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Received Dec 29, 2017; Accepted Mar 20, 2018
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1. Introduction
Functional constipation (FC) is mainly characterized by a low defecation frequency, defecation difficulty, and incomplete defecation. The prevalence of FC has been high in female and elderly [1]. Based on the pathophysiology, FC is classified as follows: Slow Transit Constipation (STC), Defecatory Disorder (DD), and Normal Transit Constipation (NTC) [2]. Traditional treatment is mainly focused on drugs such as leavening agent, osmotic laxatives, stimulant laxatives, prosecretory agents, and prokinetic agents [3]. Recently, the bile acid regulator has become a widely applied medical therapy [4]. However, there are still a large number of patients who are refractory to medical therapies and there is a need to develop effective therapies for FC.
Neuromodulation has recently been introduced for the treatment of FC, such as sacral nerve stimulation [5] and tibial nerve stimulation [6] with inconclusive results and largely unknown mechanisms. In a previous study, we reported a promising ameliorating effect of transcutaneous neuromodulation (TN) in FC patients [7]. In this method, electrical stimulation was delivered noninvasively via surface electrodes placed at both an acupoint ST36 and the posterior tibial nerve using an external watch-size stimulator. The therapy was home-based and self-administrated. The therapeutic effect of TN was reported to be mediated via the autonomic functions (enhancement of vagal activity and suppression of sympathetic activity) and hypothesized to improve gastrointestinal motility. However, its exact prokinetic mechanisms, especially the involvement of neurotransmitters and bile acids, were still unclear.
Acupuncture and electroacupuncture have been reported to alter various neurotransmitters in both patients with functional gastrointestinal diseases and animal models of constipation, such as serotonin (5-HT) [8, 9], motilin [10], and vasoactive intestinal peptide (VIP) [11, 12]. While little is known about the direct effects of acupuncture or electroacupuncture on bile acid metabolism, which is involved in 5-HT activation [13]. Meanwhile, the abnormal metabolism of bile acids was found in patients with FC [14, 15], indicating their potential roles in colon motility and hormone secretion to influence intestinal transit [16].
Accordingly, this experiment aims to investigate the therapeutic effect of the...