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. Perspective 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.

Local Changes in Microcirculation and the Analgesic Effects of Acupuncture: A Laser Doppler Perfusion Imaging Study

“…2,20 Further studies are necessary to elucidate the mechanism connecting the local and central effects of acupuncture. In addition, acupuncture stimulation results in the local changes of various biological factors, including nitric oxide, 7,8 calcitonin gene-related factor, 9 histamine, 21 phosphorylated extracellular signalregulated kinase, 22 and adenosine triphosphate and its metabolite adenosine. Recently, Goldman et al 23 and Park et al 22 reported that local release or molecular changes such as adenosine or phosphorylated extracellular signal-regulated kinase play an important role in triggering the acupuncture analgesia.…”

Peripheral and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical Resource Guide for Health Care Professionals

“…ERK stimulates the production of Type-1 collagen fibers via transcription factors such as activator protein-1 [115,117]. Interestingly, a recent study by Park et al found that DN at GB34 turned on 236 genes secondary to the ERK cascade [118]. Moreover, blocking the ERK pathway inhibited the anti-nociceptive effects of DN, suggesting that ERK may be the biochemical hallmark of DN analgesia [118].…”

Case Report: Application of Acupuncture to Treat Knee Pain

“…In addition, improved microcirculation coupled with analgesic effects of needle stimulation could bring about long term improvements. Given the self-reported improvement the patient has experienced, acupuncture may be an option for those suffering from arthritis who wish to reduce their reliance on medication [8][9]. One particular issue of note is that the patient is on Plavix, an anticoagulant prescribed to those who are unable to take aspirin as the standard blood thinner (either due to allergy or contradicting drug interactions), which is listed with the side effect of joint pain, and in some instances, the uncommon side effect of acute osteoarthritis.…”