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Open Access Research article

Expression levels of the hypothalamic AMPK gene determines the responsiveness of the rats to electroacupuncture-induced analgesia

Sun Kwang Kim1, Boram Sun2, Heera Yoon1, Ji Hwan Lee13, Giseog Lee12, Sung-Hwa Sohn14, Hyunseong Kim1, Fu Shi Quan5, Insop Shim6, Joohun Ha7, Byung-Il Min28 and Hyunsu Bae1*

Author Affiliations

1 Department of Physiology, College of Korean Medicine, Kyung Hee University, 130-701 Seoul, Republic of Korea

2 Department of East-West Medicine, Graduate School, Kyung Hee University, 130-701 Seoul, Republic of Korea

3 Department of Microbiology, Pusan National University, 609-735 Busan, Republic of Korea

4 Department of Physiology, School of Medicine, Ajou University, 443-721 Suwon, Republic of Korea

5 Department of Medical Zoology, School of Medicine, Kyung Hee University, 130-701 Seoul, Republic of Korea

6 Acupuncture & Meridian Science Research Center, Kyung Hee University, 130-701 Seoul, Republic of Korea

7 Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, 130-701 Seoul, Republic of Korea

8 Department of Physiology, School of Medicine, Kyung Hee University, 130-701 Seoul, Republic of Korea

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BMC Complementary and Alternative Medicine 2014, 14:211  doi:10.1186/1472-6882-14-211

Published: 30 June 2014

Abstract

Background

Although electroacupuncture (EA) relieves various types of pain, individual differences in the sensitivity to EA analgesia have been reported, causing experimental and clinical difficulties. Our functional genomic study using cDNA microarray identified that 5’-AMP-activated protein kinase (AMPK), a well-known factor in the regulation of energy homeostasis, is the most highly expressed gene in the hypothalamus of the rats that were sensitive to EA analgesia (“responder”), as compared to the rats that were insensitive to EA analgesia (“non-responder”). In this study, we investigated the causal relationship between the hypothalamic AMPK and the individual variation in EA analgesia.

Methods

Sprague-Dawley (SD) rats were divided into the responder and the non-responder groups, based on EA-induced analgesic effects in the tail flick latency (TFL) test, which measures the latency of the tail flick response elicited by radiant heat applied to the tail. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the expression levels of AMPK mRNA in the hypothalamus of the responder and non-responder rats. Further, we examined whether viral manipulation of the AMPK expression in the hypothalamus modulates EA analgesia in rats.

Results

The real-time RT-PCR analysis showed that mRNA expression levels of AMPK in the hypothalamus of the responder rats are significantly higher than those of the non-responder rats, validating the previous microarray results. Microinjection of dominant negative (DN) AMPK adenovirus, which inhibits AMPK activity, into the rat hypothalamus significantly attenuates EA analgesia (p < 0.05), whereas wild type (WT) AMPK virus did not affect EA analgesia (p > 0.05).

Conclusions

The present results demonstrated that levels of AMPK gene expression in the rat hypothalamus determine the individual differences in the sensitivity to EA analgesia. Thus, our findings provide a clinically useful evidence for the application of acupuncture or EA for analgesia.

Keywords:
Electroacupuncture; Analgesia; 5’-AMP-activated protein kinase; Responder; Nonresponder; Hypothalamus; Adenovirus; Rats