Our purpose was to combine the use of
morphine with clinically available inhibitors of
protein kinase C (PKC), finally potentiating
morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic
morphine combined or not with increasing doses of the PKC-blocker St. John's Wort (SJW) or its main component
hypericin. Phosphorylation of the γ subunit of PKC
enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with
morphine and
hypericin and was prevented in rodent PAG by SJW or
hypericin co-administration with
morphine, inducing a potentiation of
morphine analgesia in thermal
pain. The score of
pain assessment in healthy volunteers were decreased by 40% when
morphine was co-administered with SJW at a dose largely below those used to obtain an
antidepressant or
analgesic effect in both rodents and humans. The SJW/
hypericin potentiating effect lasted in time and preserved
morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of
morphine obtaining the same
analgesic effect. Therefore, SJW and one of its main components,
hypericin, appear ideal to potentiate
morphine-induced
analgesia.