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This is not harmful accumulation but rather the intended therapeutic level

Some of these studies were conducted using liver biopsy in human [10,11]

These studies conducted on rats may translate to humans too in the future due to the similarity in the mesolimbic dopamine system in humans and rats

Those decisions belong to you and your doctor

Small fluctuations are normal

In other words, the amount of mechanical or chemical or thermal, meaning temperature stimuli that can evoke a pain response and how we would rate that response, is much lower at night, and in particular, in the hours between 2:00 AM and 5:00 AM if you're on a kind of standard circadian schedule