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For example, in hereditary leiomyomatosis and renal cell cancer (HLRCC), a high level of fumarate caused by genetic mutation of fumarate hydratase induces the succination of Kelch-like ECH-associated protein 1 (KEAP1) accompanied by the consumption of a fumarate molecule 134,135

A Cochrane analysis concluded that there is only modest information about the use of tramadol in neuropathic pain, coming from small, largely inadequate studies with potential risk of bias [134]