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Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome
Urological Science xxx (2017) 1e6
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Original article
Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome Min-Hsin Yang a, b, Yu-Hui Huang c, d, Yu-Fen Lai e, Sheng-Wei Zeng c, Sung-Lang Chen a, d, * a
Department of Urology, Chung Shan Medical University Hospital, Taichung, Taiwan Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan d School of Medicine, Chung Shan Medical University, Taichung, Taiwan e Department of Physical Therapy, Chung Shan Medical University Hospital, Taichung, Taiwan b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 December 2016 Received in revised form 17 February 2017 Accepted 21 March 2017 Available online xxx
Objective: The aim of this study was to compare the effectiveness of electromagnetic stimulation (EMS) versus electrostimulation plus biofeedback (ESB) for the treatment of refractory chronic pelvic pain syndrome (CPPS) in men. Materials and Methods: A total of 23 male refractory CPPS patients were included in the study. EMS was applied for 30 minutes, three times weekly, for 6 weeks, for pelvic floor rehabilitation. We retrospectively compared the outcomes with 22 male refractory CPPS patients treated with ESB twice a week for 2 weeks, and later once a week for 4 weeks. Each ESB session lasted 45 minutes, including biofeedback (15 minutes) followed by electrostimulation (30 minutes). The outcome measures included the National Institutes of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), International Prostate Symptom Score (IPSS), and a visual analogue score for pain from baseline to 12 weeks after completion of treatment. Results: Significantly reduced pain, improved quality of life (QoL), and lowered total score of the NIHCPSI were observed in both groups (all p < 0.05). The ESB group also demonstrated improvement in the urinary subscore of the NIH-CPSI. No significant differences were found between the groups in the urinary score measures of the NIH-CPSI. The mean pain score (p ¼ 0.035), QoL (p ¼ 0.012), and total score (p ¼ 0.009) improved significantly in the ESB group compared with EMS group. Total IPSS and visual analogue score improved significantly after treatment in both groups. However, no significant differences were noted between the groups in the total and subdomain sums of the IPSS. Conclusion: Both EMS and ESB physical therapy of the pelvic floor muscle effectively reduce pain, increase the QoL, and improve urinary tract symptoms in male CPPS patients who are refractory to medical treatments. The combination therapy of ES plus biofeedback demonstrates additional benefits in pain and QoL when compared with EMS alone. Copyright © 2017, Taiwan Urological Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: chronic pelvic pain syndrome chronic prostatitis electromagnetic stimulation electrostimulation biofeedback
1. Introduction Chronic pelvic pain syndrome (CPPS) is a bothersome condition with a main manifestation represented by pelvic region pain, with or without lower urinary tract symptoms, lasting >3 months in the absence of infection or other obvious pathology.1 It presents as prostatitis-like symptoms and affects around 2.2e9.7% of male
* Corresponding author. Department of Urology, Chung-Shan Medical University Hospital, 110 Chien-Kuo North Road, Section 1, Taichung 402, Taiwan E-mail address: [email protected] (S.-L. Chen).
patients and accounts for about 3% of male outpatient visits.2,3 The negative impact on quality of life (QoL) is enormous, as approximately one third of these patients experience a relapse of symptoms a year or more after medical therapy.4,5 CPPS is reportedly as serious as active angina pectoris and myocardial infarction in deteriorating the QoL.5 The National Institutes of Health (NIH) classify prostatitis-like symptoms into four categories: infectious forms (acute and chronic bacterial prostatitis); CPPS; and asymptomatic prostatitis.1 CPPS was classified as NIH category III and accounts for most of the prostatitis-like symptoms in >90% of patients.6 However, the
http://dx.doi.org/10.1016/j.urols.2017.03.006 1879-5226/Copyright © 2017, Taiwan Urological Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
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M.-H. Yang et al. / Urological Science xxx (2017) 1e6
pathophysiology of CPPS is still poorly understood, despite the common occurrence of this disease. Pelvic floor muscle irregularities, neurological dysfunction, chemical irritants, and endocrine and immunological factors all might play a role.7 The management of CPPS is extremely challenging for both clinicians and patients. The mainstay intervention has been a combination of antibiotics, a-blockers, and/or anti-inflammatories,6 but the response rate is limited, at 20e65%.8 However, the symptoms of CPPS are increasingly recognized as having little to do with the prostate, but appear to be more related to chronic spasm and trigger point formation in the pelvic floor muscles.9e12 Many alternative treatments have therefore been investigated, such as electrostimulation (ES) and biofeedback physical therapy applied to the pelvic floor. ES has commonly been used as a neuromodulation therapy and is based on pain desensitization via the ascending pathway and induced muscle-contracting fatigue for subsequent relaxation.13 Biofeedback therapy using a monitoring machine to assist muscular reeducation by maximum muscle contraction prompts maximum muscle relaxation.14,15 Both therapies have been commonly used to treat pelvic floor dysfunctions, such as urinary incontinence16 and pelvic floor dyssynergia.17 Previous studies demonstrated that both ES and biofeedback physical therapy result in positive symptomatic improvement for patients with CPPS who were refractory to medical treatment.14,15,18e20 Pelvic floor electromagnetic stimulation (EMS) has also recently provided a promising new noninvasive and convenient treatment option for male CPPS.18,21 However, no study has yet compared the effects of EMS and electrostimulation plus biofeedback (ESB) as treatments for CPPS. The present study is a retrospective investigation aimed at elucidating the treatment differences between EMS and ESB of the pelvic floor muscle in male patients with refractory CPPS. 2. Materials and methods Between April 2014 and June 2016, we retrieved all records of patients diagnosed with CPPS who had failed to improve their clinical symptoms with medication and had been referred to our urological outpatient department and pelvic rehabilitation center for further management. Postprostatic massage voided bladder urine and expressed prostatic secretion were performed to identify NIH category of prostatitis. Men, who were aged at least 18 years, complained of pain over the perineal, testicular, or penile region with a diagnosis consistent with the NIH category III (IIIA and IIIB), and had been symptomatic for at least 3 months after pharmacotherapy had failed were eligible for inclusion in the study. The diagnosis of CPPS was made according to European Association of Urology guidelines.22 Refractory CPPS was defined as no clinical improvement in the patient's pain perception, regardless of treatment, for at least 3 months. The pharmacotherapy included antibiotic, a-blocker, anti-inflammatory, and neurotrophic agents. A physical examination, urinalysis, microbiologic cultures, uroflowmetry, residual urine, and transrectal ultrasonography of the prostate were performed to exclude infection or other obvious pathologies. The medical history, disease duration of CPPS, and previous treatment history were recorded. Patients who were taking any kind of medication for CPPS before our treatment were encouraged to take the medications without adding new drugs during the intervention period. All ESB and EMS pelvic floor treatments were performed by the same physical therapist (Y.F.L.).
courses were performed twice a week for 2 weeks, and later, once a week for 4 weeks. Each session lasted about 45 minutes and included 15 minutes of biofeedback, followed by 30 minutes of ES. The goal of biofeedback physical therapy was to restore normal control of the contraction and relaxation of the pelvic floor muscles. The physical therapist first performted a pelvic examination through transrectal examination of the pelvic floor, and then prescribed exercise via palpation of the pelvic floor muscles (levator ani muscle, obturator internus muscle, and tissues of the urogenital diaphragm). The biofeedback measurements were then performed to assist the relaxation exercises and improve muscle contraction ability. The biofeedback and ES apparatus (Myomed 932, Enraf-Nonius, Rotterdam, The Netherlands) was a complete unit for electromyography (EMG)-feedback, pressure feedback, electrotherapy, and electro diagnostics. The patient was placed in a supine position with bent legs, and an intra-anal probe (Anuform; Neen, Sutton-inAshfield, Nottinghamshire, UK) was placed in the anal canal to measure the resting tone and EMG activity of the levator ani muscle. Patients were given detailed instructions regarding the correct way to contract and relax the pelvic floor muscles under the guidance of feedback through palpation of the pelvic floor muscles and biofeedback measurements. After biofeedback physical therapy, ES was administered by same intra-anal probe and apparatus. The frequency set was the same as EMS with 10 Hz for the first 15 minutes, followed by 70 Hz for another 15 minutes. 2.2. EMS group In April 2015, our rehabilitation center equipped with electromagnetic chair (BioCon-2000; Mcube Technology, Seoul, Korea). We provided EMS of the pelvic floor muscle for our referred CPPS patients. Patients with lower spine, lower extremity, and pelvis instrumentation were excluded to avoid magnet field interference. EMS was administered for 30 minutes, twice weekly, for 6 weeks. The patients were fully clothed while seated on the electromagnetic chair. The frequency was set low at 10 Hz for the first 15minute period for treating pelvic floor pain and was then increased to 70 Hz for the second 15-minute period for treating musculoskeletal tightness. The intensity was set as tolerated by the patient. 2.3. Follow-up and outcome measurement The validated Taiwan version NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), and visual analogue score (VAS) for pain were used in our clinic. Before the first treatment, each patient was asked to complete the questionnaires under the instruction of a research nurse. All patients were contacted by telephone to acquire post-treatment questionnaire responses by the same nurse 12 weeks after the last treatment. The primary outcome was the between-group difference in total score reduction of the NIH-CPSI from baseline to posttreatment. Based on a previous study,23 a 6-point decline in the NIH-CPSI total score was regarded as significant to predict treatment response. The secondary outcomes included the difference in the subscores of the NIH-CPSI, IPSS, and VAS between the groups from baseline to posttreatment. Any patient who lacked a complete questionnaire record was excluded from our analysis. 2.4. Statistical analysis
2.1. ESB group From April 2014 to March 2015, we treated referred refractory CPPS patients with ESB, applied to the pelvic floor muscle. The
We used the Student t test for comparisons of continuous variables. The Chi-square test was used to compare relationships on categorical variables. Before/after therapeutic effects of EMS and
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
M.-H. Yang et al. / Urological Science xxx (2017) 1e6
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ESB physical therapy groups were compared using a paired Student t test. The independent Student t test was used to determine the differences in the changes from baseline for the NIH-CPSI, IPSS, and VAS scores between EMS and ESB groups. Any p value < 0.05 was considered statistically significant. 3. Results Fifty-six patients were referred for treatment with the diagnosis of CPPS from the urological outpatient clinic. Six patients were excluded due to their history of prostate cancer, epididymitis, or sexually transmitted disease (gonorrhea urethritis). Five patients were excluded due to insufficient post-treatment questionnaire response (three in the EMS and two in the ESB group). A total of 23 patients received EMS, while 22 patients received ESB therapy. The baseline characteristics between the two groups are presented in Table 1. The overall mean age was 44.5 (range, 23e76) years, and the mean disease duration was 25.3 (range, 6e144) months, with no statistical difference between the two groups. The patient baseline disease severity according to the symptom questionnaires, including the NIH-CPSI, IPSS, and VAS, indicated no statistical difference between the two groups (p > 0.05). The NIH-CPSI scores were rated as moderate to severe (range, 15e34 on a scale of 34) for 83% of the patients in the EMS group and for 100% of the patients in the ESB group. All patients tolerated the treatment well, and no adverse effects arose requiring further intervention or discontinuation of the treatment course. Treatment responders were defined and measured by the NIHCPSI as those who experienced a relevant decrease of >6 points.23 We found 19 responders (82.6%) in the EMS group and 22 responders (100%) in the ESB group. Figure 1 and Table 2 show significant reductions in pain, improvement in QoL, and increases in total score of NIH-CPSI in both groups (all p < 0.05). The ESB group Table 1 Patient baseline characteristics of EMS and ESB groups.
Age (y) Disease duration (mo) Prostate size (g) PSA NIH category of prostatitis IIIa IIIb Comorbidity Hypertension Diabetes mellitus Coronary artery disease Erectile dysfunction Overactive bladder Use of pharmacotherapy Analgesic agent a-blocker Gabapentin Bromazepam PDE5 inhibitor Anti-cholinergic Baseline Questionnaires NIH-CPSI Mild (0e14) Moderate (15e29) Severe (30e34) IPSS VAS
EMS (n ¼ 23)
ESB (n ¼ 22)
p
45.6 (23e76) 20.4 (6e72) 25.2 (12e58) 1.6 ± 1.2
43.4 (24e68) 30.4 (6e144) 26.4 (12e40) 1.5 ± 1.0
0.584 0.175 0.701 0.128
7 (30.4) 16 (69.6)
5 (22.7) 17 (77.3)
0.559
2 0 0 2 2
0 2 1 0 1
(0) (9) (5) (0) (5)
0.489 0.233 0.489 0.489 0.577
19 (83) 17 (74) 11 (48) 6 (26) 2 (9) 1 (4)
20 (91) 15 (68) 10 (45) 5 (23) 0 (0) 1 (5)
0.413 0.672 0.873 0.793 0.489 0.974
22.5 ± 8.5 4 (17) 13 (57) 6 (26) 12.5 ± 7.1 5.5 ± 2.6
27.0 ± 7.2 0 (0) 13 (59) 9 (41) 11.6 ± 7.5 5.9 ± 2.2
0.065
(9) (0) (0) (9) (9)
0.684 0.598
Data are presented as n (%), n (range), or mean ± standard deviation. EMS ¼ electromagnetic stimulation; ESB ¼ electrostimulation plus biofeedback physical therapy; IPSS ¼ International Prostate Symptom Score; NIN-CPSI ¼ NIHChronic Prostatitis Symptom Index; PSA ¼ prostate specific antigen; VAS ¼ visual analogue scale.
Figure 1. (A) Reduction in mean NIH-CPSI scores after treatment in the EMS and ESB groups. (B) Mean IPSS score reduction after treatment in the EMS and ESB groups. (C) Mean VAS score reduction after treatment in the EMS and ESB groups. *p < 0.05. EMS ¼ electromagnet stimulation; ESB ¼ electrostimulation plus biofeedback; IPSS ¼ International prostate symptom score; NIH-CPSI ¼ National Institutes of Health Chronic Prostatitis Symptoms Index; QoL ¼ quality of life; VAS ¼ visual analogue scale.
also demonstrated an improvement in the urinary subscore of the NIH-CPSI. No significant differences were noted between the groups in the urinary score measures of the NIH-CPSI. The mean pain score (p ¼ 0.035), QoL score (p ¼ 0.012), and total score (p ¼ 0.009) improved significantly in the ESB group compared with the EMS group. The total IPSS improved significantly after
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
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M.-H. Yang et al. / Urological Science xxx (2017) 1e6
Table 2 Comparison the treatment effects of EMS and ESB groups. EMS
NIH-CPSI Total score Pain score Urinary score QoL score IPSS Total score Storage score Voiding score VAS
ESB pa
Baseline
Post-treatment (12 weeks)
Change
pb
pc
6.9 3.6 2.5 3.5
<0.001 <0.001 0.228 0.001
27.0 ± 7.2 13.0 ± 3.3 4.0 ± 2.7 10.0 ± 2.3
12.7 ± 8.5 4.7 ± 4.1 3.2 ± 1.8 4.8 ± 4.1
14.2 ± 4.8 8.3 ± 3.6 0.7 ± 1.6 5.2 ± 2.8
<0.001 <0.001 0.043 <0.001
0.009 0.035 0.899 0.012
7.6 2.7 6.2 2.3
0.031 0.071 0.06 <0.001
11.6 ± 7.5 5.2 ± 3.0 6.4 ± 5.4 5.9 ± 2.2
7.0 3.8 3.2 2.4
0.004 0.06 0.002 <0.001
0.663 0.725 0.697 0.084
Baseline
Post-treatment (12 weeks)
Change
22.5 ± 8.51 10.8 ± 4.3 3.0 ± 2.9 8.7 ± 2.8
13.2 ± 5.7 4.8 ± 3.7 2.3 ± 1.2 6.0 ± 2.2
9.3 6.0 0.6 2.7
± ± ± ±
12.5 ± 7.1 5.1 ± 2.7 7.4 ± 5.8 5.5 ± 2.6
8.8 4.0 4.8 3.0
± ± ± ±
3.7 1.1 2.6 2.4
± ± ± ±
4.1 1.7 2.7 1.7
± ± ± ±
3.2 1.5 2.5 1.8
4.6 1.4 3.2 3.5
± ± ± ±
6.7 3.3 4.2 1.7
Data are presented as mean ± standard deviation. EMS ¼ electromagnetic stimulation; ESB ¼ electrostimulation plus biofeedback physical therapy; IPSS ¼ International Prostate Symptom Score; NIN-CPSI ¼ NIH-Chronic Prostatitis Symptom Index; PSA ¼ prostate-specific antigen; QoL: quality of life; VAS ¼ visual analogue scale. a Compare before and after treatment of EMS group. b Compare before and after of treatment of ESB group. c Compare normalization amount between EMS and ESB.
treatment in both groups. The ESB group presented with a reduction in the voiding subdomain of IPSS (p ¼ 0.002). However, no significant differences were detected between the groups in terms of the total and subdomain sums of the IPSS. A significant decrease was observed in the VAS for pain in both groups and no differences were evident between the groups. 4. Discussion Our results demonstrate that both EMS and ESB of the pelvic floor muscle are effective in treating refractory CPPS in male patients. Concomitant ES and biofeedback (ESB group) produced a much greater improvement in total, pain, and QoL scores of NIHCPSI when compared with the EMS group. The prostatocentric approach might mislead the treatment direction.15 Increasingly more studies now recommend multimodal therapy according to UPOINT classification with 6-point system, which comprises Urinary symptoms, Psychological dysfunction, Organ-specific symptoms, Infection, Neurologic/systemic conditions, and Tenderness of muscles, as this treatment could maximize the therapeutic effect.24,25 CPPS is defined as pelvic region pain persisting for at least 3 months of the previous 6 months.22 Urinary symptoms and/or sexual dysfunction may also occur. The NIH-CPSI is considered the most reliable outcome parameter measurement of CPPS in primary care.6 This self-finished questionnaire is composed of nine questions in three domains: pain, urinary symptoms, and the impact on QoL.6 In addition, the IPSS and the International Index of Erectile Function also present valuable measures for evaluating the disease response to treatment.6 The diagnosis was made after excluding other pathologies of pelvic pain, including urinary tract infection, cancer, anatomic abnormalities, or neurologic disorders.22 Although the definitive etiology of CPPS remains unclear, bacteria do not appear to play a dominant role.15 Some evidence supports a role for muscular dysfunction and neural inflammation of the pelvic floor.7,11,12 This can lead to a vicious-cycling immunologic inflammatory condition and/or neurogenic injury, predisposing acute and then chronic pain.26 Segura et al9 hypothesized that the etiology of CPPS was similar to that diagnosed as pelvic floor tension myalgia or levator ani syndrome. The tone of the pelvic floor muscles, including short external rotators and levator ani, may play roles in the pathophysiology of CPPS.9 Other evidence supports a role for neurogenic inflammation, peripheral, and then central nervous system sensitization in the maintenance of neuropathic pain perception in
CPPS.7 These hypotheses have been further verified by other trials demonstrating that some patients with CPPS had pathological tenderness and may benefit from pelvic floor physical and neuromodulatory therapies.11,12 EMS generates an electric current in a rapidly changing magnetic field, based on Faraday's principle.21 This treatment induces an eddy current in the tissue by generating a magnetic field that contains the pulse. The clinical efficacy of this extracorporeal magnetic treatment is due to changes in the activity of the pelvic muscles. If the terminal motor nerve fiber is repeatedly activated, the motor end plate tends to be reinforced in terms of force and endurance.27 Thus, normal pelvic muscular activity can be regained by breaking the neural inflammation and the cycle of pelvic muscle spasms. Unlike direct ES, which is subject to poor tissue penetration, EMS is believed to achieve greater tissue depth and a more central effect. In addition, EMS for CPPS treatment might predispose specific pain imprints in the brain.7 EMS is currently used as a noninvasive alternative for patients who refuse intra-anal therapy during ES. The patient may sit down on the treatment chair while fully clothed, and the electric current is induced in the pelvic floor by changing the magnetic field. The magnetic waves penetrate the pelvic floor and locally stimulate the muscles by activating the nerves. The effect seems to involve the motor, as well as the sensory fibers of the pelvic floor innervations.19 Rowe et al18 conducted EMS therapy for CPPS consisting of 15 minutes of pelvic floor stimulation at a frequency of 10 Hz, followed by a further 15 minutes at 50 Hz, twice weekly for 4 weeks. The mitigation of pain and urinary symptoms was still evident even 1 year after EMS treatment. Subgroup analysis of patients undergoing active treatment showed that the greatest improvement was in pain-related symptoms.18 Kim et al19 reported that EMS offers a new treatment option for patients with CPPS who do not respond to pharmacotherapy. Patients presented with improvement in total and pain subdomain score of NIH-CPSI with a maintenance of the effect for 24 weeks.19 Our short-term (12 weeks) EMS treatment follow-up gave the same results, where the pain score was the mainstay of improvement, as reported previously. However, our urinary score did not decrease after EMS treatment, contrary to the findings of Kim et al.19 The differences in baseline urinary scores (8.6 in Kim et al's study19 vs. 3.0 in our report) may possibly explain this discrepancy. Biofeedback is frequently recommended as a treatment for CPPS, based on the principle that maximum muscle contraction promotes maximum muscle relaxation. Consequently, the
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
M.-H. Yang et al. / Urological Science xxx (2017) 1e6
relaxation phase is a mediative state between muscle contractions.14 Nadler28 reported some improvements in the NIH-CPSI scores of eight out of 11 patients with CPPS treated by this method. Pelvic floor ES was believed to work through the pudendal efferents and afferents.13 Two theories are proposed to explain the efficacy of ES: one is that it alters the perception of pain by introducing exogenous electricity to change the native electrical signals of the nervous system, the other is that muscle stimulation to the fatigue level breaks the cycle of muscular spasm.13 High frequency electrical stimulation of afferent nerve fibers is also hypothesized to control visceral pain by restoring pain transmission from C-fibers to A-d fibers.29 ES and biofeedback of the pelvic floor muscle were treatment indicators and showed acceptable therapeutic effects in refractory CPPS.13e15,18e20 Biofeedback and the ES apparatus (Myomed 932; Enraf-Nonius) were set up as a complete unit for EMG feedback, pressure feedback, electrotherapy, and electro diagnostics in our pelvic rehabilitation center. We have treated referred CPPS patients with simultaneous ES and biofeedback for the past 5 years. The ESB group demonstrated significant improvement in all scores in the NIH-CPSI and even in the voiding subdomain in the IPSS. The excellent results reported previously for bladder-sphincter pseudodyssynergia treatment in response to both ES and biofeedback10 may possibly explain the synergistic effects observed in the ESB group. Concomitant treatments may promote more coordinated bladder and sphincter activity, which may then contribute to alleviating bladder outlet resistance. These effects may partly explain why our ESB group showed improvement in the voiding rather than the storage domain. Perception of pain signal, no matter what its origin, can lead to both reflex and voluntary muscle contraction, which may cause more pain and dysfunction. All clinicians agree that all CPPS patients have some degree of chronic tenderness and tension in pelvic floor muscle, which contributes significantly to the pain. Previous research had reported that the pain degree was the most robust predictor of a poorer QoL.5 In the present retrospective study in men with CPPS refractory to medical treatment, both pelvic floor EMS and ESB treatment were able to relieve the pain (core symptoms of CPPS), and this improved the QOL domain. According to the gate control theory, there is a gateway in the dorsal horn of the spinal cord controlling and/or regulating the flow of nociceptive information. If appropriately stimulated, it may result in a reduction of pain perception.30 Neuromodulative techniques, based on the theory of pain sensitization via descending and ascending pathways, have become increasingly popular for treating chronic pain, and have had promising results.31,32 ES and EMS are types of neuromodulation, which can exert its pain-relieving effects at a number of points along the reflex pathways by: (1) affecting the types of signals being transmitted via the afferent nerves20; (2) altering the processing of afferent signals within the brain circuitry20; (3) altering the efferent signals to the bladder or pelvic floor13; or (4) recruiting a larger number of nerve fibers due to a wider activation of inhibitory interneurons,33 which then mitigates the pelvic pain. Our results suggested that slightly better effects in pain relief, QoL improvement, and subsequent total scores in CPSI were obtained with ESB than with EMS when treating refractory CPPS. We postulate that biofeedback in the ESB treatment, by guiding the identification of tight pelvic floor muscles and then training the patient to relax these muscles, may provide further help in relieving the uncomfortable conditions caused by CPPS. Animal and human studies have shown that adequate and sufficient muscle exercise diminishes the pain experience by its effect on the endogenous pain modulatory systems.34 The mechanism of the biofeedback-oriented muscle exercise was suggested to involve the promotion of b-endorphin release.35 Theoretically, ESB would
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be more suitable for patients with pelvic muscle tenderness or signs of neurologic system abnormality. We found that tenderness and tension of the pelvic floor musculature, including associated tissues, were commonly palpable during digital examination of our patients. Biofeedback in ESB may direct and educate patients with CPPS to strengthen their pelvic floor muscles.14 Improved pelvic muscle health, in turn, may result in less spasm and pain. In summary, ESB provokes increases in pelvic floor muscle redirection and decreases in bladder outlet resistance, which could be the key to why it outweighs EMS as a short-term CPPS treatment in our study.10 Some limitations to our study need to be mentioned. First, it is a retrospective, nonrandomized, single-center study on a limited group of patients, which probably created bias. Larger prospective controlled studies are still required to establish the overall generalization of the findings of this comparison study. Second, urinary symptoms were rated only by questionnaires. Additional urodynamic studies, perhaps including uroflowmetry, may increase the persuasiveness of the voiding improvement. Third, our follow-up period was only 12 weeks after completion of treatment, so longterm results may be valuable to validate our findings. Finally, the question remains of whether the treatment intensity of our biofeedback-directed exercise of the pelvic floor muscle could provoke b-endorphin release for pain relief. The answer remains elusive and requires further study. 5. Conclusion Both EMS and ESB physical therapy applied to the pelvic floor muscle are effective for pain reduction, increased QoL, and improvement of lower urinary tract symptoms in male CPPS patients who are refractory to medical treatments. The combination therapies of ES plus biofeedback demonstrate additional benefit in pain reduction and QoL when compared with EMS alone. Conflicts of interest The authors have no conflicts of interest to declare. References 1. Krieger JN, Nyberg Jr L, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282:236e7. 2. Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. Int J Antimicrob Agents 2008;31(Suppl 1):S85e90. 3. Nickel JC, Teichman JM, Gregoire M, Clark J, Downey J. Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial cystitis, and epididymitis in outpatient urological practice: the Canadian PIE Study. Urology 2005;66:935e40. 4. Nickel JC, Downey JA, Nickel KR, Clark JM. Prostatitis-like symptoms: one year later. BJU Int 2002;90:678e81. 5. Wenninger K, Heiman JR, Rothman I, Berghuis JP, Berger RE. Sickness impact of chronic nonbacterial prostatitis and its correlates. J Urol 1996;155:965e8. 6. Magistro G, Wagenlehner FM, Grabe M, Weidner W, Stief CG, Nickel JC. Contemporary management of chronic prostatitis/chronic pelvic pain syndrome. Eur Urol 2016;69:286e97. 7. Pontari MA, Ruggieri MR. Mechanisms in prostatitis/chronic pelvic pain syndrome. J Urol 2008;179(5 Suppl):S61e7. 8. Anothaisintawee T, Attia J, Nickel JC, Thammakraisorn S, Numthavaj P, McEvoy M, et al. Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis. JAMA 2011;305: 78e86. 9. Segura JW, Opitz JL, Greene LF. Prostatosis, prostatitis or pelvic floor tension myalgia? J Urol 1979;122:168e9. 10. Kaplan SA, Santarosa RP, D'Alisera PM, Fay BJ, Ikeguchi EF, Hendricks J, et al. Pseudodyssynergia (contraction of the external sphincter during voiding) misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a therapeutic option. J Urol 1997;157:2234e7. 11. Zermann DH, Ishigooka M, Doggweiler R, Schmidt RA. Neurourological insights into the etiology of genitourinary pain in men. J Urol 1999;161:903e8.
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
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12. Hetrick DC, Ciol MA, Rothman I, Turner JA, Frest M, Berger RE. Musculoskeletal dysfunction in men with chronic pelvic pain syndrome type III: a caseecontrol study. J Urol 2003;170:828e31. 13. Yang CC. Neuromodulation in male chronic pelvic pain syndrome: rationale and practice. World J Urol 2013;31:767e72. 14. Clemens JQ, Nadler RB, Schaeffer AJ, Belani J, Albaugh J, Bushman W. Biofeedback, pelvic floor re-education, and bladder training for male chronic pelvic pain syndrome. Urology 2000;56:951e5. 15. Cornel EB, van Haarst EP, Schaarsberg RW, Geels J. The effect of biofeedback physical therapy in men with chronic pelvic pain syndrome type III. Eur Urol 2005;47:607e11. 16. Richmond CF, Martin DK, Yip SO, Dick MA, Erekson EA. Effect of supervised pelvic floor biofeedback and electrical stimulation in women with mixed and stress urinary incontinence. Female Pelvic Med Reconstr Surg 2016;22:324e7. 17. Cadeddu F, Salis F, De Luca E, Ciangola I, Milito G. Efficacy of biofeedback plus transanal stimulation in the management of pelvic floor dyssynergia: a randomized trial. Tech Coloproctol 2015;19:333e8. 18. Rowe E, Smith C, Laverick L, Elkabir J, Witherow RO, Patel A. A prospective, randomized, placebo controlled, double-blind study of pelvic electromagnetic therapy for the treatment of chronic pelvic pain syndrome with 1 year of follow up. J Urol 2005;173:2044e7. 19. Kim TH, Han DH, Cho WJ, Lee HS, You HW, Park CM, et al. The efficacy of extracorporeal magnetic stimulation for treatment of chronic prostatitis/ chronic pelvic pain syndrome patients who do not respond to pharmacotherapy. Urology 2013;82:894e8. 20. Kessler TM, Mordasini L, Weisstanner C, Jüni P, da Costa BR, Wiest R, et al. Sonoelectro-magnetic therapy for treating chronic pelvic pain syndrome in men: a randomized, placebo-controlled, double-blind trial. PLoS One 2014;9:e113368. 21. Gilling PJ, Wilson LC, Westenberg AM, McAllister WJ, Kennett KM, Frampton CM, et al. A double-blind randomized controlled trial of electromagnetic stimulation of the pelvic floor vs sham therapy in the treatment of women with stress urinary incontinence. BJU Int 2009;103:1386e90. 22. Fall M, Baranowski AP, Elneil S, Engeler D, Hughes J, Messelink EJ, et al. EAU guidelines on chronic pelvic pain. Eur Urol 2010;57:35e48.
23. Propert KJ, Litwin MS, Wang Y, Alexander RB, Calhoun E, Nickel JC, et al. Responsiveness of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). Qual Life Res 2006;15:299e305. 24. Magri V, Wagenlehner F, Perletti G, Schneider S, Marras E, Naber KG, et al. Use of the UPOINT chronic prostatitis/chronic pelvic pain syndrome classification in European patient cohorts: sexual function domain improves correlations. J Urol 2010;184:2339e45. 25. Shoskes DA, Nickel JC, Kattan MW. Phenotypically directed multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome: a prospective study using UPOINT. Urology 2010;75:1249e53. 26. Curtis Nickel J, Baranowski AP, Pontari M, Berger RE, Tripp DA. Management of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome who have failed traditional management. Rev Urol 2007;9:63e72. 27. Galloway NT, El-Galley RE, Sand PK, Appell RA, Russell HW, Carlin SJ. Update on extracorporeal magnetic innervation (EXMI) therapy for stress urinary incontinence. Urology 2000;56(6 Suppl 1):82e6. 28. Nadler RB. Bladder training biofeedback and pelvic floor myalgia. Urology 2002;60(6 Suppl):42e3. discussion 44. 29. John H, Ruedi C, Kotting S, Schmid DM, Fatzer M, Hauri D. A new high frequency electrostimulation device to treat chronic prostatitis. J Urol 2003;170(4 Pt 1):1275e7. 30. Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971e9. 31. Vallejo R, Kramer J, Benyamin R. Neuromodulation of the cervical spinal cord in the treatment of chronic intractable neck and upper extremity pain: a case series and review of the literature. Pain Physician 2007;10:305e11. 32. Nnoaham KE, Kumbang J. Transcutaneous electrical nerve stimulation (TENS) for chronic pain. Cochrane Database Syst Rev 2008;3:Cd003222. 33. Kothari S. Neuromodulatory approaches to chronic pelvic pain and coccygodynia. Acta Neurochir Suppl 2007;97:365e71. 34. Kroll HR. Exercise therapy for chronic pain. Phys Med Rehabil Clin N Am 2015;26:263e81. 35. Goldfarb AH, Jamurtas AZ. Beta-endorphin response to exercise. An update. Sports Med 1997;24:8e16.
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
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Original article
Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome Min-Hsin Yang a, b, Yu-Hui Huang c, d, Yu-Fen Lai e, Sheng-Wei Zeng c, Sung-Lang Chen a, d, * a
Department of Urology, Chung Shan Medical University Hospital, Taichung, Taiwan Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan d School of Medicine, Chung Shan Medical University, Taichung, Taiwan e Department of Physical Therapy, Chung Shan Medical University Hospital, Taichung, Taiwan b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 December 2016 Received in revised form 17 February 2017 Accepted 21 March 2017 Available online xxx
Objective: The aim of this study was to compare the effectiveness of electromagnetic stimulation (EMS) versus electrostimulation plus biofeedback (ESB) for the treatment of refractory chronic pelvic pain syndrome (CPPS) in men. Materials and Methods: A total of 23 male refractory CPPS patients were included in the study. EMS was applied for 30 minutes, three times weekly, for 6 weeks, for pelvic floor rehabilitation. We retrospectively compared the outcomes with 22 male refractory CPPS patients treated with ESB twice a week for 2 weeks, and later once a week for 4 weeks. Each ESB session lasted 45 minutes, including biofeedback (15 minutes) followed by electrostimulation (30 minutes). The outcome measures included the National Institutes of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), International Prostate Symptom Score (IPSS), and a visual analogue score for pain from baseline to 12 weeks after completion of treatment. Results: Significantly reduced pain, improved quality of life (QoL), and lowered total score of the NIHCPSI were observed in both groups (all p < 0.05). The ESB group also demonstrated improvement in the urinary subscore of the NIH-CPSI. No significant differences were found between the groups in the urinary score measures of the NIH-CPSI. The mean pain score (p ¼ 0.035), QoL (p ¼ 0.012), and total score (p ¼ 0.009) improved significantly in the ESB group compared with EMS group. Total IPSS and visual analogue score improved significantly after treatment in both groups. However, no significant differences were noted between the groups in the total and subdomain sums of the IPSS. Conclusion: Both EMS and ESB physical therapy of the pelvic floor muscle effectively reduce pain, increase the QoL, and improve urinary tract symptoms in male CPPS patients who are refractory to medical treatments. The combination therapy of ES plus biofeedback demonstrates additional benefits in pain and QoL when compared with EMS alone. Copyright © 2017, Taiwan Urological Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: chronic pelvic pain syndrome chronic prostatitis electromagnetic stimulation electrostimulation biofeedback
1. Introduction Chronic pelvic pain syndrome (CPPS) is a bothersome condition with a main manifestation represented by pelvic region pain, with or without lower urinary tract symptoms, lasting >3 months in the absence of infection or other obvious pathology.1 It presents as prostatitis-like symptoms and affects around 2.2e9.7% of male
* Corresponding author. Department of Urology, Chung-Shan Medical University Hospital, 110 Chien-Kuo North Road, Section 1, Taichung 402, Taiwan E-mail address: [email protected] (S.-L. Chen).
patients and accounts for about 3% of male outpatient visits.2,3 The negative impact on quality of life (QoL) is enormous, as approximately one third of these patients experience a relapse of symptoms a year or more after medical therapy.4,5 CPPS is reportedly as serious as active angina pectoris and myocardial infarction in deteriorating the QoL.5 The National Institutes of Health (NIH) classify prostatitis-like symptoms into four categories: infectious forms (acute and chronic bacterial prostatitis); CPPS; and asymptomatic prostatitis.1 CPPS was classified as NIH category III and accounts for most of the prostatitis-like symptoms in >90% of patients.6 However, the
http://dx.doi.org/10.1016/j.urols.2017.03.006 1879-5226/Copyright © 2017, Taiwan Urological Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
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pathophysiology of CPPS is still poorly understood, despite the common occurrence of this disease. Pelvic floor muscle irregularities, neurological dysfunction, chemical irritants, and endocrine and immunological factors all might play a role.7 The management of CPPS is extremely challenging for both clinicians and patients. The mainstay intervention has been a combination of antibiotics, a-blockers, and/or anti-inflammatories,6 but the response rate is limited, at 20e65%.8 However, the symptoms of CPPS are increasingly recognized as having little to do with the prostate, but appear to be more related to chronic spasm and trigger point formation in the pelvic floor muscles.9e12 Many alternative treatments have therefore been investigated, such as electrostimulation (ES) and biofeedback physical therapy applied to the pelvic floor. ES has commonly been used as a neuromodulation therapy and is based on pain desensitization via the ascending pathway and induced muscle-contracting fatigue for subsequent relaxation.13 Biofeedback therapy using a monitoring machine to assist muscular reeducation by maximum muscle contraction prompts maximum muscle relaxation.14,15 Both therapies have been commonly used to treat pelvic floor dysfunctions, such as urinary incontinence16 and pelvic floor dyssynergia.17 Previous studies demonstrated that both ES and biofeedback physical therapy result in positive symptomatic improvement for patients with CPPS who were refractory to medical treatment.14,15,18e20 Pelvic floor electromagnetic stimulation (EMS) has also recently provided a promising new noninvasive and convenient treatment option for male CPPS.18,21 However, no study has yet compared the effects of EMS and electrostimulation plus biofeedback (ESB) as treatments for CPPS. The present study is a retrospective investigation aimed at elucidating the treatment differences between EMS and ESB of the pelvic floor muscle in male patients with refractory CPPS. 2. Materials and methods Between April 2014 and June 2016, we retrieved all records of patients diagnosed with CPPS who had failed to improve their clinical symptoms with medication and had been referred to our urological outpatient department and pelvic rehabilitation center for further management. Postprostatic massage voided bladder urine and expressed prostatic secretion were performed to identify NIH category of prostatitis. Men, who were aged at least 18 years, complained of pain over the perineal, testicular, or penile region with a diagnosis consistent with the NIH category III (IIIA and IIIB), and had been symptomatic for at least 3 months after pharmacotherapy had failed were eligible for inclusion in the study. The diagnosis of CPPS was made according to European Association of Urology guidelines.22 Refractory CPPS was defined as no clinical improvement in the patient's pain perception, regardless of treatment, for at least 3 months. The pharmacotherapy included antibiotic, a-blocker, anti-inflammatory, and neurotrophic agents. A physical examination, urinalysis, microbiologic cultures, uroflowmetry, residual urine, and transrectal ultrasonography of the prostate were performed to exclude infection or other obvious pathologies. The medical history, disease duration of CPPS, and previous treatment history were recorded. Patients who were taking any kind of medication for CPPS before our treatment were encouraged to take the medications without adding new drugs during the intervention period. All ESB and EMS pelvic floor treatments were performed by the same physical therapist (Y.F.L.).
courses were performed twice a week for 2 weeks, and later, once a week for 4 weeks. Each session lasted about 45 minutes and included 15 minutes of biofeedback, followed by 30 minutes of ES. The goal of biofeedback physical therapy was to restore normal control of the contraction and relaxation of the pelvic floor muscles. The physical therapist first performted a pelvic examination through transrectal examination of the pelvic floor, and then prescribed exercise via palpation of the pelvic floor muscles (levator ani muscle, obturator internus muscle, and tissues of the urogenital diaphragm). The biofeedback measurements were then performed to assist the relaxation exercises and improve muscle contraction ability. The biofeedback and ES apparatus (Myomed 932, Enraf-Nonius, Rotterdam, The Netherlands) was a complete unit for electromyography (EMG)-feedback, pressure feedback, electrotherapy, and electro diagnostics. The patient was placed in a supine position with bent legs, and an intra-anal probe (Anuform; Neen, Sutton-inAshfield, Nottinghamshire, UK) was placed in the anal canal to measure the resting tone and EMG activity of the levator ani muscle. Patients were given detailed instructions regarding the correct way to contract and relax the pelvic floor muscles under the guidance of feedback through palpation of the pelvic floor muscles and biofeedback measurements. After biofeedback physical therapy, ES was administered by same intra-anal probe and apparatus. The frequency set was the same as EMS with 10 Hz for the first 15 minutes, followed by 70 Hz for another 15 minutes. 2.2. EMS group In April 2015, our rehabilitation center equipped with electromagnetic chair (BioCon-2000; Mcube Technology, Seoul, Korea). We provided EMS of the pelvic floor muscle for our referred CPPS patients. Patients with lower spine, lower extremity, and pelvis instrumentation were excluded to avoid magnet field interference. EMS was administered for 30 minutes, twice weekly, for 6 weeks. The patients were fully clothed while seated on the electromagnetic chair. The frequency was set low at 10 Hz for the first 15minute period for treating pelvic floor pain and was then increased to 70 Hz for the second 15-minute period for treating musculoskeletal tightness. The intensity was set as tolerated by the patient. 2.3. Follow-up and outcome measurement The validated Taiwan version NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), and visual analogue score (VAS) for pain were used in our clinic. Before the first treatment, each patient was asked to complete the questionnaires under the instruction of a research nurse. All patients were contacted by telephone to acquire post-treatment questionnaire responses by the same nurse 12 weeks after the last treatment. The primary outcome was the between-group difference in total score reduction of the NIH-CPSI from baseline to posttreatment. Based on a previous study,23 a 6-point decline in the NIH-CPSI total score was regarded as significant to predict treatment response. The secondary outcomes included the difference in the subscores of the NIH-CPSI, IPSS, and VAS between the groups from baseline to posttreatment. Any patient who lacked a complete questionnaire record was excluded from our analysis. 2.4. Statistical analysis
2.1. ESB group From April 2014 to March 2015, we treated referred refractory CPPS patients with ESB, applied to the pelvic floor muscle. The
We used the Student t test for comparisons of continuous variables. The Chi-square test was used to compare relationships on categorical variables. Before/after therapeutic effects of EMS and
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
M.-H. Yang et al. / Urological Science xxx (2017) 1e6
3
ESB physical therapy groups were compared using a paired Student t test. The independent Student t test was used to determine the differences in the changes from baseline for the NIH-CPSI, IPSS, and VAS scores between EMS and ESB groups. Any p value < 0.05 was considered statistically significant. 3. Results Fifty-six patients were referred for treatment with the diagnosis of CPPS from the urological outpatient clinic. Six patients were excluded due to their history of prostate cancer, epididymitis, or sexually transmitted disease (gonorrhea urethritis). Five patients were excluded due to insufficient post-treatment questionnaire response (three in the EMS and two in the ESB group). A total of 23 patients received EMS, while 22 patients received ESB therapy. The baseline characteristics between the two groups are presented in Table 1. The overall mean age was 44.5 (range, 23e76) years, and the mean disease duration was 25.3 (range, 6e144) months, with no statistical difference between the two groups. The patient baseline disease severity according to the symptom questionnaires, including the NIH-CPSI, IPSS, and VAS, indicated no statistical difference between the two groups (p > 0.05). The NIH-CPSI scores were rated as moderate to severe (range, 15e34 on a scale of 34) for 83% of the patients in the EMS group and for 100% of the patients in the ESB group. All patients tolerated the treatment well, and no adverse effects arose requiring further intervention or discontinuation of the treatment course. Treatment responders were defined and measured by the NIHCPSI as those who experienced a relevant decrease of >6 points.23 We found 19 responders (82.6%) in the EMS group and 22 responders (100%) in the ESB group. Figure 1 and Table 2 show significant reductions in pain, improvement in QoL, and increases in total score of NIH-CPSI in both groups (all p < 0.05). The ESB group Table 1 Patient baseline characteristics of EMS and ESB groups.
Age (y) Disease duration (mo) Prostate size (g) PSA NIH category of prostatitis IIIa IIIb Comorbidity Hypertension Diabetes mellitus Coronary artery disease Erectile dysfunction Overactive bladder Use of pharmacotherapy Analgesic agent a-blocker Gabapentin Bromazepam PDE5 inhibitor Anti-cholinergic Baseline Questionnaires NIH-CPSI Mild (0e14) Moderate (15e29) Severe (30e34) IPSS VAS
EMS (n ¼ 23)
ESB (n ¼ 22)
p
45.6 (23e76) 20.4 (6e72) 25.2 (12e58) 1.6 ± 1.2
43.4 (24e68) 30.4 (6e144) 26.4 (12e40) 1.5 ± 1.0
0.584 0.175 0.701 0.128
7 (30.4) 16 (69.6)
5 (22.7) 17 (77.3)
0.559
2 0 0 2 2
0 2 1 0 1
(0) (9) (5) (0) (5)
0.489 0.233 0.489 0.489 0.577
19 (83) 17 (74) 11 (48) 6 (26) 2 (9) 1 (4)
20 (91) 15 (68) 10 (45) 5 (23) 0 (0) 1 (5)
0.413 0.672 0.873 0.793 0.489 0.974
22.5 ± 8.5 4 (17) 13 (57) 6 (26) 12.5 ± 7.1 5.5 ± 2.6
27.0 ± 7.2 0 (0) 13 (59) 9 (41) 11.6 ± 7.5 5.9 ± 2.2
0.065
(9) (0) (0) (9) (9)
0.684 0.598
Data are presented as n (%), n (range), or mean ± standard deviation. EMS ¼ electromagnetic stimulation; ESB ¼ electrostimulation plus biofeedback physical therapy; IPSS ¼ International Prostate Symptom Score; NIN-CPSI ¼ NIHChronic Prostatitis Symptom Index; PSA ¼ prostate specific antigen; VAS ¼ visual analogue scale.
Figure 1. (A) Reduction in mean NIH-CPSI scores after treatment in the EMS and ESB groups. (B) Mean IPSS score reduction after treatment in the EMS and ESB groups. (C) Mean VAS score reduction after treatment in the EMS and ESB groups. *p < 0.05. EMS ¼ electromagnet stimulation; ESB ¼ electrostimulation plus biofeedback; IPSS ¼ International prostate symptom score; NIH-CPSI ¼ National Institutes of Health Chronic Prostatitis Symptoms Index; QoL ¼ quality of life; VAS ¼ visual analogue scale.
also demonstrated an improvement in the urinary subscore of the NIH-CPSI. No significant differences were noted between the groups in the urinary score measures of the NIH-CPSI. The mean pain score (p ¼ 0.035), QoL score (p ¼ 0.012), and total score (p ¼ 0.009) improved significantly in the ESB group compared with the EMS group. The total IPSS improved significantly after
Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006
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Table 2 Comparison the treatment effects of EMS and ESB groups. EMS
NIH-CPSI Total score Pain score Urinary score QoL score IPSS Total score Storage score Voiding score VAS
ESB pa
Baseline
Post-treatment (12 weeks)
Change
pb
pc
6.9 3.6 2.5 3.5
<0.001 <0.001 0.228 0.001
27.0 ± 7.2 13.0 ± 3.3 4.0 ± 2.7 10.0 ± 2.3
12.7 ± 8.5 4.7 ± 4.1 3.2 ± 1.8 4.8 ± 4.1
14.2 ± 4.8 8.3 ± 3.6 0.7 ± 1.6 5.2 ± 2.8
<0.001 <0.001 0.043 <0.001
0.009 0.035 0.899 0.012
7.6 2.7 6.2 2.3
0.031 0.071 0.06 <0.001
11.6 ± 7.5 5.2 ± 3.0 6.4 ± 5.4 5.9 ± 2.2
7.0 3.8 3.2 2.4
0.004 0.06 0.002 <0.001
0.663 0.725 0.697 0.084
Baseline
Post-treatment (12 weeks)
Change
22.5 ± 8.51 10.8 ± 4.3 3.0 ± 2.9 8.7 ± 2.8
13.2 ± 5.7 4.8 ± 3.7 2.3 ± 1.2 6.0 ± 2.2
9.3 6.0 0.6 2.7
± ± ± ±
12.5 ± 7.1 5.1 ± 2.7 7.4 ± 5.8 5.5 ± 2.6
8.8 4.0 4.8 3.0
± ± ± ±
3.7 1.1 2.6 2.4
± ± ± ±
4.1 1.7 2.7 1.7
± ± ± ±
3.2 1.5 2.5 1.8
4.6 1.4 3.2 3.5
± ± ± ±
6.7 3.3 4.2 1.7
Data are presented as mean ± standard deviation. EMS ¼ electromagnetic stimulation; ESB ¼ electrostimulation plus biofeedback physical therapy; IPSS ¼ International Prostate Symptom Score; NIN-CPSI ¼ NIH-Chronic Prostatitis Symptom Index; PSA ¼ prostate-specific antigen; QoL: quality of life; VAS ¼ visual analogue scale. a Compare before and after treatment of EMS group. b Compare before and after of treatment of ESB group. c Compare normalization amount between EMS and ESB.
treatment in both groups. The ESB group presented with a reduction in the voiding subdomain of IPSS (p ¼ 0.002). However, no significant differences were detected between the groups in terms of the total and subdomain sums of the IPSS. A significant decrease was observed in the VAS for pain in both groups and no differences were evident between the groups. 4. Discussion Our results demonstrate that both EMS and ESB of the pelvic floor muscle are effective in treating refractory CPPS in male patients. Concomitant ES and biofeedback (ESB group) produced a much greater improvement in total, pain, and QoL scores of NIHCPSI when compared with the EMS group. The prostatocentric approach might mislead the treatment direction.15 Increasingly more studies now recommend multimodal therapy according to UPOINT classification with 6-point system, which comprises Urinary symptoms, Psychological dysfunction, Organ-specific symptoms, Infection, Neurologic/systemic conditions, and Tenderness of muscles, as this treatment could maximize the therapeutic effect.24,25 CPPS is defined as pelvic region pain persisting for at least 3 months of the previous 6 months.22 Urinary symptoms and/or sexual dysfunction may also occur. The NIH-CPSI is considered the most reliable outcome parameter measurement of CPPS in primary care.6 This self-finished questionnaire is composed of nine questions in three domains: pain, urinary symptoms, and the impact on QoL.6 In addition, the IPSS and the International Index of Erectile Function also present valuable measures for evaluating the disease response to treatment.6 The diagnosis was made after excluding other pathologies of pelvic pain, including urinary tract infection, cancer, anatomic abnormalities, or neurologic disorders.22 Although the definitive etiology of CPPS remains unclear, bacteria do not appear to play a dominant role.15 Some evidence supports a role for muscular dysfunction and neural inflammation of the pelvic floor.7,11,12 This can lead to a vicious-cycling immunologic inflammatory condition and/or neurogenic injury, predisposing acute and then chronic pain.26 Segura et al9 hypothesized that the etiology of CPPS was similar to that diagnosed as pelvic floor tension myalgia or levator ani syndrome. The tone of the pelvic floor muscles, including short external rotators and levator ani, may play roles in the pathophysiology of CPPS.9 Other evidence supports a role for neurogenic inflammation, peripheral, and then central nervous system sensitization in the maintenance of neuropathic pain perception in
CPPS.7 These hypotheses have been further verified by other trials demonstrating that some patients with CPPS had pathological tenderness and may benefit from pelvic floor physical and neuromodulatory therapies.11,12 EMS generates an electric current in a rapidly changing magnetic field, based on Faraday's principle.21 This treatment induces an eddy current in the tissue by generating a magnetic field that contains the pulse. The clinical efficacy of this extracorporeal magnetic treatment is due to changes in the activity of the pelvic muscles. If the terminal motor nerve fiber is repeatedly activated, the motor end plate tends to be reinforced in terms of force and endurance.27 Thus, normal pelvic muscular activity can be regained by breaking the neural inflammation and the cycle of pelvic muscle spasms. Unlike direct ES, which is subject to poor tissue penetration, EMS is believed to achieve greater tissue depth and a more central effect. In addition, EMS for CPPS treatment might predispose specific pain imprints in the brain.7 EMS is currently used as a noninvasive alternative for patients who refuse intra-anal therapy during ES. The patient may sit down on the treatment chair while fully clothed, and the electric current is induced in the pelvic floor by changing the magnetic field. The magnetic waves penetrate the pelvic floor and locally stimulate the muscles by activating the nerves. The effect seems to involve the motor, as well as the sensory fibers of the pelvic floor innervations.19 Rowe et al18 conducted EMS therapy for CPPS consisting of 15 minutes of pelvic floor stimulation at a frequency of 10 Hz, followed by a further 15 minutes at 50 Hz, twice weekly for 4 weeks. The mitigation of pain and urinary symptoms was still evident even 1 year after EMS treatment. Subgroup analysis of patients undergoing active treatment showed that the greatest improvement was in pain-related symptoms.18 Kim et al19 reported that EMS offers a new treatment option for patients with CPPS who do not respond to pharmacotherapy. Patients presented with improvement in total and pain subdomain score of NIH-CPSI with a maintenance of the effect for 24 weeks.19 Our short-term (12 weeks) EMS treatment follow-up gave the same results, where the pain score was the mainstay of improvement, as reported previously. However, our urinary score did not decrease after EMS treatment, contrary to the findings of Kim et al.19 The differences in baseline urinary scores (8.6 in Kim et al's study19 vs. 3.0 in our report) may possibly explain this discrepancy. Biofeedback is frequently recommended as a treatment for CPPS, based on the principle that maximum muscle contraction promotes maximum muscle relaxation. Consequently, the
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M.-H. Yang et al. / Urological Science xxx (2017) 1e6
relaxation phase is a mediative state between muscle contractions.14 Nadler28 reported some improvements in the NIH-CPSI scores of eight out of 11 patients with CPPS treated by this method. Pelvic floor ES was believed to work through the pudendal efferents and afferents.13 Two theories are proposed to explain the efficacy of ES: one is that it alters the perception of pain by introducing exogenous electricity to change the native electrical signals of the nervous system, the other is that muscle stimulation to the fatigue level breaks the cycle of muscular spasm.13 High frequency electrical stimulation of afferent nerve fibers is also hypothesized to control visceral pain by restoring pain transmission from C-fibers to A-d fibers.29 ES and biofeedback of the pelvic floor muscle were treatment indicators and showed acceptable therapeutic effects in refractory CPPS.13e15,18e20 Biofeedback and the ES apparatus (Myomed 932; Enraf-Nonius) were set up as a complete unit for EMG feedback, pressure feedback, electrotherapy, and electro diagnostics in our pelvic rehabilitation center. We have treated referred CPPS patients with simultaneous ES and biofeedback for the past 5 years. The ESB group demonstrated significant improvement in all scores in the NIH-CPSI and even in the voiding subdomain in the IPSS. The excellent results reported previously for bladder-sphincter pseudodyssynergia treatment in response to both ES and biofeedback10 may possibly explain the synergistic effects observed in the ESB group. Concomitant treatments may promote more coordinated bladder and sphincter activity, which may then contribute to alleviating bladder outlet resistance. These effects may partly explain why our ESB group showed improvement in the voiding rather than the storage domain. Perception of pain signal, no matter what its origin, can lead to both reflex and voluntary muscle contraction, which may cause more pain and dysfunction. All clinicians agree that all CPPS patients have some degree of chronic tenderness and tension in pelvic floor muscle, which contributes significantly to the pain. Previous research had reported that the pain degree was the most robust predictor of a poorer QoL.5 In the present retrospective study in men with CPPS refractory to medical treatment, both pelvic floor EMS and ESB treatment were able to relieve the pain (core symptoms of CPPS), and this improved the QOL domain. According to the gate control theory, there is a gateway in the dorsal horn of the spinal cord controlling and/or regulating the flow of nociceptive information. If appropriately stimulated, it may result in a reduction of pain perception.30 Neuromodulative techniques, based on the theory of pain sensitization via descending and ascending pathways, have become increasingly popular for treating chronic pain, and have had promising results.31,32 ES and EMS are types of neuromodulation, which can exert its pain-relieving effects at a number of points along the reflex pathways by: (1) affecting the types of signals being transmitted via the afferent nerves20; (2) altering the processing of afferent signals within the brain circuitry20; (3) altering the efferent signals to the bladder or pelvic floor13; or (4) recruiting a larger number of nerve fibers due to a wider activation of inhibitory interneurons,33 which then mitigates the pelvic pain. Our results suggested that slightly better effects in pain relief, QoL improvement, and subsequent total scores in CPSI were obtained with ESB than with EMS when treating refractory CPPS. We postulate that biofeedback in the ESB treatment, by guiding the identification of tight pelvic floor muscles and then training the patient to relax these muscles, may provide further help in relieving the uncomfortable conditions caused by CPPS. Animal and human studies have shown that adequate and sufficient muscle exercise diminishes the pain experience by its effect on the endogenous pain modulatory systems.34 The mechanism of the biofeedback-oriented muscle exercise was suggested to involve the promotion of b-endorphin release.35 Theoretically, ESB would
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be more suitable for patients with pelvic muscle tenderness or signs of neurologic system abnormality. We found that tenderness and tension of the pelvic floor musculature, including associated tissues, were commonly palpable during digital examination of our patients. Biofeedback in ESB may direct and educate patients with CPPS to strengthen their pelvic floor muscles.14 Improved pelvic muscle health, in turn, may result in less spasm and pain. In summary, ESB provokes increases in pelvic floor muscle redirection and decreases in bladder outlet resistance, which could be the key to why it outweighs EMS as a short-term CPPS treatment in our study.10 Some limitations to our study need to be mentioned. First, it is a retrospective, nonrandomized, single-center study on a limited group of patients, which probably created bias. Larger prospective controlled studies are still required to establish the overall generalization of the findings of this comparison study. Second, urinary symptoms were rated only by questionnaires. Additional urodynamic studies, perhaps including uroflowmetry, may increase the persuasiveness of the voiding improvement. Third, our follow-up period was only 12 weeks after completion of treatment, so longterm results may be valuable to validate our findings. Finally, the question remains of whether the treatment intensity of our biofeedback-directed exercise of the pelvic floor muscle could provoke b-endorphin release for pain relief. The answer remains elusive and requires further study. 5. Conclusion Both EMS and ESB physical therapy applied to the pelvic floor muscle are effective for pain reduction, increased QoL, and improvement of lower urinary tract symptoms in male CPPS patients who are refractory to medical treatments. The combination therapies of ES plus biofeedback demonstrate additional benefit in pain reduction and QoL when compared with EMS alone. Conflicts of interest The authors have no conflicts of interest to declare. References 1. Krieger JN, Nyberg Jr L, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282:236e7. 2. Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. Int J Antimicrob Agents 2008;31(Suppl 1):S85e90. 3. Nickel JC, Teichman JM, Gregoire M, Clark J, Downey J. Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial cystitis, and epididymitis in outpatient urological practice: the Canadian PIE Study. Urology 2005;66:935e40. 4. Nickel JC, Downey JA, Nickel KR, Clark JM. Prostatitis-like symptoms: one year later. BJU Int 2002;90:678e81. 5. Wenninger K, Heiman JR, Rothman I, Berghuis JP, Berger RE. Sickness impact of chronic nonbacterial prostatitis and its correlates. J Urol 1996;155:965e8. 6. Magistro G, Wagenlehner FM, Grabe M, Weidner W, Stief CG, Nickel JC. Contemporary management of chronic prostatitis/chronic pelvic pain syndrome. Eur Urol 2016;69:286e97. 7. Pontari MA, Ruggieri MR. Mechanisms in prostatitis/chronic pelvic pain syndrome. J Urol 2008;179(5 Suppl):S61e7. 8. Anothaisintawee T, Attia J, Nickel JC, Thammakraisorn S, Numthavaj P, McEvoy M, et al. Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis. JAMA 2011;305: 78e86. 9. Segura JW, Opitz JL, Greene LF. Prostatosis, prostatitis or pelvic floor tension myalgia? J Urol 1979;122:168e9. 10. Kaplan SA, Santarosa RP, D'Alisera PM, Fay BJ, Ikeguchi EF, Hendricks J, et al. Pseudodyssynergia (contraction of the external sphincter during voiding) misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a therapeutic option. J Urol 1997;157:2234e7. 11. Zermann DH, Ishigooka M, Doggweiler R, Schmidt RA. Neurourological insights into the etiology of genitourinary pain in men. J Urol 1999;161:903e8.
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Please cite this article in press as: Yang M-H, et al., Comparing electromagnetic stimulation with electrostimulation plus biofeedback in treating male refractory chronic pelvic pain syndrome, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.03.006