Glial IL-33 signaling through an ST2-to-CXCL12 pathway in the spinal cord contributes to morphine-induced hyperalgesia and tolerance
Xueming Hu, Wei Yang, Meng-Ting Zhang, Lixia Du, Jia-He Tian, Jianyu Zhu, Yu Chen, Feng Hai, Shenbin Liu, Qi‐Liang Mao‐Ying, Yu‐Xia Chu, Hong Zhou, Yanqing Wang, Wen‐Li Mi
Abstract
, which also reduced morphine-enhanced astroglial activation and excitatory synaptic transmission. Furthermore, a pathway mediated by tumor necrosis factor receptor–associated factor 6 (TRAF6) and the kinase JNK in astrocytes was required for IL-33–mediated hyperalgesia and tolerance through promoting the production of the chemokine CXCL12 in the spinal cord. The findings suggest that targeting IL-33–ST2 signaling could enable opioids to produce sustained analgesic effects in chronic pain management.
Topics & Concepts
HyperalgesiaMorphineMedicineSpinal cordPharmacologyAnalgesicChemokineCytokineNociceptionReceptorInflammationImmunologyInternal medicinePsychiatryIL-33, ST2, and ILC PathwaysAsthma and respiratory diseasesDermatology and Skin Diseases