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Local (and systemic) estradiol can stimulate lesion production of PGE2, which can activate pain fibers, enhance neuronal invasion of lesions by stimulating production of NGF and other neurotrophins, and promote sprouting of nociceptors that contribute persistent inflammatory pain and inhibit neuronal apoptosis

A detoxification impairment leads to high levels of inflammation and nutrient depletion (because your body is frantically trying to detox)