TRESK was repressed. Loss of potassium current through TRESK increased the excitability of sensory neurons and made the animals hypersensitive to heat and touch near the bone lesion. Blocking this pathway restored channel activity and alleviated pain in the animals.

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