The Open Pain Journal

2013, 6 : 183-189
Published online 2013 July 26. DOI: 10.2174/1876386320130624001
Publisher ID: TOPAINJ-6-183

RESEARCH ARTICLE
 Electroacupuncture Inhibits Spinal Interleukin-17A to Alleviate Inflammatory Pain in a Rat Model

Xianze Meng1,2 , Lixing Lao1 , Xue-Yong Shen3 , Brian M. Berman1 , Ke Ren4 , Pin-Kang Wei2 and Rui-Xin Zhang1, *
1 Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
2 Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200001, P. R. China
3 Acupuncture College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 P. R. China
4 Department of Neural and Pain Sciences, Dental School, University of Maryland, Baltimore, MD 21201,USA

* Address correspondence to this author at the Center for Integrative Medicine, 685 W. Baltimore Street, MSTF Rm 8-22, Baltimore, MD 21201, USA; Tel: 410-706-1582; Fax: 410-706-1583; E-mail: Rzhan001@umaryland.edu

ABSTRACT

Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund's adjuvant (CFA, 0.08 ml, 40 μg Mycobacterium tuberculosis) into the hind paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 μl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or –IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located in astrocytes and IL-17RA and NR1 are in neurons, the data suggest that EA alleviates pain by modulating glia-neuronal interactions that involve IL-17A, IL-17RA, and NR1 phosphorylation.

Keywords:

Hyperalgesia, Pain, Spinal cord, Interleukin-17A, NMDA, Electroacupuncture, Astrocytes.