Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model

Chronic inflammatory pain is often caused by peripheral tissue damage and persistent inflammation. This disease substantially affects patients' physical and social well-being. We investigated the role of metallothionein-3 (MT3) in modulating complete Freund's adjuvant (CFA)-induced intracellular Zn²⁺ activity in an MT3 knockout mouse model of inflammatory pain in the hind paw. The results demonstrated that increasing intracellular Zn²⁺ levels ameliorate deficits in motor behavior, as well as inflammation in the paw, spleen, and thymus. Furthermore, intracellular Zn²⁺ was crucial in regulating oxidative stress markers (glutathione, superoxide dismutase, catalase, and malondialdehyde) and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in MT3 knockout mice induced with CFA. This study highlights the critical role of MT3 in coordinating the intracellular interaction with Zn²⁺, which is vital for the immune systems's protective functions. These interactions are fundamental for maintaining metal ion homeostasis and regulating the synthesis of various biomolecules in the body.