Expression levels of the hypothalamic AMPK gene determines the responsiveness of the rats to electroacupuncture-induced analgesia
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
BMC Complementary and Alternative Medicine 2014, 14:211 doi:10.1186/1472-6882-14-211Published: 30 June 2014
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.
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.
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).
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.