Research Article Transcutaneous Neuromodulation at Posterior Tibial Nerve and ST36 for Chronic Constipation
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Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2014, Article ID 560802, 7 pages http://dx.doi.org/10.1155/2014/560802 Research Article Transcutaneous Neuromodulation at Posterior Tibial Nerve and ST36 for Chronic Constipation Nina Zhang,1,2 Zhihui Huang,1,3 Feng Xu,4 Yuemei Xu,4 Jianfeng Chen,5 Jieyun Yin,1 Lin Lin,2 and Jiande D. Z. Chen1,6 1 Ningbo Pace Translational Medical Research Center, Beilun, Ningbo 210029, China 2 Division of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, 300GuangzhouRoad,Nanjing210029,China 3 Division of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China 4 Division of Gastroenterology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 210029, China 5 Ningbo Maida Medical Device Inc., Ningbo 210029, China 6 Division of Gastroenterology and Hepatology, Johns Hopkins Center for Neurogastroenterology, Baltimore, MD 21224, USA Correspondence should be addressed to Lin Lin; [email protected] and Jiande D. Z. Chen; [email protected] Received 15 July 2014; Accepted 3 October 2014; Published 5 November 2014 Academic Editor: Xiaohua Hou Copyright © 2014 Nina Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The aims of this study were to investigate the effects and possible mechanisms of transcutaneous neuromodulation (TN) in patients with chronic constipation. Twelve patients were recruited. The treatment consisted of 2-week TN and 2-week sham-TN which was performed in a crossover design. Bowel habit diary, Patient Assessment of Constipation Symptom (PAC-SYM), Patient Assessment of Constipation Quality of Life (PAC-QOL), and anorectal motility were evaluated. Electrocardiogram was recorded for the assessment of autonomic function during acute TN therapy. It was found that (1) TN improved the frequency of spontaneous defecation. After 2-week TN therapy, 83% patients had more than 3 times bowel movements per week which was significantly different from sham-TN ( = 0.01). (2) TN improved PAC-SYM and PAC-QOL scores ( < 0.001, resp.). (3) TN significantly decreased the threshold volume to elicit RAIR ( < 0.05), ameliorated rectal sensory threshold ( = 0.04), and maximum tolerance ( = 0.04). (4) TN, but not sham-TN, increased the vagal activity ( = 0.01 versus baseline) and decreased the sympathetic activity ( = 0.01, versus baseline). It was concluded that needleless TN at posterior tibial nerve and ST36 using a watch-size stimulator is effective in chronic constipation, and the effect was possibly mediated via the autonomic mechanism. 1. Introduction is characterized by impaired relaxation and coordination of abdominal and pelvic floor muscles during evacuation [6]. Chronic constipation is a common digestive disease which The regular management for constipation is composed of affects 2% to 26.9% of general population1 [ ]. Chronic consti- changes in life style, laxatives, enterokinetic drugs, biofeed- pation is characterized by less frequency of bowel movements back, and surgical procedure. However, the treatment of (<3 per week), difficult defecation, incomplete evacuation, constipation is still unsatisfactory. and other accompanying symptoms [2]. It is considered to Neuromodulation has recently been shown to be effective impair the quality of life and is associated with psychosocial for management of chronic constipation [7]. Percutaneous problems [3]. The annual cost for each patient with chronic tibial nerve stimulation as a new therapeutic option has been constipation is about $7522 in the U.S. [4]. reported to increase stool frequency, decrease the use of Chronic constipation is known to be classified as slow laxatives, and improve the quality of life in patients with transit constipation, outlet obstruction, and both. Slow transit slow transit constipation [8]. During the past decades, elec- constipation is defined as prolonged stool transit (>3days) troacupuncture (EA) has been reported to accelerate gas- through the colon [5]. The outlet obstruction constipation trointestinal motility both in animals and humans [9–11]. EA 2 Evidence-Based Complementary and Alternative Medicine 2 wk TN (group 1) 2 wk TN (group 2) experiments. In each visit, the Patient Assessment of Con- stipation Symptom (PAC-SYM), the Patient Assessment of 2 wk sham-TN (group 2) 2 wk sham-TN (group 1) Constipation Quality of Life (PAC-QOL) questionnaire, and After 1 wk the anorectal motility test were performed. The patients were askedtofilloutthebowelhabitdiaryduringTNorsham- 1 2 3 V V V TN to record the frequency of defecation, time of defecation, Figure 1: Experimental protocol. stool quality, and medication for defecation. Lactulose was permitted for use only when the patient cannot tolerate the symptoms. During the last visit, heart rate variability (HRV) was recorded in addition to the symptoms and motility test at ST36 (Zusanli) was shown to increase gastric emptying in to evaluate vagal activity. patients with functional dyspepsia [10] and accelerate small bowel transit, colonic contractions, and transit in rats [9, 11]. LittlewasfoundintheliteratureonEAfortreatingpatients 2.3. Transcutaneous Neuromodulation (TN). Posterior tibial with constipation. Although a few studies indicated that nerve and the acupoint ST36 (Zusanli, either right leg or left EA has the potential for treating constipation [12, 13], these leg) were chosen for the TN therapy [8, 14]. Two electrodes studies were not well designed; either lack of controls or the were placed for tibial nerve stimulation, one placed at approx- parameters were unclear which made it difficult to reproduce. imately two fingers’ breadth up to the malleolus medialis Moreover, needle insertion was required in these studies with and posterior to the tibia and the other 4 cm above the first either tibial nerve stimulation or electroacupuncture, which electrode. For ST36, one electrode was placed at ST36 and may generate adverse events such as stress and discomfort the other was 4 cm below ST36 along the same meridian. around the insertion area, so that may not be acceptable by The location of sham-TN was applied at nontibial nerve or every patient. In the current study, we hypothesized to use a nonacupoint (not on any meridian). A watch-size digital noninvasive transcutaneous neuromodulation technique, by stimulator (SNM-FDC01, Ningbo Maida Medical Device combining both tibial nerve stimulation and electroacupunc- Inc., Ningbo, China) was used to deliver trains of pulses: train ture to evaluate the treatment outcomes in patients with on-time of 2 sec and off-time of 3 sec, pulse width of 0.5 ms, chronic constipation. pulsefrequencyof25Hz,andamplitudeof2–10mA(atthe Therefore, the aims of this study were to investigate the maximum level tolerated by the subject). TN or sham-TN was effects and possible mechanisms of transcutaneous neuro- performed for 1 hour, twice daily. modulation (TN) for the treatment of chronic constipation. 2.4. Symptoms Assessment. The number of spontaneous defe- 2. Materials and Methods cations per week was the major primary outcome. The bowel movements more than 3 times per week were defined as 2.1. Patients. Adult outpatients, aged 18–75 years, referred complete response [15]. Time of defecation and stool quality to the clinical department at Yinzhou People’s Hospital recorded in the bowel diary were documented. with chronic functional constipation who fulfilled Rome III The PAC-SYM was used to assess constipation associated criteria were enrolled in this study. All the patients had symptoms [16]. The questionnaire included stool symptoms, symptoms for at least one year and failed to respond to abdominal symptoms, and rectal symptoms with a total previous conservative treatment, including laxatives, enemas, number of 12 items. The higher score ranging from 0 to 4 and biofeedback. Patients were not recruited into the study indicated the higher severity of symptom. The PAC-QOL if they had any organic diseases causing constipation or was a validated questionnaire for the assessment of quality neurologic diseases such as multiple sclerosis, rachischisis, of life in patients with chronic constipation [17]. Four sub- Parkinson’s disease, and spinal cord injury. Patients who were scales indicated physical discomfort, psychosocial distress, pregnant or had a history of gastrointestinal surgery except concerns, and satisfaction with a total number of 28 items. appendectomy or cholecystectomy were excluded. The study The lower score represented the better quality of life. protocolwasapprovedbytheEthicalReviewCommittee of Yinzhou People’s Hospital. Written consent was obtained 2.5. Anorectal Motility. The anorectal manometry was per- from all the patients before the study. formed using an eight-channel water perfused system (GAP- 08A, Ningbo Maida Medical Device Inc., Ningbo, China) to 2.2. Experimental Protocol. This is a placebo-controlled study evaluate (1) threshold volume of rectal distention for eliciting (Figure 1). Patients were blinded about the treatment reg- RAIR, (2) anal resting and maximal squeezing pressures, (3) imens and patients who were familiar with acupoints or rectal sensory threshold, desire to defecate, urge threshold, meridian were excluded. After one-week run-in period, all and maximum tolerance, (4) increase