title: Inhibition of Spinal Interlukin-33/ST2 Signaling and Downstream ERK and JNK Pathways in Electroacupuncture Analgesia in Formalin Mice.
abstract: Although acupuncture is widely used to manage pain, it remains highly controversial, largely due to the lack of a clear mechanism for its benefits. Here, we investigated the role of IL-33, a novel interleukin (IL)-1 family member, and its receptor ST2 in the analgesic effects of electroacupuncture (EA) on formalin-induced inflammatory pain. The results showed that 1) EA stimulation of ipsilateral Zusanli (ST 36) and Yanglingquan (GB 34) acupoints for 30 min remarkably suppressed the two phases of formalin-induced spontaneous pain; 2) subcutaneous or intrathecal administration of recombinant IL-33 (rIL-33) significantly inhibited the analgesic effect of EA, whereas the ST2 antibody potentiated EA analgesia in formalin mice; 3) EA treatment decreased the up-regulation of IL-33 and ST2 protein following formalin injection; and 4) the suppression of the formalin-induced expression of spinal phosphorylated ERK and JNK induced by EA treatment was significantly attenuated following subcutaneous rIL-33 delivery, and was further decreased by the ST2 antibody. These data suggest that EA alleviates formalin-induced inflammatory pain, at least partially, by inhibiting of spinal IL-33/ST2 signaling and the downstream ERK and JNK pathways.
authors.affiliation: Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; Neuroscience and Neuroengineering Center, Med-X Research Institute Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Shenbin
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Mengting
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Mi
mesh_terms: D000818:Animals; D015671:Electroacupuncture; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005557:Formaldehyde / Q000633:toxicity; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000378:metabolism* / Q000627:therapeutic use; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D018123:Receptors, Interleukin / Q000378:metabolism
chemical_list: C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D018123:Receptors, Interleukin; D005557:Formaldehyde; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4