Int Urogynecol J (2001) 12:9–14 ß 2001 Springer-Verlag London Limited International Urogynecology Journal Original Article The Pain Cycle: Implications for the Diagnosis and Treatment of Pelvic Pain Syndromes K. Everaert, J. Devulder1, M. De Muynck1, S. Stockman1, H. Depaepe1, D. De Looze1, J. Van Buyten2 and W. Oosterlinck1 1 University Hospital of Ghent, Ghent; 2Sint Blasius Hospital, Sint Niklaas, Belgium Abstract: The aim of the study was to report our results of sacral nerve stimulation in patients with pelvic pain after failed conservative treatment. From 1992 to August 1998 we treated 111 patients (40 males, 71 females, ages 46 + 16 years) with chronic pelvic pain. All patients with causal treatment were excluded from this study. Pelvic floor training, transcutaneous electrical nerve stimulation (TENS) and intrarectal or intravaginal electrostimulation were applied and sacral nerve stimulation was used for therapy-resistant pain. The outcome of conservative treatment and sacral nerve stimulation (VAS <3/10; >50% pain relief) was related to symptoms of voiding dysfunction and dyschezia, and urodynamic proof of dysfunctional voiding, not to the pain localization or treatment modality. Outcome was inversely related to neuropathic pain. When conservative treatment failed, a test stimulation of the S3 root was effective in 16/26 patients, and 11 patients were implanted successfully with a follow-up of 36 + 8 months. So far no late failures have been seen. A longer test stimulation is needed in patients with pelvic pain because of a higher incidence of initial false positive tests. Our conclusion is that sacral nerve stimulation is effective in the treatment of therapy-resistant pelvic pain syndromes linked to pelvic floor dysfunction. Keywords: Neuromodulation; Neurostimulation; Pain; Pelvic floor; Urodynamics; Voiding dysfunction Correspondence and offprint requests to: Dr K. Everaert, Department of Urology, P6, De Pintelaan 185, B-9000 Ghent, Belgium. Introduction Pelvic pain is a diagnostic and therapeutic challenge for urologists, gynecologists, gastroenterologists and pain clinicians. It is often related to psychological and psychosomatic disorders [1] and many physicians are consulted because of the lack of adequate treatment. Pelvic pain syndromes such as spastic pelvic floor syndrome, urethral syndrome, prostatodynia, vaginismus, levator ani syndrome and fugative proctalgia are often related to psychological disorders and dysfunction [1] of the pelvic floor, with symptoms such as voiding dysfunction, urine retention, constipation, dyschezia and dyspareunia. Spasticity of the pelvic floor causes dysfunctions in the anterior, middle and/or posterior compartments of the pelvis, and is often accompanied by pelvic pain syndromes [1,2]. Although dysfunction of the pelvic floor seems to play an important role in the pathophysiology, we did not find any reports in the literature. Electrotherapy has been used in the treatment of pain since ancient times. Scribonus Largus (46 ad) treated headaches with electric eels (40–100 V, 100 Hz). In the 1960s the first reports appeared on transcutaneous electrical nerve stimulation (TENS) and dorsal column stimulation (DCS) as treatments for pain syndromes in all parts of the body [3]. The first reports on electrostimulation for bladder diseases appeared in the 1970s [4]. Only recently, in 1990, sacral nerve stimulation was introduced for the treatment of pelvic pain, voiding dysfunction and urge incontinence [5–9]. The aim of this study was to report our results of sacral nerve stimulation in patients with pelvic pain after failed conservative treatment and to improve patient selection and the success rate of future treatment. 10 Patients and Methods From January 1992 to August 1998 we treated 111 patients (40 men, 71 women, ages 46 + 16 years, range 17–80 years) with unexplained chronic pelvic pain. All were evaluated with a clinical examination, urine sediment and culture, urine cytology, urinary tract ultrasound or urography and a micturition chart. If relevant, a spermiogram and culture, cystoscopy, bladder biopsies, urodynamics, a neurophysiological evaluation of the painful dermatomes or a herniography were performed. All patients with curable diseases (infection, stone disease, cancer, obstruction, etc.) were excluded from the study. Interstitial cystitis was also excluded by bladder biopsy. A treatment and evaluation flowchart is depicted in Fig. 1. Patients with proven concomitant urodynamic dysfunctional voiding were treated with pelvic floor K. Everaert et al. training and/or analgesic electrostimulation (n = 61). If no dysfunctional voiding was present, analgesic electrostimulation was given alone (n = 50). Electrostimulation was given intrarectally (men), intravaginally (women) or as TENS, depending on the pain localization. Treatments were given 2–3 times a week and 10–20 sessions (10 sessions, twice weekly) were applied. The criteria for success were significant pain relief (VAS <3/10; >50% pain relief), assessed before and 2–4 weeks after the end of the treatment, on a visual analog scale grading the pain intensity. If these conservative treatments failed the patients were offered sacral nerve stimulation (n = 26). Pain localization, symptoms of voiding dysfunction, dyschezia and dyspareunia were obtained from the patient files (Table 1). From these it was possible to describe the type of pain as deep (n = 78), superficial (n = 33) or neuropathic (n = 13). Voiding dysfunction Fig. 1. Treatment and evaluation methods in 111 patients with chronic pelvic pain. VAS, visual analogue scale on pain intensity; PFT, pelvic floor training; ES, electrostimulation; IR, intrarectal; IV, intravaginal; SNS, sacral nerve stimulation. Treatment of Pelvic Pain Syndromes 11 Table 1. Symptoms and urodynamics of 111 patients with chronic pelvic pain. The treatment was determined by the urodynamic evidence of dysfunctional voiding and the pain localization (deep versus superficial pain) Normal micturition (n = 50) Deep pain Deep pelvis Urethra Prostate Superficial pain Penis Perineum Inguinal Scrotal Pudendal nerve Neuropathic pain Concomitant symptoms Voiding dysfunction Dyschezia Dyspareunia (n/n women) Urodynamics Sphincter instabilities, n Mean sphincter pressure, cmH2O* Compliance* Peaked flow pattern, n Normal flow pattern, n Qmax, ml/s* Dysfunctional voiding (n = 61) P value{ 14 6 4 13 22 18 NS 0.0414 0.0374 8 3 5 4 4 1 5 0 2 1 0.0303 NS NS NS NS 11 2 0.0178 7 3 4/17 58 26 39/54 0.0000 0.0017 NS 16 81+46 52+25 3 46 20+6 60 102+46 64+33 48 4 25+17 0.0017 0.022 NS 0.0000 0.0000 NS *.Mean + SD. .w2 test, Wilcoxon test. { was evaluated with uroflow and urodynamics. Dysfunctional micturition was characterized by a peaked uroflow pattern and confirmed with urodynamics (Gaeltec microtip catheters), Polygram software (Synectics– Medtronic). Patients with voiding dysfunction had an elevated mean resting closure pressure (>100 cmH2O) with sphincter instabilities (d >15 cmH2O) during filling cystometry and a non-obstructive micturition analysis with a hypo- or acontractile detrusor [2]. A summary of urodynamics for each subpopulation is presented in Table 1. TENS therapy (Staodyn TENS, model 4600, Staodynamics Inc., Longmount, USA) was given with external electrodes (two poles) on painful dermatomes. We applied 60–70 Hz to obtain long-lasting effects (gate control) and 2–10 Hz for immediate but short-term effects (endorphin release) [3,11,12]. Vaginal (women) or intrarectal (men) electrodes were used in ‘deep’ pain syndromes (pelvis, bladder, vagina, prostate), applying a low-frequency supramaximal current of 20 Hz (Urogyn 8900, Incare Medical Products, Paris, France). These low frequencies have been found empirically to be the most effective in the treatment of chronic deep pain [3]. Pelvic floor training was started without analgesic electrostimulation. Electrostimulation (30–50 Hz, 250 ms, twice 10 minutes intrarectal or intravaginal) was administered to patients without proprioceptive perception of the pelvic floor or with extremely weak voluntary contractility of the pelvic floor (Urogyn 8900, Incare Medical Products, Paris, France). The aim was to increase proprioceptive perception and to facilitate voluntary contractions. Once these therapeutic goals were obtained biofeedback training was given, focusing on pelvic floor relaxation. When these skills were achieved, pelvic relaxation was combined with uroflowmetry. If no pain relief was obtained after this treatment, 20 Hz [3] intravaginal or intrarectal electrostimulation or TENS was added to the therapy. If these conservative treatments were unsuccessful we suggested a percutaneous nerve evaluation test (PNE) [8]. This was performed in 26 patients (10 males, 16 females, ages 46 + 5 years) using a Medtronic screener (Medtronic Interstim, Lausanne, Switzerland) and a Flexon wire (Davis & Geck). Patients were stimulated unilaterally 24 hours a day, for as long as possible, for a maximum of 4 weeks. The stimulation parameters were 1–10 V, 14–21 Hz, and a pulse width of 210 ms [2]. If the patient responded well (>50% pain relief, VAS <3/10 and objective correction of the voiding dysfunction of relevant), we implanted a pulse generator and a Medtronic quadripolar electrode. The stimulation parameters were 0.8–3.6 V, 14–21 Hz, and a pulse width of 210 ms. The pulse frequency was only increased to 21 Hz when an amplitude of 3.6 V was insufficient for pain relief. The follow-up of the implanted patients was 32 months + 12 months (mean + SD). 12 K. Everaert et al. Statistical Analysis Comparison of groups was done with the w2 test. In the case of a 2 6 2 table a Yates’ correction for continuity was performed. Multinomial logit regression analysis was used to explain the probability that a certain observation will belong to a given category. The advantage over multivariable analysis tools is the fact that they permit control for multiple continuous variables and their interaction effects. They may also be used for predictions. Results Treatment results are presented in Table 2. Monovariate multinomial regression analysis (residual w2 87.5; P<0.0001; 111 cases included) revealed that pain relief was significantly better in patients with symptoms of voiding dysfunction and dyschezia than in those with dyspareunia. Relief was also better with decreasing age (P<0.0001) and better in men than in women (P<0.05). Urodynamic evidence of dysfunctional micturition was the main criterion of success (Wald score 83.3, P<0.0001). After correction for all the above-mentioned variables no significantly different treatment results were found between TENS, intravaginal–intrarectal electrostimulation or pelvic floor training (with or without electrostimulation). We treated 23 patients repetitively (1–3 episodes of 10–20 sessions a year). Among them, 17 were treated with intrarectal electrostimulation, 2 with intravaginal electrostimulation and 4 with TENS (combined with pelvic floor training in 16 cases). Another 2 female patients used TENS for 12 and 25 months. In 7 patients treated with pelvic floor training (combined with electrostimulation in 5 patients) no further treatment sessions were needed and 39 patients were lost to followup. A percutaneous nerve evaluation test was performed in 26 patients (Table 3). Among these, 16 failed with conservative treatment, 8 had partial but insufficient success with conservative treatment, and 2 used TENS on the sacral dermatomes for 1 year. Significant pain relief was obtained in 16 patients and was related to the presence of dysfunctional voiding. Of the 10 patients Table 2. Results of conservative treatment in 111 patients with chronic pelvic pain. Pain relief was related to concomitant symptoms and urodynamic evidence of pelvic floor dysfunction, not to the treatment modality chosen. Relief was inversely related to the presence of neuropathic pain n Deep pain Deep pelvis Urethra Prostate Superficial pain Penis Perineum Inguinal Scrotal Pudendal nerve VAS <3, <50% pain relief, n (%) 27 28 23 9 8 5 6 5 14 (52) 5 (18) 7 (30) 6 2 4 4 5 (67) (25) (80) (67) (100) VAS <3, 50–90% pain relief, n (%) 4 (15) 9 (320 4 (18) 0 3 0 1 0 (0) (37) (0) (17) (0) VAS <3, >90% pain relief, n (%) P value{ 9 (33) 14 (50)* 12 (52) NS NS NS 3 3 1 1 0 (33) (37) (20) (17) (0)* NS NS NS NS NS Neuropathic pain 13 12 (92) 1 (8) 0 (0)* 0.0004 Concomitant symptoms Voiding dysfunction Dyschezia Dyspareunia 65 28 43 7 (11) 3 (11) 14 (32) 20 (31) 9 (32) 11 (26) 38 (58)* 16 (57)* 18 (42) 0.0000 0.0409 NS Cystometry Sphincter instabilities, n Mean sphincter pressure, cmH2O Compliance 76 111 111 17 (22) 89+53 56+22 17 (23) 102+49 67+34 42 (55)* 98+34 60+17 NS NS NS Micturition analysis Normal micturition, n Dysfunctional voiding, n Qmax, ml/s 50 61 111 42 (84) 5 (8) 23+8 2 (4) 19 (31) 25+16 6 (12)* 37 (61)* 20+13 0.0000 0.0000 NS Therapy TENS Intrarectal–vaginal ES PF training (+ or 7 ES) 23 27 61 20 (87) 12 (44) 34 (56) 1 (4) 5 (19) 11 (18) 2 (9)* 10 (37) 16 (26) NS NS NS *.P<0.05, w2 test (>50% pain relief vs <50% pain relief). .Multinomial regression anlaysis (>50% pain relief vs <50% pain relief). VAS, visual analogue scale on pain intensity; TENS, transcutaneous electrical nerve stimulation; ES, electrostimulation; PF, pelvic floor. { Treatment of Pelvic Pain Syndromes 13 Table 3. Results of sacral nerve test stimulation in 26 patients with therapy-resistant chronic pelvic pain n VAS <3, <50% pain relief, n VAS <3, 50–90% pain relief, n VAS <3, >90% pain relief, n P value* Type of pain Deep pain Superficial pain Neuropathic pain 15 11 5 4 6 5 4 1 0 7 4 0 NS NS 0.0087 Concomitant symptoms Voiding dysfunction Dyschezia Dyspareunia 21 14 14 5 2 5 5 3 3 11 9 6 0.0087 0.0211 NS Urodynamics Dysfunctional voiding 19 3 5 11 0.0006 *.w2 test (>50% pain relief vs <50% pain relief). who did not respond to the test stimulation, 6 had pain relief for 24–48 hours and 1 for 4 days. A two-stage implant was performed in 3 patients and avoided the unnecessary insertion of a IPG pulse generator in 2 patients. Finally, we implanted a pulse generator and a unilateral quadripolar electrode (S3 root) in 11 patients. The stimulation parameters were 0.8–3.6 V, 14–21 Hz, and a pulse width of 210 ms. Three patients are awaiting insurance approval and 2 refused implantation when all the disadvantages and consequences of the surgery were explained. In September 1999, 9 our of 11 patients were satisfied with the treatment result. The two failures occurred immediately after insertion of the implant and are to be considered false positive PNE results (unless objective improvement of the uroflow pattern). One patient was explanted because of infection of the prosthesis, reducing the success rate to 8 out of 11. Revision following electrode migration was performed in 1 patient, in whom an earlier type of electrode, without fixed anchor, was used. So far no late failures have been seen. In 2 patients (on 3.6 V, both implanted in the first year) the frequency had to be increased to 21 Hz to avoid loss in battery lifetime. Discussion Sacral nerve stimulation is effective in the treatment of therapy-resistant pelvic pain syndromes linked to pelvic floor dysfunction, and has a long-lasting effect in the treatment of therapy-resistant chronic pelvic pain. The advantage of sacral nerve stimulation is that test stimulations are possible. However, in pelvic pain patients we found a high false positive PNE rate (n = 9) in the first days of the test. Longer test stimulation periods (>5 days of correct stimulation is needed) are particularly useful in patients with pelvic pain, and two- stage implants must be performed in doubtful cases [14]. Despite all our precautions, 2 out of 11 patients failed after implantation of the pulse generator. Patients with chronic pelvic pain are treated effectively with neuromodulation if concomitant pelvic floor muscle spasms are present. Pain cycle theory explains why pelvic floor spasms and pelvic pain are linked physiopathologically [3]. Sustained physical trauma (pelvic surgery, heat), physiological (inflammation), and psychological impulses cause increasing muscle tension and spasms, diminishing the blood supply to the muscle. The tonic muscle activity itself causes heat and the accumulation of metabolites (potassium ions, lactic acid, histamine, bradykinin, etc.). The resultant ischemia and accumulation of metabolites produces increasing pain. This mechanism is referred to as the pain cycle [3]. Muscle spasms of the pelvic floor may be either the cause or the result of sustained pain. As pelvic floor dysfunction is the main criterion of success, all patients with pelvic pain should be screened by uroflowmetry and abnormal flow patterns confirmed by urodynamics. In men [1] the Qmax is useful in the diagnosis of dysfunctional voiding, but not in women, as is seen from our results. Therefore, uroflow patterns are more diagnostic for dysfunctional voiding than in Qmax [15]. It is also important to screen chronic pelvic pain patients for dysfunctional voiding and not for the symptom of voiding dysfunction, as the latter can be secondary to pain drug treatment. TENS without pelvic floor training had the poorest results (20% success), which is rather low according to the literature [3]. However, the decision to give TENS depended on the pain localization, and patients with pain in the penis, groin, testicles or epididymis, who are less likely to have voiding dysfunction, were treated with TENS. Patients with prostatodynia or the urethral syndrome, who often suffer from dysfunctional voiding, were treated with intrarectal or intravaginal electrostimulation. So, the lower success rate for TENS in our series compared to the literature depends on patient selection, not on the therapy itself. 14 K. Everaert et al. Conclusion Sacral nerve stimulation is effective in the treatment of therapy-resistant pelvic pain syndromes linked to pelvic floor dysfunction. Sacral nerve stimulation had a longlasting effect in the treatment of chronic pelvic pain, but a longer test stimulation and, when in doubt, two-stage implants are suggested. 11. 12. 13. 14. References 1. Zermann DH, Doggweiler R, Ishigooka M, Schmidt RA. Male pelvic pain – a neuro-behavioral perspective. Neurourol Urodyn 1998;17:441 2. Everaert K, Plancke H, Lefevere F, Oosterlinck W. The urodynamic evaluation of neuromodulation in patients with voiding dysfunction. Br J Urol 1997;79:702–707 3. Mannheimer JF, Lampe GN. Clinical transcutaneous electrical nerve stimulation, 8th edn. F A Davis, 1988 4. Fall M, Carlsson CA, Erlandson BE. Electrical stimulation in interstitial cystitis. J Urol 1980;123:192–197 5. Lazorthes Y, Upton ARM, Mugica J, Ripart A. Neurostimulation, an overview. New York: Futura, 1985 6. Schmidt RA, Senn ES, Tanagho EA. Functional evaluation of sacral root integrity. Report of a technique. Urology 1990;35:388–392 7. Thon WF, Baskin LS, Jonas U, Tanagho EA, Schmidt RA. Neuromodulation of voiding dysfunction and pelvic pain. World J Urol 1991;9:138–141 8. Siegel SW. Managment of voiding dysfunction with an implantable neuroprosthesis. Urol Clin North Am 1992;19:163– 170 9. Koldewijn L, Rosier PF, Meuleman EJ, Koster AM, Debruyne FM, Van Kerrebroeck PE. Predictors of success with neuromodulation in lower urinary tract dysfunction: results of trial stimulation in 100 patients. J Urol 1994;152:2071–2075 10. Fowler CJ, Kirby RS, Harrison MSG. Deceleration bursts and complex repetitive discharges in the urethral sphincter associated with urinary rentention in young women. J Neurosurg Psychiatry 1985;48:1004–1009 Li CL, Bak A. Excitability characteristics of A- and C fibers in a peripheral nerve. Neurology 1976;50:67–79 Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971–978 Janknegt RA, Weil EHJ, Eerdmans PH. Improving neuromodulation technique for refractory voiding dysfunction: two-stage implant. Urology 1997;78:39–46 Everaert K, Van Laecke E, De Muynck M, Peeters H, Hoebeke P. Urodynamic assessment of voiding dysfunction and dysfunctional voiding in girls and women. Int Urogynecol J 2000;11:254–264 EDITORIAL COMMENT: This is a retrospective study challenging a difficult subject, i.e. the pelvic pain syndrome. The authors describe their clinical approach to this syndrome and present their results. Little is known about the pathophysiology of the pelvic pain syndrome. The group of patients described in this study is very heterogeneous, but the authors made an effort to identify those who might benefit from this approach and thus improve patient selection. The group of patients is not very well defined, i.e. unexplained chronic pelvic pain. Pelvic floor dysfunction was characterized by history of pelvic pain, micturition analysis and cystometry, excluding curable and identifiable diseases. This clinical approach of electrical stimulation and/or sacral nerve stimulation seems promising for patients who are often refractory to other treatments. However, more clinical research is necessary. This pilot study needs to be followed by a prospective trial in order to identify more precisely those who might be eligible for this kind of treatment.