Clinical pain, especially chronic pain, is now known to be not just a reflection of sustained noxious input but also, to a large extent, the expression of neural plasticity. By positively modulating the excitatory glutamate/N-methyl-d-aspartate receptor (NMDA-R), polyamines could facilitate central pain sensitization.
Since polyamines mainly originate from dietary intake and gut bacterial metabolism, a polyamine-deficient diet (PD diet) could be a nutritional strategy to counteract the deleterious effect of upregulated NMDA activity and subsequent pain sensitization.
In rat preclinical studies, we demonstrated that a PD diet for several days reverses the sustained pain hypersensitivity associated with experimental neuropathy or monoarthritis in rats and restores the analgesic effect of morphine without inducing the adverse effects commonly induced by NMDA receptor antagonists.
A PD diet also prevented hyperalgesia induced by an inflammation. In contrast, rats fed with a polyamine enriched diet (10-fold, as compared to normal diet level) reveal a strong post-inflammatory hyperalgesia enhancement (proof of concept).
For humans, a polyamine free nutritional formula marketed under the trademark Polydol® by Nutrialys Medical Nutrition represents a new therapeutic strategy for reducing exaggerated acute pain and improving the management of chronic and intractable pain in association with classical analgesics. Clinical trials are ongoing.