Zinc deficiency disrupts pain signaling promoting nociceptive but not inflammatory pain in mice.
Cleverton Kleiton F LimaTháyna SisnandeRafaela Vieira SilvaVanessa Domitilla C S DA SilvaJulio J DO AmaralSoraya M OchsBruna L R Dos SantosAna Luísa Palhares MirandaLuís Maurício T R LimaPublished in: Anais da Academia Brasileira de Ciencias (2023)
Zinc (Zn) is an essential micronutrient involved in the physiology of nervous system and pain modulation. There is little evidence for the role of nutritional Zn alternations to the onset and progression of neuropathic (NP) and inflammatory pain. The study investigated the effects of a zinc restricted diet on the development of pain. Weaned mice were submitted to a regular (38 mg/kg of Zn) or Zn deficient (11 mg/kg of Zn) diets for four weeks, pain responses evaluated (mechanical, cold and heat allodynia; formalin- and carrageenan-induced inflammatory hypernociception), plasma and tissues collected for biochemical and metabolomic analysis. Zn deficient diet inhibited animal growth (37%) and changed mice sensitivity pattern, inducing an intense allodynia evoked by mechanical, cold and heat stimulus for four weeks. The inflammatory pain behavior of formalin test was drastically reduced or absent when challenged by an inflammatory stimulus. Zn restriction also reduce plasma TNF, increase neuronal activation, oxidative stress, indicating a disruption of the immune response. Liver metabolomic analyses suggest a downregulation of lipid metabolism of arachidonic acid. Zn restriction since weaned disrupts pain signaling considerably and reduce inflammatory pain. Zn could be considered a predisposing factor for the onset of chronic pain such as painful neuropathies.
Keyphrases
- chronic pain
- neuropathic pain
- pain management
- oxidative stress
- heavy metals
- immune response
- spinal cord
- spinal cord injury
- physical activity
- cell proliferation
- rheumatoid arthritis
- gene expression
- weight loss
- high fat diet induced
- type diabetes
- diabetic rats
- dna damage
- signaling pathway
- single molecule
- toll like receptor
- brain injury
- induced apoptosis
- cerebral ischemia
- replacement therapy