P66shc in the spinal cord is an important contributor in complete Freund's adjuvant induced inflammatory pain in mice

• DOI: 10.1016/j.bbrc.2023.03.028
• Publication Date: 2023-03-11T06:53:04Z
• Authors: Qianqian Chen; Juji Dai; Fubei Nan; Jun Xu; Shuangdong Chen
• Keywords: Inflammation; Mice; Src Homology 2 Domain-Containing, Transforming Protein 1; Spinal Cord; Inflammasomes; Hyperalgesia; Freund's Adjuvant; NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Pain; Reactive Oxygen Species; 3. Good health

The aim of this study is to investigate whether p66shc is involved in inflammatory pain and the potential molecular mechanisms of p66shc in inflammatory pain.Inflammatory pain model was established by complete Freund's adjuvant (CFA) injection. Paw withdrawal latency (PWL) and paw withdrawal frequency (PWF) was recorded. The expression of spinal p66shc were determined by immunohistochemical staining, immunofluorescence staining. P66shc knockdown was performed by an adeno-associated virus (AAV) vector infusion. NLRP3 inflammasome complexes were determined by Western blot. DHE staining was used to evaluate reactive oxygen species (ROS) generation.P66Shc expression was progressively elevated in spinal cord of inflammatory pain mice, and p66Shc knockdown in vivo significantly attenuated CFA injection triggers hyperalgesia. Furthermore, knockdown of p66Shc significantly inhibited ROS production and NOD-like receptor protein 3 (NLRP3) inflammasome activation, which were reversed by a ROS donor (t-BOOH). However, post-treatment with nigericin, a agonist of NLRP3, reversed AAV-shP66shc analgesic effect.Spinal p66shc may facilitate the development of inflammatory pain by promoting the activation of NLRP3 inflammasome through ROS.