Prostatic Diseases and Male Voiding Dysfunction Electroacupuncture Relieves Pain in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Three-arm Randomized Trial Sang-Hun Lee and Byung-Cheol Lee OBJECTIVES METHODS
To investigate the clinical effect of electroacupuncture (EA) for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We recruited 63 participants meeting the U.S. National Institutes of Health (NIH) consensus criteria for CP/CPPS. After the inclusion/exclusion criteria were applied, 39 men were randomized to 3 treatment groups: group 1, advice and exercise plus 12 sessions of EA; group 2, advice and exercise plus 12 sessions of sham EA (SEA); and group 3, advice and exercise alone (A&E) for 6 weeks. A total of 6 acupuncture points were used to stimulate the sacral nerve and release the piriformis muscle using an electrical pulse generator. Symptoms related to CP/CPPS were assessed using the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI). Prostaglandin E2 and ␤-endorphin levels in postmassage urine samples were measured using an enzyme-linked immunosorbent assay. At 6 weeks, the NIH-CPSI total score had decreased significantly in the EA group compared with the SEA and A&E groups (P ⬍ .001). On a subscale analysis of the NIH-CPSI, the EA group showed significant decreases in pain-related symptoms compared with the SEA and A&E groups (P ⬍ .01). All 12 EA participants experienced at least a 6-point decrease in the NIH-CPSI total score compared with 2 of 12 SEA participants (16.7%) and 3 of 12 A&E participants (25.0%; P ⬍ .0001). The mean prostaglandin E2 level in the postmassage urine samples had significantly decreased in the EA group (P ⫽ .023). In contrast, it had increased in the other 2 groups. In a 3-arm randomized trial investigating the clinical effects of EA on CP/CPPS, EA therapy proved to have independent therapeutic effects, particularly for pain relief superior to SEA or A&E therapy. UROLOGY 73: 1036 –1041, 2009. © 2009 Elsevier Inc.
hronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common, with a prevalence of 2%-10% among adult men worldwide.1 However, the current treatment strategies, including antibiotics, ␣-blockers, anti-inflammatory agents, and other medical agents, are not effective for all patients with CP/CPPS.2 In 2008, it was reported that acupuncture was almost twice as effective as sham acupuncture for CP/ CPPS in randomized, controlled clinical trials.3 Electroacupuncture (EA) therapy in a mouse model was demonstrated to be more effective in treating pain by producing
This study was supported by a Korea Science and Engineering Foundation grant funded by the Korean Government (MEST) (R11-2005-014). From the Division of Urology and Nephrology, Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea Reprint requests: Byung-Cheol Lee, O.M.D., Ph.D., Division of Urology and Nephrology, Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-Ku, Seoul 130-702 Republic of Korea. E-mail: email@example.com Submitted: August 13, 2008, accepted (with revisions): October 20, 2008
© 2009 Elsevier Inc. All Rights Reserved
a potent anti-inflammatory effect compared with needle insertion only.4 However, clinical trials to investigate the effect of EA for CP/CPPS have been insufficient.5 Through a 3-arm randomized study for CP/CPPS, we sought to determine the nonspecific effect independent of needle placement (EA vs advice and exercise alone [A&E]) and the specific effect of the needle’s intrinsic therapeutic action, such as the localization, stimulation, or needle depth (EA vs sham EA [SEA]). Pain and evidence of an inflammatory response are the common factors in CP/CPPS, and the role of prostaglandins in inflammation and pain perception has been widely recognized.6 Men with symptomatic CP/CPPS have been reported to have greater prostaglandin E2 and lower ␤-endorphin concentrations in their prostatic fluid than those of asymptomatic controls.6,7 Moreover, EA therapy has been demonstrated to possess anti-inflammatory properties by lowering proinflammatory molecules, including prostaglandin E2.8,9 Therefore, we investigated 0090-4295/09/$34.00 doi:10.1016/j.urology.2008.10.047
how EA therapy is associated with the prostaglandin E2 and ␤-endorphin levels in postmassage urine samples from participants with CP/CPPS.
MATERIAL AND METHODS Study Population Overall, we recruited 63 men who met the clinical diagnosis of CP/CPPS (category III) according to the National Institutes of Health (NIH) consensus criteria from the Oriental Medical Hospital, Kyung Hee University Medical Center from June 2007 to December 2007. These patients had a history of CP/ CPPS refractory to standard conventional therapy, including antibiotics, ␣-blockers, and anti-inflammatory agents. The eligibility requirements were age ⬎18 years, NIH Chronic Prostatitis Symptom Index (NIH-CPSI) total score ⬎15 (scale 0-43), and symptoms for ⬎3 months during the previous 6 months.10 After taking the medical history and physical examination, participants were excluded from the study if they had a urologic disease (eg, acute prostatitis or bacterial prostatitis, benign prostatic hyperplasia, prostate cancer, urinary tuberculosis, urinary tract infection, bladder stone, urethral stricture, interstitial cystitis, urethritis, neuropathic bladder, bladder cancer, hematuria), medication history (eg, antibiotics, muscle relaxants, nonsteroidal anti-inflammatory drugs, or analgesics within 1 month or presumed to have), diseases that influence urologic symptoms (eg, brain disease, sexually transmitted disease), or any acute disease or disease requiring treatment. Patients ⬎50 years old were excluded from the study to minimize the confounding role of benign prostatic hyperplasia-related symptoms. We also excluded patients with a history of acupuncture within the previous 6 months. The institutional review board of the Oriental Medical Hospital approved this project, and it was conducted in accordance with the Declaration of Helsinki. All participants signed a consent form after reading the protocol.
Study Design After enrollment, the 39 men were randomized 1:1:1 to 1 of the following groups: A&E plus EA, A&E plus SEA, or A&E alone, using a computer-generated, random block design. One patient from each group withdrew consent before the first intervention. The remaining 36 participants received the advice and exercise package, which consisted of hot sitz baths and 30 minutes of fast-paced walking on indoor-outdoor track. The EA therapy protocol included a total of 6 acupuncture points at the bilateral BL32 (zhongliao), BL33 (ciliao), and GB30 (huantiao) were selected according to the theory of neuroanatomy and myofascial pain syndromes. In brief, both BL32 and BL33, located in the second and third posterior sacral foramen on the sacrum, were selected to stimulate the sacral nerve.11 GB30, located at the junction of the lateral one third and medial two thirds of the distance between the great trochanter and the hiatus of the sacrum, was chosen for releasing the myofascial trigger point of the piriformis muscle.12 All acupuncture points were prepared with 70% alcohol pads, and disposable stainless steel needles (40 ⫻ 0.25 mm, Dongbang Acupuncture, Chungnam, Republic of Korea) were used. With participants lying prone, the needles were placed perpendicularly about 30 mm deep and stimulated electrically at both UROLOGY 73 (5), 2009
right and left acupuncture points with a frequency of 4 Hz and an intensity of 5-10 mA (tolerable strength) with continuous stimulation by the pulse generator (PG-306, Suzuki Iryoki, Japan).13 At GB30, disposable stainless steel needles (70 ⫻ 0.30 mm, Dongbang Acupuncture) were inserted deeply to reach the myofascial trigger point of the piriformis muscle. The SEA therapy protocol included the same number and type of needle, duration, and frequency of sessions as for the EA treatment, but the treatment was delivered superficially at nonacupuncture points 15 mm to the lateral of each corresponding acupuncture point. The points were not stimulated electrically, but the sound of the pulse generator was heard by the participants. The participants in the EA and SEA groups were given treatment twice a week for 20 minutes for 6 weeks by a practitioner who had had 6 years of acupuncture training and 3 more years of clinical experience. Those receiving EA or SEA therapy were treated on alternate days to prevent crosstalk among groups, which could have compromised the blinded study design.
Evaluations and Specimen Collection The primary outcome was the change in the NIH-CPSI total score from baseline to endpoint (6 weeks). The NIH-CPSI was administered at the baseline visit and the 3-week visit. Secondary outcomes included changes in the pain, voiding, and quality-of-life subscales of the NIH-CPSI, as well as International Prostate Symptom Score. As defined by previous reports, NIHCPSI responders were defined as men who experienced a decrease of ⱖ6 points in the total NIH-CPSI score compared with the baseline score, a ⱖ25% decrease in the total NIH-CPSI score compared with baseline (perceptible improvement), or a ⱖ50% decrease in the total NIH-CPSI score compared with baseline (significant improvement).14 As secondary outcomes, the postmassage urine samples, including prostatic fluid, were obtained at baseline and endpoint by digital rectal examination for prostaglandin E2 and ␤-endorphin. The urine samples were preserved at ⫺80°C until the measurement of prostaglandin E2 and ␤-endorphin. They were analyzed using enzyme-linked immunosorbent assay kits (prostaglandin E2, Caymen Chemical, Ann Arbor, MI; ␤-endorphin, Peninsula Laboratories, San Carlos, CA) according to the manufacturer’s instructions.
Statistical Analysis The study was designed to have a statistical power of 90% to detect a difference between the EA group and the SEA group of 5.0 and between the EA group and the A&E group of 7.0 in the NIH-CPSI score, on the basis of a published standard deviation of 4.8 in the NIH-CPSI score and a 2-sided ␣ value of 0.05.5 These calculations and values required the enrollment of 33 men, and the number was increased to a target enrollment of 39 to account for a potential dropout rate of ⱕ20%. All analyses were conducted according to the intention-totreat principle; thus, all data obtained from men who did not complete the study were included in the final analyses. The data are presented as the mean ⫾ standard deviation, except for prostaglandin E2 and ␤-endorphin, which are expressed as the mean ⫾ standard error. The baseline demographics and clinical variables were compared among the treatment groups using the 1037
Table 1. Demographics and clinical characteristics* Variable
EA (n ⫽ 12)
SEA (n ⫽ 12)
Age (y) Body mass index (kg/m2) Marital status† Single Married or living with partner Employment status† Employed Unemployed Symptom duration (y) NIH-CPSI Total score (range 0-43) Pain subscore (range 0-21) Urinary subscore (range 0-10) QOL subscore (range 0-12) IPSS score (range 0-35)
39.8 ⫾ 5.8 22.9 ⫾ 2.5
36.4 ⫾ 5.8 23.4 ⫾ 2.2
A&E (n ⫽ 12) 38.2 ⫾ 6.9 22.8 ⫾ 2.8
3 (25.0) 9 (75.0)
5 (41.7) 7 (58.3)
4.0 (33.3) 8.0 (66.7)
10 (83.3) 2 (16.7) 6.8 ⫾ 6.0
9 (75.0) 3 (25.0) 7.0 ⫾ 4.9
9.0 (75.0) 3.0 (25.0) 5.6 ⫾ 5.5
26.9 ⫾ 5.2 12.2 ⫾ 2.5 5.3 ⫾ 3.0 9.4 ⫾ 1.8 18.8 ⫾ 10.0
25.5 ⫾ 3.6 11.8 ⫾ 2.7 3.8 ⫾ 2.8 9.8 ⫾ 1.6 11.2 ⫾ 10.1
28.0 ⫾ 6.7 13.5 ⫾ 3.8 5.3 ⫾ 2.2 9.3 ⫾ 2.1 16.8 ⫾ 7.1
EA ⫽ electroacupuncture; SEA ⫽ sham electroacupuncture; A&E ⫽ advice and exercise alone; NIH-CPSI ⫽ National Institutes of Health Chronic Prostatitis Symptom Index; QOL ⫽ quality of life; IPSS ⫽ International Prostate Symptom Score. Data presented as mean ⫾ standard deviation or number of patients, with percentages in parentheses. * P value determined using Kruskall-Wallis test, except as noted otherwise; all P values nonsignificant. † P value determined using 2 test.
Kruskall-Wallis test or 2 test. The reduction in scores of the NIH-CPSI (total CPSI, pain subscale, urinary subscale, and quality-of-life subscale) and International Prostate Symptom Score at 3 and 6 weeks from the baseline were compared among the treatment groups using the Kruskall-Wallis test, followed by Dunn’s post hoc test. The differences between the responders of the 3 groups were analyzed using the 2 test or Fisher’s exact test. Prostaglandin E2 and ␤-endorphin were compared before and after treatment using the Wilcoxon matched pairs test. All P values are 2-tailed, and significance was set at P ⬍ .05. All statistical analyses were performed using the GraphPad Prism for Windows, version 5.01 (GraphPad Software, San Diego, CA).
RESULTS Of 36 men, 32 completed the study. Four men withdrew because of their inability to comply with the study requirements (EA group ⫽ 1, SEA group ⫽ 2, and A&E group ⫽ 1). The subjects had a mean age of 38.1 years (range 24-49), a mean duration of 6.5-years since the diagnosis of CP/CPPS, and a mean NIH-CPSI total score of 26.8 points (range 20-41). No significant difference was found among the groups in baseline demographic and clinical characteristics (Table 1). Adverse events occurred in only 1 SEA participant; the patient experienced lower back pain near the needling site that resolved quickly. Decreases in the NIH-CPSI scores from baseline were observed in all groups at 3 and 6 weeks. At 3 weeks, no significant differences were seen in the NIH-CPSI total scores among the treatment groups. However, in the pain symptom component of the NIH-CPSI at 3 weeks, the EA group showed a significant reduction (⫺3.7 ⫾ 2.6) compared with the SEA group (⫺1.4 ⫾ 2.0, P ⬍ .05). Of the 12 men in the EA group, 8 (66.7%) experienced at least a 6-point decrease in NIH-CPSI total score compared with 2 of the 12 SEA participants (16.7%) and 2 of 1038
the 12 A&E participants (16.7%; P ⫽ .011). A total of 7 participants (58.3%) in the EA group, 2 (16.7%) in SEA group, and 1 (8.3%) in A&E group were 25% responders (P ⫽ .014). At 6 weeks, the EA group showed a significant reduction (⫺9.5 ⫾ 3.7) in the NIH-CPSI total score compared with the SEA group (⫺3.5 ⫾ 3.6, P ⬍ .001) and A&E group (⫺3.5 ⫾ 2.4, P ⬍ .001). In the pain symptom component of the NIH-CPSI at 6 weeks, the EA group showed a significant reduction (⫺5.2 ⫾ 1.9) compared with the SEA group ⫺1.6 ⫾ 1.8, P ⬍ .001) and the A&E group (⫺2.2 ⫾ 1.8, P ⬍ .01). For the other components of the NIH-CPSI, including the urinary symptom and quality-of-life scores, the EA group showed no significant reduction compared with the other treatment groups. All 12 EA participants experienced at least a 6-point decrease in the NIH-CPSI total score compared with 2 of the 12 SEA men (16.7%) and 3 of the 12 A&E men (25.0%) (P ⬍ .0001). A total of 9 participants (75.0%) in the EA group, 2 (16.7%) in the SEA group, 2 (16.7%) in the A&E group were 25% responders (P ⫽ .003). Three participants in the EA group (25.0%) were 50% responders (P ⫽ .038). In the International Prostate Symptom Score, no significant differences were found among the treatment groups during the 6 weeks (Table 2). In the postmassage urine analysis, prostaglandin E2 decreased significantly from 98.18 ⫾ 19.36 pg/mL to 71.43 ⫾ 14.98 pg/mL in the EA group during the 6-week period (P ⫽ .023). In contrast, it had increased in the other groups with no statistical significance (Fig. 1A). The ␤-endorphin level did not change significantly in any group during the 6-week period (Fig. 1B).
COMMENT Because the etiologic factors of CP/CPPS remain unknown, various treatment therapies have been used, inUROLOGY 73 (5), 2009
Table 2. Net changes in symptom score from baseline and in responders at 3 and 6 weeks
Variable 3 wk NIH-CPSI Total score Pain subscore Urinary subscore QOL subscore Responder† ⱖ6 point decrease ⱖ25% improvement ⱖ50% improvement IPSS 6 wk NIH-CPSI Total score Pain subscore Urinary subscore QOL subscore Responder‡ ⱖ6 point decrease ⱖ25% improvement ⱖ50% improvement IPSS
Net Change From Baseline EA (n ⫽ 12) SEA (n ⫽ 12) A&E (n ⫽ 12)
EA vs SEA
P Value* EA vs A&E
SEA vs A&E
NS NS NS NS
NS NS NS NS
⫺7.0 ⫾ 5.1 ⫺3.7 ⫾ 2.6 ⫺1.2 ⫾ 1.4 ⫺2.2 ⫾ 2.0
⫺3.2 ⫾ 3.5 ⫺1.4 ⫾ 2.0 ⫺0.7 ⫾ 1.2 ⫺1.1 ⫾ 1.6
⫺3.1 ⫾ 2.5 ⫺2.1 ⫾ 1.1 ⫺0.3 ⫾ 1.0 ⫺0.7 ⫾ 1.4
8 (66.7) 7 (58.3) 0 (0.0) ⫺4.2 ⫾ 3.4
2 (16.7) 2 (16.7) 0 (0.0) ⫺2.0 ⫾ 3.1
2 (16.7) 1 (8.3) 0 (0.0) ⫺1.7 ⫾ 1.8
.036 NS NS NS
.036 .027 NS NS
NS NS NS NS
⫺9.5 ⫾ 3.7 ⫺5.2 ⫾ 1.9 ⫺1.8 ⫾ 1.5 ⫺2.6 ⫾ 2.4
⫺3.5 ⫾ 3.6 ⫺1.6 ⫾ 1.8 ⫺0.7 ⫾ 1.4 ⫺1.3 ⫾ 1.8
⫺3.5 ⫾ 2.4 ⫺2.2 ⫾ 1.8 ⫺0.4 ⫾ 1.5 ⫺0.9 ⫾ 1.1
⬍.001 ⬍.001 NS NS
⬍.001 ⬍.01 NS NS
NS NS NS NS
12 (100.0) 9 (75.0) 3 (25.0) ⫺5.7 ⫾ 4.5
2 (16.7) 2 (16.7) 0 (0.0) ⫺2.4 ⫾ 3.6
3 (0.25) 2 (16.7) 0 (0.0) ⫺3.0 ⫾ 3.7
⬍.001 .012 NS NS
⬍.001 .012 NS NS
NS NS NS NS
NS ⬍.05 NS NS
NS ⫽ not significant; other abbreviations as in Table 1. Responders classified into 3 groups: decrease of ⱖ6 points, ⱖ25% improvement, and ⱖ50% improvement in total NIH-CPSI score compared with baseline. * P value determined using Kruskall-Wallis test followed by Dunn’s post hoc test or Fisher’s exact test between 2 groups (2 ⫻ 2 table). † P values among 3 groups determined by 2 test (2 ⫻ 3 table): .011 for ⱖ6-point decrease and .014 for ⱖ25% improvement at 3 weeks. ‡ P values among 3 groups determined by 2 test (2 ⫻ 3 table): ⬍ .0001 for ⱖ6-point decrease, .003 for ⱖ25% improvement, and .038 for ⱖ50% improvement at 6 weeks.
cluding antibiotics, anti-inflammatory agents, ␣-blockers, phytotherapy, biofeedback, hyperthermia, electrical stimulation, and acupuncture.2 Recent studies have suggested that acupuncture therapy could benefit men with CP/CPPS, owing to the hypothesis of multimodal treatment effects, which could include pain relief by way of potential anti-inflammatory and neuromodulatory mechanisms.5 To the best of our knowledge, this study was the first 3-arm randomized clinical trial of EA for CP/CPPS. Our results have demonstrated that EA therapy could be significantly beneficial after 6 weeks compared with both SEA and A&E. When the net change of the NIH-CPSI scores was compared at 6 weeks, the EA group showed a significant reduction compared with the other treatment groups (P ⬍ .001). All 12 EA participants experienced at least a 6-point decrease in the total NIH-CPSI score, and the responders’ percentage showing a ⱖ25% decrease in total NIH-CPSI score included approximately 75.0% of the EA group in contrast to 16.7% of the SEA group and 16.7% of the A&E group (P ⫽ .003). Additional subscale analysis of the NIH-CPSI showed that EA therapy had more of an affect on the pain symptom scores only when compared with the SEA and A&E groups. This suggests that EA therapy might be superior in relieving pain compared with other treatments, which is related to the selected acupuncture points and electric stimulation. UROLOGY 73 (5), 2009
In this study, we used only 6 acupuncture points because of the theory of neuroanatomy and myofascial pain syndrome. In brief, the needles to BL32 and BL33, which are located in the second and third posterior sacral foramen, could stimulate the segment of the sacral nerve.11 These segmental approaches would generally be found to produce a more intense analgesic response because of direct inhibition at the spinal cord level.15 In particular, transforamenal sacral nerve stimulations could have beneficial effects on the severity and frequency of chronic intractable pelvic pain.16 In addition, the electrical stimulation by the pulse generator would be more beneficial for relieving pain, in particular chronic pain.17 The needles to the other EA point GB30, located on the myofascial trigger point of piriformis muscle, could relax the external pelvic floor muscles and relieve pelvic tenderness. Frequently, the piriformis trigger points significantly contribute to complex myofascial pain syndromes in the pelvic and hip regions.12 Pelvic tenderness was reported to be present in one half of the patients with CP/CPPS compared with 7% of asymptomatic controls; those with tenderness had a statistically significantly greater NIHCPSI total score and pain subscore than those who did not report tenderness.18 In the present study, EA showed its effectiveness in the NIH-CPSI total score and pain subscore, possibly resulting from EA therapy to GB30 influencing the pelvic tenderness and to BL32 and BL33 stimulating the sacral nerve. 1039
postmassage urine analysis in this study, the mean prostaglandin E2 levels in the EA group decreased significantly but increased in both the SEA and the A&E groups. The limitations of our study were the small number of patients (n ⫽ 36) and the short study period, only 6 weeks. Therefore, a larger study with longer follow-up is necessary to confirm the benefits of EA therapy on prostate cases with CP/CPPS.
CONCLUSIONS From this 3-arm study of CP/CPPS investigating the clinical effect of EA on the prostate, EA therapy seems to have independent therapeutic effects, in particular a pain relief effect superior to SEA or A&E therapy, and its clinical effect might be associated with the decrease in the prostaglandin E2 levels in postmassage urine samples. References
Figure 1. (A) Mean prostaglandin E2 (PGE2) levels and (B) mean ␤-endorphin (END) levels in postmassage urine in each group before and after treatment. *P ⬍ .05. EA, electroacupuncture; Sham EA, sham electroacupuncture; AE, advice and exercise alone.
Our clinical study was also designed to investigate whether EA therapy for CP/CPPS influences the levels of prostaglandin E2 and ␤-endorphin as secondary outcomes. Prostaglandin E2 produced in the local inflammatory site is essential in initiating and maintaining inflammatory hyperalgesia.7,9 A clinical study showed that men with symptomatic CP/CPPS have greater prostaglandin E2 concentrations in prostatic fluid than asymptomatic controls.6,7 It suggested that the pain in CP/CPPS could be a result of increased prostaglandin production, which could then inhibit local production of ␤-endorphin. Therefore, any therapy lowering prostaglandin E2 levels within the prostate would be beneficial to men with CP/CPPS. EA therapy has been reported to have antiinflammatory properties by regulating proinflammatory cytokines and cyclooxygenase 2 expression in both peripheral and central nociceptive sites.8,9 We collected postmassage urine samples instead of expressed prostatic secretions, based on the idea that after prostatic massage, prostatic secretions exit into the posterior urethra and, therefore, can be found in the urine after micturition.19 According to 1040
1. Krieger JN, Riley DE, Cheah PY, et al. Epidemiology of prostatitis: new evidence for a world-wide problem. World J Urol. 2003;21: 70-74. 2. Capodice JL, Bemis DL, Buttyan R, et al. Complementary and alternative medicine for chronic prostatitis/chronic pelvic pain syndrome. Evid Based Complement Alternat Med. 2005;2:495-501. 3. Lee SW, Liong ML, Yuen KH, et al. Acupuncture versus sham acupuncture for chronic prostatitis/chronic pelvic pain. Am J Med. 2008;121:79-85. 4. Kim HW, Roh DH, Yoon SY, et al. The anti-inflammatory effects of low- and high-frequency electroacupuncture are mediated by peripheral opioids in a mouse air pouch inflammation model. J Altern Complement Med. 2006;12:39-44. 5. Chen R, Nickel JC. Acupuncture ameliorates symptoms in men with chronic prostatitis/chronic pelvic pain syndrome. Urology. 2003;61:1156-1159. 6. Shahed AR, Shoskes DA. Correlation of beta-endorphin and prostaglandin E2 levels in prostatic fluid of patients with chronic prostatitis with diagnosis and treatment response. J Urol. 2001;166: 1738-1741. 7. Bauer HW, Bach D. Prostaglandin E2 in prostatitis and prostatic adenoma. Urol Int. 1986;41:139-144. 8. Moon PD, Jeong HJ, Kim SJ, et al. Use of electroacupuncture at ST36 to inhibit anaphylactic and inflammatory reaction in mice. Neuroimmunomodulation. 2007;14:24-31. 9. Lee JH, Jang KJ, Lee YT, et al. Electroacupuncture inhibits inflammatory edema and hyperalgesia through regulation of cyclooxygenase synthesis in both peripheral and central nociceptive sites. Am J Chin Med. 2006;34:981-988. 10. Propert KJ, Alexander RB, Nickel JC, et al. Design of a multicenter randomized clinical trial for chronic prostatitis/chronic pelvic pain syndrome. Urology. 2002;59:870-876. 11. Bergström K, Carlsson CP, Lindholm C, et al. Improvement of urge- and mixed-type incontinence after acupuncture treatment among elderly women—a pilot study. J Auton Nerv Syst. 2000;79: 173-180. 12. Cummings M. Piriformis syndrome. Acupunct Med. 2000;18:108121. 13. Barlas P, Ting SL, Chesterton LS, et al. Effects of intensity of electroacupuncture upon experimental pain in healthy human volunteers: a randomized, double-blind, placebo-controlled study. Pain. 2006;122:81-89. 14. Nickel JC, Narayan P, McKay J, et al. Treatment of chronic prostatitis/chronic pelvic pain syndrome with tamsulosin: a randomized double blind trial. J Urol. 2004;171:1594-1597.
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18. Shoskes DA, Berger R, Elmi A, et al., for the Chronic Prostatitis Collaborative Research Network Study Group. Muscle tenderness in men with chronic prostatitis/chronic pelvic pain syndrome: the chronic prostatitis cohort study. J Urol. 2008;179: 556-560. 19. Ludwig M, Schroeder-Printzen I, L端decke G, et al. Comparison of expressed prostatic secretions with urine after prostatic massage: a means to diagnose chronic prostatitis/inflammatory chronic pelvic pain syndrome. Urology. 2000;55:175-177.