Inhibition of Spinal Interlukin-33/ST2 Signaling and Downstream ERK and JNK Pathways in Electroacupuncture Analgesia in Formalin Mice

Ping Han; Shenbin Liu; Mengting Zhang; Jing Zhao; Yanqing Wang; Gencheng Wu; Wenli Mi

doi:10.1371/journal.pone.0129576

Inhibition of Spinal Interlukin-33/ST2 Signaling and Downstream ERK and JNK Pathways in Electroacupuncture Analgesia in Formalin Mice

PLoS One. 2015 Jun 12;10(6):e0129576. doi: 10.1371/journal.pone.0129576. eCollection 2015.

Authors

Ping Han¹, Shenbin Liu², Mengting Zhang², Jing Zhao², Yanqing Wang², Gencheng Wu², Wenli Mi²

Affiliations

¹ 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.
² 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Electroacupuncture*
Extracellular Signal-Regulated MAP Kinases / metabolism
Formaldehyde / toxicity
Interleukin-1 Receptor-Like 1 Protein
Interleukin-33 / metabolism*
Interleukin-33 / therapeutic use
MAP Kinase Kinase 4 / metabolism
MAP Kinase Signaling System*
Male
Mice
Mice, Inbred BALB C
Neuralgia / drug therapy
Neuralgia / etiology
Neuralgia / metabolism
Neuralgia / therapy*
Receptors, Interleukin / metabolism

Substances

Il1rl1 protein, mouse
Interleukin-1 Receptor-Like 1 Protein
Interleukin-33
Receptors, Interleukin
Formaldehyde
Extracellular Signal-Regulated MAP Kinases
MAP Kinase Kinase 4

Grants and funding

This work was supported by the National Key Basic Research Program of China (2013CB531906), the National Natural Science Foundation of China (31000495, 81171045, 81371247, and 81473749) and the National Natural Science Foundation of Shanghai (15ZR1402800).