There is a compelling body of evidence that
N-methyl-d-aspartate receptors (
NMDA-R) play a critical role in the development and maintenance of
pain hypersensitivity. However, long-term treatments with
NMDA-R antagonists are limited by unacceptable side effects. Since
polyamines modulate the functioning of
NMDA-R and mainly originate from normal dietary intake and bacterial metabolism in the gut, we developed a nutritional
therapy based on dietary
polyamine deficiency. Here, we reported that a
polyamine deficient diet (PD diet) for 7 days prevented the enhancement of
tyrosine phosphorylation of the spinal NR2B subunit-containing
NMDA-R associated with
inflammation in rats. Based on these data, we studied the ability of PD diet to prevent long-lasting
pain hypersensitivity associated with tissue injury on one hind paw by evaluating long-lasting changes in both mechanical nociceptive threshold and weight bearing. A PD diet strongly reduced long-lasting
hyperalgesia induced by
inflammation or incision, especially in
fentanyl-treated rats. Moreover a PD diet also prevented the exaggerated
hyperalgesia induced by a second
inflammation performed 7 days after the first one. A PD diet also opposed paradoxical
hyperalgesia induced by non-nociceptive environmental stress in rats with
pain and
opioid experiences. A PD diet reversed
pain hypersensitivity associated with monoarthritis or neuropathy and restored the
analgesic effect of
morphine. Since PD diet was devoid of any noticeable side effects, this nutritional
therapy could be part of an effective and safe strategy for pre-emptive
analgesia and for reducing the transition from acute to
chronic pain and its outcomes in various
pain syndromes.