Miranda, A. L. P. | Search bioRxiv

bioRxiv2025

Dietary zinc restriction induces irreversible allodynia in adult mice

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.

biochemistry↗

bioRxiv2020

Dietary zinc restriction induces nociceptive pain with reduced inflammation in mice

Zinc (Zn) is an essential micronutrient involved in a large diversity of cellular metabolism, included in the physiology of nervous system and pain modulation. There is little evidence for the role of Zn nutritional alternations to the onset and progression of neuropathic and inflammatory pain. We investigate the effects of a zinc restricted diet on the development of pain. Weaned mice were submitted to different diets: AIN-93 (38mg/kg of Zn) and Zn-deficient (AIN-93 with 11mg/kg of Zn), during four weeks. Mechanical allodynia was measured weekly using Von Frey hairs. Plantar assays for cold and heat allodynia, formalin-induced nociception and carrageenan-induced mechanical allodynia were performed at the 4th week. Plasma, DRG and livers samples were obtained for biochemical and metabolomics analysis. Zn deficient diet completely changed mice sensitivity pattern, inducing an intense allodynia evoked by mechanical, cold and heat stimulus since weaning and during four weeks. Showed also an increased sensitivity of neurogenic phase of formalin test but the inflammatory pain behavior was drastically reduced. Zn restriction increased the ATF-3 and SOD-1 levels at DRG and reduced that of GFAP, leading an increase of neuronal activation and oxidative stress, and reduced neuroimmune activity. Plasma TNF was also reduced and metabolomics analyses suggest a downregulation of lipid metabolism of arachidonic acid, reinforcing the impact of Zn restriction to the inflammatory response. Reduction of Zn intake interferes in pain circuits, reducing inflammatory pain, however enhancing nociceptive pain. Accordingly, Zn imbalance could be predisposing factor for NP development. Therefore, dietary zinc supplementation and its monitoring present clinical relevance.

biochemistry↗