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Neuron-restrictive silencer factor (NRSF) was significantly upregulated in the injury-related DRGs of partial ligation of the sciatic nerve [113] and sarcoma-inoculated murine model [114], combining with the targeted Oprm1 gene in a sequence-specific manner and reducing the expression of the latter via HDAC-involved mechanisms [113], which is one of their main functions in regulating gene transcription

These side effect are is often reduced by taking prolonged released formulation or taking metformin with food

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Yet for a significant subset of men on TRT, that is exactly what happens, and understanding why requires looking past total testos