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One study compared the effects of high-dose duloxetine, pregabalin, and duloxetine with pregabalin combination therapy in 343 patients with a MNSI score 3 and who did not show improvement in pain with duloxetine or pregabalin monotherapy

Under normoxic conditions HIF1 is hydroxylated and subsequently ubiquitinated for proteasomal degradation, whereas under hypoxic conditions its hydroxylation is blocked leading to its accumulation, dimerization with its beta subunit and subsequent translocation into the nucleus, where it regulates the expression of genes linked to cellular transformation, cell proliferation and angiogenesis [154156]