Zinc reverses NMDA-related hyperalgesia/allodynia in mice

[Caedar]

Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit
Nature Neuroscience 14, 1017–1022 (2011)

Abstract: Zinc is abundant in the central nervous system and regulates pain, but the underlying mechanisms are unknown. In vitro studies have shown that extracellular zinc modulates a plethora of signaling membrane proteins, including NMDA receptors containing the NR2A subunit, which display exquisite zinc sensitivity. We created NR2A-H128S knock-in mice to investigate whether Zn2+–NR2A interaction influences pain control. In these mice, high-affinity (nanomolar) zinc inhibition of NMDA currents was lost in the hippocampus and spinal cord. Knock-in mice showed hypersensitivity to radiant heat and capsaicin, and developed enhanced allodynia in inflammatory and neuropathic pain models. Furthermore, zinc-induced analgesia was completely abolished under both acute and chronic pain conditions. Our data establish that zinc is an endogenous modulator of excitatory neurotransmission in vivo and identify a new mechanism in pain processing that relies on NR2A NMDA receptors. The study also potentially provides a molecular basis for the pain-relieving effects of dietary zinc supplementation.

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This is an important finding because NMDA receptors govern the development of central sensitization in the human body. Although not all chronic pelvic pain patients experience central sensitization, some proportion does, and it looks like they might benefit from zinc supplementation to combat that component. The study showed that zinc supplementation "almost completely reversed thermal hyperalgesia and mechanical allodynia in both [inflammatory] and [neuropathic] models of chronic pain. The effect of zinc was observed at a time point at which inflammatory and neuropathic pain had fully developed."

[webslave]

Interesting. I have long advocated zinc supplements.

My protocol is outdated now, but makes for interesting reading nonetheless
https://ucpps.men/prostatitis-tips-things-that-help-and-hurt

[Caedar]

Especially for those who consume alcohol, as ethanol can reduce zinc absorption in the intestines and increase zinc & magnesium excretion (Mg is another important modulator of NMDA receptors). I had a few beers tonight for the Superbowl, and although my pelvic floor pains remained about the same (almost nothing nowadays), my allodynia cranked up quite a bit. And then I found this paper; seems to make sense.