The history of sacral neuromodulation in Canada.

Sacral neuromodulation (SNM) has been used for the past 30 years, with significant improvements in the implantation technique and technology over the last several years. Canadian centers were involved with this technique from the very beginning by participating in several multicenter clinical trials and engaging in basic and clinical research. Presently, six Canadian centers continue to have SNM implantation programs.

International Continence Society best practice statement for use of sacral neuromodulation.

AIMS: Sacral neuromodulation (SNM) is an accepted therapy for a variety of conditions. However, despite over 20 years of experience, it remains a specialized procedure with a number of subtleties. Here we present the recommendations issued from the International Continence Society (ICS) SNM Consensus Panel. METHODS: Under the auspices of the ICS, eight urologists, three colorectal surgeons and two urogynecologists, covering a wide breadth of geographic and specialty interest representation, met in January 2017 to discuss best practices for neuromodulation. Suggestions for statements were submitted in advance and specific topics were assigned to committee members, who prepared and presented supporting data to the group, at which time each topic was discussed in depth. Best practice statements were formulated based on available data. This document was then circulated to multiple external reviewers after which final edits were made and approved by the group. RESULTS: The present recommendations, based on the most relevant data available in the literature, as well as expert opinion, address a variety of specific and at times problematic issues associated with SNM. These include the use of SNM for a variety of underlying conditions, need for pre-procedural testing, use of staged versus single-stage procedures, screening for success during the trial phase, ideal anesthesia, device implantation, post-procedural management, trouble-shooting loss of device function, and future directions for research. CONCLUSIONS: These guidelines undoubtedly constitute a reference document, which will help urologists, gynecologists, and colorectal surgeons optimize their use of SNM for refractory urinary urgency and frequency, UUI, NOR, and FI.

Does Psychological Disturbance Predict Explantation in Successful Pelvic Neuromodulation Treatment for Bladder Dysfunction? A Short Series.

INTRODUCTION: Sacral neuromodulation (SNM) is a safe and effective therapy for patients with lower urinary tract dysfunction (LUTD). It is used in patients who have exhausted conservative and first line therapeutic options. The selection of eligible candidates could predict a successful therapeutic outcome. Although many factors have been identified, psychological/psychiatric disturbances are neither well understood nor are routinely evaluated prior to implantation. CASE REPORTS: We report three cases where identified psychological/psychiatric disturbances post-implantation could have influenced explantation in an otherwise successful implantation of SNM device assessed both subjectively and objectively. The device had to be explanted in two of the three. One more patient has requested but has not-yet undergone explantation and is receiving treatment for severe depression. One of the explanted cases has successfully undergone re-implantation after successful treatment of her diagnosed psychological condition, while the other's request for re-implantation has not yet been fulfilled. CONCLUSIONS: Psychological/psychiatric disturbance have possibly affected the treatment outcome and explantation of SNM in our patients despite a high success in resolution of the urinary symptoms. Addressing such disturbances when determining patient eligibility for SNM therapy could reduce the explantation rate after a successful therapeutic response, and is an interesting point of interest for future research into predictors of successful SNM implantation and therapy.

A Phase-Based Electrical Plethysmography Approach to Bladder Volume Measurement.

Neuromodulation approaches to treating lower urinary tract dysfunction could be substantially improved by a sensor able to detect when the bladder is full. A number of approaches to this problem have been proposed, but none has been found entirely satisfactory. Electrical plethysmography approaches attempt to relate the electrical impedance of the bladder to its volume, but have previously focused only on the amplitudes of the measured signals. We investigated whether the phase relationships between sinusoidal currents applied through a pair of stimulating electrodes and measured through a pair of recording electrodes could provide information about bladder volume. Acute experiments in a rabbit model were used to investigate how phase-to-volume or amplitude-to-volume regression models could be used to predict bladder volumes in future recordings, with and without changes to the saline conductivity. Volume prediction errors were found to be 6.63 ± 1.12 mL using the phase information and 8.32 ± 3.88 mL using the amplitude information (p = 0.44 when comparing the phase and amplitude results, n = 6), where the volume of the filled bladder was about 25 mL. When a full/empty binary decision rule was applied based on the regression model, the difference between the actual threshold that would result from this rule and the desired threshold was found to be 4.24 ± 0.65 mL using the phase information and 106.92 ± 189.82 mL using the amplitude information (p = 0.03, n = 6). Our results suggest that phase information can form the basis for more effective and robust electrical plethysmography approaches to bladder volume measurement.

Economic evaluation of sacral neuromodulation in overactive bladder: A Canadian perspective.

INTRODUCTION: Refractory overactive bladder (OAB) with urge incontinence is an underdiagnosed condition with substantial burden on the healthcare system and diminished patient's quality-of-life. Many patients will fail conservative treatment with optimized medical-therapy (OMT) and may benefit from minimally invasive procedures, including sacral-neuromodulation (SNM) or botulinum-toxin (BonT-A). The goal of this study was to estimate the cost-efectiveness of SNM vs. OMT and BonT-A as important parameters from coverage and access to a therapy. METHODS: A Markov model with Monte-Carlo simulation was used to assess the incremental cost effectiveness ratio (ICER) of SNM vs. BonT-A and OMT both in deterministic and probabilistic analysis from a provincial payer perspective over a 10-year time horizon with 9-month Markov-cycles. Clinical data, healthcare resource utilization, and utility scores were acquired from recent publications and an expert panel of 7 surgeons. Cost data (2014-Dollars) were derived from provincial health insurance policy, drug benefit formulary, and hospital data. All cost and outcomes were discounted at a 3% rate. RESULTS: The annual (year 1-10) incremental quality-adjusted life years for SNM vs. BonT-A was 0.05 to 0.51 and SNM vs. OMT was 0.19 to 1.76. The annual incremental cost of SNM vs. BonT-A was $7237 in year 1 and -$9402 in year 10 and was between $8878 and -$11 447 vs. OMT. In the base-case deterministic analysis, the ICER for SNM vs. BonT-A and OMT were within the acceptable range ($44 837 and $15 130, respectively) at the second year of therapy, and SNM was dominant in consequent years. In the base-case analysis the probability of ICER being below the acceptability curve (willingness-to-pay $50 000) was >99% for SNM vs. BonT-A at year 3 and >95% for OMT at year 2. CONCLUSION: SNM is a cost-effective treatment option to manage patients with refractory OAB when compared to either BonT-A or OMT. From a Canadian payers' perspective, SNM may be considered a first-line treatment option in management of patients with OAB with superior long-term outcomes. Similar to all economic analysis, this study has limitations which are based on the assumptions of the used model.

Mechanism of action of sacral nerve stimulation using a transdermal amplitude-modulated signal in a spinal cord injury rodent model.

INTRODUCTION: : Sacral neuromodulation (SNM) is an effective treatment modality for several urological problems, including neurogenic bladder. However, the invasiveness of this technique makes it unsuitable for many patients. We present a novel transdermal amplitude-modulated signal (TAMS) that may provide a non-invasive alternative to implantable SNM to treat neurogenic detrusor overactivity (NDO). METHODS: : In this study, we investigated the mechanism of action of non-invasive SNM using TAMS on our established spinal cord injury (SCI) animal model. We demonstrated that spinally transected rats develop urinary bladder hyper-reflexia after 3 weeks of SCI, indicated by the presence of uninhibited contractions, increased resting pressure, increased threshold pressure and increased maximum voiding pressure. RESULTS: : Short-term neurostimulation affected urodynamics parameters by significantly reducing the threshold pressure (p = 0.02). Spinal transection also increased calcitonin gene-related protein (CGRP) concentration in the L6 dorsal root ganglia; whereas, neurostimulation significantly reduced CGRP concentration in L6 (p = 0.03). CONCLUSION: : TAMS caused a reduction in NDO by inhibiting C-fibre activity.

Single-session primary high-intensity focused ultrasonography treatment for localized prostate cancer: biochemical outcomes using third generation-based technology.

UNLABELLED: What's known on the subject? and What does the study add? The experience with HIFU as a minimally invasive treatment for localized prostate cancer is relatively new and most reports are from European centres. Our study is unique in five regards: 1. Data was collected prospectively. 2. All patients were treated with contemporary technology. 3. Outcomes are reported after a single HIFU session using two definitions of biochemical failure that have the ability to predict longer-term clinical failure after primary ablative therapies for prostate cancer (Stuttgart definition for HIFU and Horwitz definition for radiation). 4. All patients were treated in a single centre. 5. No patients underwent peri-HIFU TURP. The present study represents the largest North American prospective cohort of primary HIFU for prostate cancer with mid-term oncological outcome data. OBJECTIVE: To assess 4-year biochemical failure (BCF) rates in patients after high-intensity focused ultrasonography (HIFU) treatment using the Horwitz and Stuttgart definitions. PATIENTS AND METHODS: A total of 447 consecutive patients were treated with a single session of HIFU between May 2005 and December 2010. Follow-up included prostate-specific antigen (PSA) measurement every 3 months during the first year and every 6 months thereafter. Patients who had previously received radiation, androgen deprivation or HIFU therapy, and patients with <2 consecutive PSA measurements were excluded. BCF was reported using the Stuttgart (PSA nadir + 1.2 ng/mL rising) and the Horwitz (two consecutive increases of at least 0.5 ng/mL) definitions. RESULTS: In all, 402 patients met the inclusion criteria and the median (range) follow-up was 24 (6-48) months. Of these patients, 183 (45.5%) had low and 219 (54.5%) had intermediate D'Amico's risk stratification disease. Mean and median absolute PSA nadir levels were 0.36 ± 0.69 and 0.1 ng/mL (Q(1):0, Q(3):0.37), respectively and these were achieved in median time of 3 months. Overall 4-year mean (range) BCF-free rates were 68 (61-75)% and 72 (68-77)% according to the Stuttgart and Horwitz definitions at 4 years, respectively. Mean (range) BCF-free rates were significantly higher for a PSA nadir ≤0.5 ng/mL and prostate volume ≤30 mL for both definitions at 4-year follow-up [Stuttgart: 79 (72-86)% vs. 25 (13-38)%; Horwitz: 82 (77-87)% vs. 33 (21-44)%] and [Stuttgart: 72 (64-79)% vs. 56 (42-69)%; Horwitz: 75 (69-80)% vs. 63 (53-74)%], respectively. Pre-treatment PSA and PSA nadir of >0.5 ng/mL were the predictors of BCF using both definitions. CONCLUSIONS: Primary HIFU appears to result in promising 4-year BCF-free rates in individuals with low- and intermediate-risk prostate cancer who achieve PSA nadir <0.5 ng/mL. A prostate volume <30 mL is associated with PSA nadir levels of <0.5 ng/mL suggesting a potential role for pretreatment volume reduction (medically or surgically) in larger prostates.

Pathophysiology of overactive bladder.

Overactive bladder (OAB) is a common disorder that negatively affects the quality of life of our patients and carries a large socioeconomic burden. According to the International Continence Society, it is characterized as urinary urgency, with or without urge incontinence, usually, with frequency and nocturia in the absence of causative infection. The pathophysiology of this disease entity varies between neurogenic, myogenic, or idiopathic factors. This paper provides a review of the contemporary theories behind the pathophysiology of OAB.

Pelvic electrical neuromodulation for the treatment of overactive bladder symptoms.

Overactive bladder syndrome negatively affects the daily life of many people. First-line conservative treatments, such as antimuscarinics, do not always lead to sufficient improvement of the complaints and/or are often associated with disabling adverse effects leading to treatment failure. Electrical stimulation of the sacral nerves has emerged as an alternative and attractive treatment for refractory cases of bladder overactivity. Few theories attempted to explain its mechanism of action which remains elusive. It involves percutaneous posterior tibial nerve stimulation and more commonly sacral neuromodulation. For the latter, temporary sacral nerve stimulation is the first step. If the test stimulation is successful, a permanent device is implanted. The procedure is safe and reversible. It carries a durable success rate. The technique should be combined with careful followup and attentive adjustments of the stimulation parameters in order to optimize the clinical outcomes. This paper provides a review on the indications, possible mechanisms of action, surgical aspects and possible complications, and safety issues of this technique. The efficacy of the technique is also addressed.

Efficacy of sacral neuromodulation in treatment of bladder pain syndrome: long-term follow-up.

AIMS: This study was sought to evaluate the efficacy and durability of sacral neuromodulation in the treatment of bladder pain syndrome (BPS) patients. METHODS: A retrospective chart review was performed of patients who had unilateral sacral nerve stimulator (InterStim®) for refractory BPS between June 2002 and December 2004. Patients were qualified for permanent implantation by showing ≥ 50% improvement in their bladder pain and voiding symptoms 1-week post-percutaneous nerve evaluation (PNE). Voiding diary was completed at pre-implantation, 1 year, and on the last visit. Urinary distress inventory short form was completed pre-implantation and on the last visit. Bladder pain was evaluated by visual analogue scale. Primary outcome was improvement in bladder pain. Differences among groups were compared by one-way ANOVA and t-test. Statistical significance was set at P ≤ 0.05. RESULTS: Twenty-one female patients diagnosed with BPS had PNE; 11 patients (52%) showed ≥ 50% improvement in their bladder pain and voiding symptoms and they consider candidates for permanent implantation (Table I), while 10 patients (48%) failed to show 50% improvement in their voiding symptoms or bladder pain (Table II). In those 11 patients who underwent permanent implantation, the average patient's age was 44.3 ± 8.9 years; average time since diagnosis was 3 ± 0.8 years; the average follow- up was 71.5 ± 9.3 months (Table III). There was significant improvement in the bladder pain and voiding parameters at 1-year follow-up, which was maintained at 5-year follow-up. There was continuous improvement in urgency (1.2 ± 0.68) at 1-year follow-up, and (0.98 ± 0.72) at the last visit. Average voided volume was also continuously improved from 242 ± 62.7 ml at 1-year follow-up to 276 ± 64.7 ml on the last visit. CONCLUSION: Sacral neuromodulation as part of multimodal treatment provides an effective long-term treatment option for sub-group of refractory BPS.

Mechanisms of action of sacral neuromodulation.

The lower urinary tract dysfunction encompasses voiding, postvoiding, and storage symptoms. Conventional treatment modalities include pharmacotherapy and behavioural therapy. Sacral neuromodulation (SNM) is a safe and minimally invasive treatment modality that has recently gained wide acceptance in the management of urinary urge incontinence, urge frequency, and nonobstructive urinary retention, in particular, among those patients with conditions refractory to conventional methods. We searched multiple electronic databases through June 30, 2009 for eligible studies. We examined published clinical and experimental studies concerning the mechanisms of action of SNM. In the first part of the manuscript, we describe the anatomy and functions of the lower urinary tract including the reflexes involved in its functions and then review the pathophysiology of major types of the lower urinary tract dysfunction. In the second part, we discuss different ways for SNM to control various types of voiding dysfunction. The lower urinary tract dysfunctions affect millions of people worldwide and have a severe impact on their quality of life. SNM offers a safe and minimally invasive modality in the treatment of voiding dysfunctions, especially in patients with conditions refractory to conventional therapies.

Effects of doxycycline on voiding behaviour of rats with bladder outlet obstruction.

OBJECTIVE: To examine the voiding behaviour changes in rats with bladder outlet obstruction (BOO) while inhibiting matrix metalloproteinase (MMP) activity with doxycycline, as increased MMP activity may be involved in obstruction-induced bladder hypertrophy. MATERIALS AND METHODS: Female Sprague-Dawley were divided into eight groups (three rats in each group): normal control (NC) +/- doxycycline, 3 weeks partial BOO (3WPBOO) +/- doxycycline, 6 weeks PBOO +/- doxycycline, and 3 weeks PBOO followed by 3 weeks de-obstruction (3WOD) +/- doxycycline. All rats received the same food and water and were on the same 12 h dark/light cycle housed in metabolic cages. Treatment groups were given doxycycline 15 mg/kg/day subcutaneously twice daily. The voiding variables measured were average voided volume (AV V) and voiding frequency (VF) in 24 h. After completion of the voiding behaviour studies, the rats were killed and their bladders were excised and weighed. RESULTS: The AV Vs were significantly increased (P < 0.05) in all study groups compared with the NC group except for the 3WPBOO-doxycycline and 3WOD-doxycycline groups. The VF was significantly increased (P < 0.05) only in the 3WOD-doxycycline group. The bladder weights were significantly increased after PBOO in all the study groups (P < 0.05), except for the 3WOD group. CONCLUSION: These data show that MMP inhibition may affect voiding behaviour during the response to BOO or its relief. This is the first clinical demonstration that interfering with a principal target of bladder muscle wall remodelling may have a direct effect on bladder function.

Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence.

OBJECTIVE: To evaluate the urodynamic data before and 6 months after implantation of sacral neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and clinical efficacy in patients with UI. PATIENTS AND METHODS: In all, 111 patients with a >50% reduction in UI symptoms during a percutaneous nerve evaluation test qualified for surgical implantation of SNM. Patients were categorized in two subgroups, i.e. those with UI with or without confirmed detrusor overactivity (DO) at baseline. At the 6-month follow-up all patients had a second urodynamic investigation, with the stimulator switched on. RESULTS: At baseline, there was urodynamically confirmed DO in 67 patients, while 44 showed no DO. A review of filling cystometry variables showed a statistically significant improvement in bladder volumes at first sensation of filling (FSF) and at maximum fill volume (MFV) before voiding for both UI subgroups, compared with baseline. In 51% of the patients with UI and DO at baseline, the DO resolved during the follow-up. However, those patients were no more clinically successful than those who still had DO (P = 0.73). At the 6-month follow-up, 55 of 84 implanted patients showed clinical benefit, having a >or=50% improvement in primary voiding diary variables. Patients with UI but no DO had a higher rate of clinical success (73%) than patients with UI and DO (61%), but the difference was not statistically significant. CONCLUSION: These urodynamic results show a statistically significant improvement in FSF and MFV in patients with UI with or with no DO after SNM. Although there was a urodynamic and clinical improvement in both groups, patients with UI but no DO are at least as successful as patients with UI and DO. Therefore in patients with UI, DO should not be a prerequisite selection criterion for using SNM.

Results of sacral neuromodulation therapy for urinary voiding dysfunction: outcomes of a prospective, worldwide clinical study.

PURPOSE: This 5-year, prospective, multicenter trial evaluated the long-term safety and efficacy of sacral neuromodulation in patients with refractory urge incontinence, urgency frequency and retention. MATERIALS AND METHODS: A total of 17 centers worldwide enrolled 163 patients (87% female). Following test stimulation 11 patients declined implantation and 152 underwent implantation using InterStim. Of those treated with implantation 96 (63.2%) had urge incontinence, 25 (16.4%) had urgency frequency and 31 (20.4%) had retention. Voiding diaries were collected annually for 5 years. Clinical success was defined as 50% or greater improvement from baseline in primary voiding diary variable(s). RESULTS: Data for all implanted cases were reported. For patients with urge incontinence mean leaking episodes per day decreased from 9.6 +/- 6.0 to 3.9 +/- 4.0 at 5 years. For patients with urgency frequency mean voids per day decreased from 19.3 +/- 7.0 to 14.8 +/- 7.6, and mean volume voided per void increased from 92.3 +/- 52.8 to 165.2 +/- 147.7 ml. For patients with retention the mean volume per catheterization decreased from 379.9 +/- 183.8 to 109.2 +/- 184.3 ml, and the mean number of catheterizations decreased from 5.3 +/- 2.8 to 1.9 +/- 2.8. All changes were statistically significant (p <0.001). No life threatening or irreversible adverse events occurred. In 102 patients 279 device or therapy related adverse events were observed. At 5 years after implantation 68% of patients with urge incontinence, 56% with urgency frequency and 71% with retention had successful outcomes. CONCLUSIONS: This long-term study demonstrates that InterStim therapy is safe and effective for restoring voiding in appropriately selected cases refractory to other forms of treatment.

Early versus late treatment of voiding dysfunction with pelvic neuromodulation.

INTRODUCTION: Pelvic neuromodulation is an established method of treating voiding dysfunction. Little is known about the pathophysiology associated with voiding dysfunction. Reports have suggested that a delay in treating patients with sacral neuromodulation therapy can impact the success rate of this type of treatment in voiding dysfunction. We examined patient response to pelvic neuromodulation when it was applied early versus late in the postdiagnosis of voiding dysfunction. METHODS: We conducted a retrospective study of 42 patients (38 women and 4 men) with voiding dysfunction who underwent surgery for implant with the Interstim (Medtronic, Minneapolis, Minn.). Prior to implantation, patients were required to pass a percutaneous nerve evaluation (PNE) over a 1-week period. Patients were observed for 20-48 months postimplantation. All patients recorded their voiding parameters at baseline, after screening and every 6 months thereafter. Twenty patients (in the early group) underwent implant surgery with the neurostimulator 2-4 weeks post-PNE, and 22 patients (the late group) had the device implanted 6-24 months post-PNE owing to local logistical circumstances. RESULTS: In the early group, 16 of 20 patients (80%) maintained a good response. In the late group, 13 of 22 (59%) patients showed a good response. Groups were well matched in terms of age, duration of voiding dysfunction and incidence of comorbidity. CONCLUSION: Patients who were delayed more than 6 months in receiving the neurostimulator implant showed a worse response than did patients who had the device implanted soon after PNE. This indicates the possibility of disease progression, which may limit the response to sacral neuromodulation.

Safety of MRI at 1.5Tesla in patients with implanted sacral nerve neurostimulator.

OBJECTIVES: Sacral neuromodulation has become an established method to treat voiding dysfunction. Currently the use of implanted sacral nerve stimulators is becoming more popular worldwide. Magnetic resonance imaging (MRI) is an important diagnostic tool for many medical and neurological disorders. Many radiology centers do not perform MRI examinations on patients with implanted sacral nerve stimulator. The basis for this policy is that potential hazards such as motion, dislocation or torquing of the implanted pulse generator (IPG), heating of the leads, and damage to the IPG may occur, resulting in painful stimulation. In contrast, many studies conducted on MRI at 1.5Tesla in patients with implantable devices have found the examination to be safe if the area to be imaged is out of the isocenter of the MRI scanner and other precautions are taken. METHODS: Eight MRI examinations at 1.5Tesla were conducted in areas outside the pelvis on six patients with implanted sacral nerve stimulator (InterStim neurostimulator; Medtronic, Inc, Minneapolis, MN, USA). Implanted pulse generators were examined before and after MRI procedures. All patients had their parameters recorded; then the IPGs were put to "nominal" status. Patients were monitored continuously during and after the procedure. After the MRI session, the site of the implanted device was examined and changes were reported. Devices were then re-programmed to their previous setup with the use of a programmer (model 7432; Medtronic, Inc). Voiding diaries were collected after MRI procedures and compared with previous records. RESULTS AND CONCLUSION: During the MRI session, no patient showed symptoms that required stopping the examination. There was no change in perception of the stimulation after re-programming of the implanted sacral nerve stimulator, according to patients' feedback. Devices were functioning properly, and no change in bladder functions was reported after MRI examinations. Finally, we hope that presenting these cases will encourage performance of more comprehensive studies on implanted sacral nerve stimulators on a larger patient population in the near future.

Canadian experience in sacral neuromodulation.

The application of sacral nerve modulation and stimulation has gained wide acceptance asa tool to enhance the control of voiding. The simplicity of the technique has made the therapy appealing for refractory cases of voiding dysfunction. The percutaneous screening test is mandatory for the success of the therapy. Long-term follow-ups have shown efficacy and safety inpatients with voiding dysfunction. Sacral nerve modulation is an effective modality in the treatment of various voiding and storage dysfunction. The tined lead offers a minimally invasive implant procedure. The simplicity of the procedure and the patient's sensory awareness help to ensure best lead placement. Furthermore, local anesthesia instead of general anesthesia allows faster patient recovery and reduces complications. Finally, sacral neuromodulation offers a modality in the management of patients with voiding dysfunction.

Change of vanilloid receptor 1 following neuromodulation in rats with spinal cord injury.

BACKGROUND: Neuromodulation has been used to treat voiding dysfunction caused by spinal cord injury (SCI). However, the underlying mechanism of this technique is not well understood. Recently, vanilloid receptor 1 (VR1) has been recognized as a capsaicin receptor and an agent for noxious stimuli. The purposes of this study were to evaluate whether development of bladder hyperreflexia after SCI involves VR1 upregulation and whether VR1 is involved in the process of neuromodulation. MATERIALS AND METHODS: Sprague-Dawley rats (n = 20) were divided into five groups: sham control (n = 4); 3 days after SCI (n = 4); 7 days after SCI (n = 4); 14 days after SCI (n = 4), and 14 days after SCI with neurostimulation (n = 4). Bilateral electrode wires were implanted into S1 dorsal foramina and electrical stimulation was performed 8 h/day for 2 weeks. Spinal segments of L6, S1, and dorsal root ganglia were removed and cut into sections. The intensity of VR1 staining was evaluated by image analysis. RESULTS: VR1-positive staining was confined to the superficial dorsal horn of the spinal cord. The staining was weak in the sham group (1/luminosity: 0.0050 +/- 0.0006), but the staining intensity was significantly increased in three SCI groups (3 days, 7 days, and 14 days) when compared with that in the sham group (P < 0.05). After neuromodulation, the staining intensity was reduced. CONCLUSIONS: VR1 expression in the spinal cord is up-regulated after SCI. Sacral nerve root stimulation can down-regulate the VR1 expression.