Dietary zinc restriction induces irreversible allodynia in adult mice

Matias, D. O.; Santos, B. L. R.; Martins, A. F.; Souza, L. P.; Miranda-Alves, L.; Cardoso, L. E. M.; Miranda, A. L. P.; Lima, L. M. T.

doi:10.1101/2025.06.02.657430

bioRxiv · 10.1101/2025.06.02.657430

Dietary zinc restriction induces irreversible allodynia in adult mice

Matias, D. O.·Santos, B. L. R.·Martins, A. F.·Souza, L. P.·Miranda-Alves, L.·Cardoso, L. E. M.·Miranda, A. L. P.·Lima, L. M. T.

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Abstract

IntroductionNeuropathic pain is a debilitating condition highly prevalent worldwide. One of the main factors related to its development is poor nutrition and micronutrient deficiency in the diet. Essential metals, especially divalent ions as zinc, play crucial roles in the neurobiology of the nervous system, including pain signaling and transmission mechanisms, and metabolism control. The present study aimed to understand the impact of zinc in neuropathic pain, evaluating whether restriction and direct repletion of a dietary zinc could change nociceptive behavior and metabolic parameters in adult mice. MethodsAdult male Swiss mice received a zinc-restricted diet for eight weeks. The repletion group received the restricted diet for four weeks followed by normal zinc diet for another four weeks. Mechanical and heat thermal pain sensitivity were assessed using the von Frey filaments and Hargreaves tests, respectively. ResultsZinc restriction resulted in decreased body weight gain and led to an increased mechanical and thermal sensitivity to heat. Dietary zinc repletion reversed the thermal allodynia and increased weight gain, abdominal adipose tissue, and liver weight compared to a normal zinc diet. No changes were observed concerning food and water intake, glycemic profile, pancreatic morphology and plasma amylin, ConclusionsThe reduction in the bioavailability of dietary zinc promotes metabolic and nociceptive changes in adult mice, inducing allodynia characteristic of neuropathic pain.

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Matias, D. O., Santos, B. L. R., Martins, A. F., Souza, L. P., Miranda-Alves, L., Cardoso, L. E. M., Miranda, A. L. P., Lima, L. M. T.. 2025-06-03. Dietary zinc restriction induces irreversible allodynia in adult mice. https://doi.org/10.1101/2025.06.02.657430

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