Epigallocatechin-3-gallate attenuates bone cancer pain involving decreasing spinal Tumor Necrosis Factor-α expression in a mouse model

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Abstract

Tumor metastasis to bone often elicits a wide array of symptoms, in which pain is a significant factor in catastrophic complications of bone cancer. The complete understanding of bone cancer-related pain is still unknown, while several pathophysiological components have been suggested, from tumor-stimulated osteolysis, nerve compression, stimulations of ion channels, and locally generated inflammatory cytokines. In particular, it has been shown that pro-inflammatory cytokine TNFα-mediated actions are necessary for the development of bone cancer pain. As a member of catechin family in green tea extracts, EGCG (Epigallocatechin-3-gallate) can reduce excess free radicals and attenuate overactive inflammatory signaling including TNFα. In addition, EGCG or its related molecules have been used to control neuropathic pain in various preclinical settings. However, its potential use in bone cancer-caused pain has not yet been reported. Here we show that treating a mouse model of bone cancer by EGCG, results in a dramatic reduction in pain behavior and a significant decrease of TNFα expression within the spinal cord of tumor-bearing mice. Thus, this study reveals an anti-nociceptive role for EGCG in the progression of pain caused by tumor bone metastasis, and highlights a potential scheme by using anti-TNFα as a therapeutic option for osteolytic pain.

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