title: From peripheral to central: the role of ERK signaling pathway in acupuncture analgesia.
abstract: Despite accumulating evidence of the clinical effectiveness of acupuncture, its mechanism remains largely unclear. We assume that molecular signaling around the acupuncture needled area is essential for initiating the effect of acupuncture. To determine possible bio-candidates involved in the mechanisms of acupuncture and investigate the role of such bio-candidates in the analgesic effects of acupuncture, we conducted 2 stepwise experiments. First, a genome-wide microarray of the isolated skin layer at the GB34-equivalent acupoint of C57BL/6 mice 1 hour after acupuncture found that a total of 236 genes had changed and that extracellular signal-regulated kinase (ERK) activation was the most prominent bio-candidate. Second, in mouse pain models using formalin and complete Freund adjuvant, we found that acupuncture attenuated the nociceptive behavior and the mechanical allodynia; these effects were blocked when ERK cascade was interrupted by the mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) inhibitor U0126 (.8 μg/μL). Based on these results, we suggest that ERK phosphorylation following acupuncture needling is a biochemical hallmark initiating the effect of acupuncture including analgesia.
  
  
  CONCLUSIONS
  This article presents the novel evidence of the local molecular signaling in acupuncture analgesia by demonstrating that ERK activation in the skin layer contributes to the analgesic effect of acupuncture in a mouse pain model. This work improves our understanding of the scientific basis underlying acupuncture analgesia.
authors: Studies of Translational Acupuncture Research, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Republic of Korea; Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Ji-Yeun
authors: JY
authors: Park
authors: Asian Medicine and Acupuncture Research, Department of Physical Medicine and Rehabilitation, Chapel Hill, North Carolina; Center for Pain Research and Innovation, UNC School of Dentistry, Chapel Hill, North Carolina.
authors: Jongbae J
authors: JJ
authors: Park
authors: Dongguk University Research Institute of Biotechnology, Seoul, Republic of Korea.
authors: Songhee
authors: S
authors: Jeon
authors: Studies of Translational Acupuncture Research, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Republic of Korea.
authors: Ah-Reum
authors: AR
authors: Doo
authors: Studies of Translational Acupuncture Research, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Republic of Korea; Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Seung-Nam
authors: SN
authors: Kim
authors: Studies of Translational Acupuncture Research, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Republic of Korea.
authors: Hyangsook
authors: H
authors: Lee
authors: Studies of Translational Acupuncture Research, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Republic of Korea; Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Younbyoung
authors: Y
authors: Chae
authors: Center for Pain Research and Innovation, UNC School of Dentistry, Chapel Hill, North Carolina.
authors: William
authors: W
authors: Maixner
authors: Studies of Translational Acupuncture Research, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Republic of Korea; Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors: Hyejung
authors: H
authors: Lee
authors: Studies of Translational Acupuncture Research, Acupuncture and Meridian Science Research Center, Kyung Hee University, Seoul, Republic of Korea; Carolina Asia Center, UNC-Chapel Hill, Chapel Hill, North Carolina. Electronic address: acufind@khu.ac.kr.
authors: Hi-Joon
authors: HJ
authors: Park
mesh_terms: D015667:Acupuncture Analgesia; D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005557:Formaldehyde; D005620:Freund's Adjuvant; D015870:Gene Expression; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010146:Pain / Q000503:physiopathology*; D059408:Pain Management / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012879:Skin Physiological Phenomena; D013997:Time Factors
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D005557:Formaldehyde; D005620:Freund's Adjuvant; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Acupuncture analgesia; extracellular signal–regulated kinase; mouse pain model; skin tissues