Tau Accumulation in the Spinal Cord Contributes to Chronic Inflammatory Pain by Upregulation of IL-1β and BDNF
Shuxia Zhang1 · Yeru Chen1 · Yongjie Wang2,3 · Hongwei Wang1 · Dandan Yao1 · Gang Chen11 Department of Anesthesiology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
2 Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou 311121, China
3 Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes, Hangzhou Normal University, Hangzhou 311121, China
Abstract
Microtubule-associated protein Tau is responsible for the stabilization of neuronal microtubules under normal physiological conditions. Much attention has been focused on Tau’s contribution to cognition, but little research has explored its role in emotions such as pain, anxiety, and depression. In the current study, we found a significant increase in the levels of p-Tau (Thr231), total Tau, IL-1β, and brain-derived neurotrophic factor (BDNF) on day 7 after complete Freund's adjuvant (CFA) injection; they were present in the vast majority of neurons in the spinal dorsal horn. Microinjection of Mapt-shRNA recombinant adeno-associated virus into the spinal dorsal cord alleviated CFA-induced inflammatory pain and inhibited CFA-induced IL-1β and BDNF upregulation. Importantly, Tau overexpression was sufficient to induce hyperalgesia by increasing the expression of IL-1β and BDNF. Furthermore, the activation of glycogen synthase kinase 3 beta partly contributed to Tau accumulation. These findings suggest that Tau in the dorsal horn could be a promising target for chronic inflammatory pain therapy.
Keywords
Tau; Infammatory pain; IL-1β; BDNF
