10 kHz SCS therapy for chronic pain, effects on opioid usage: Post hoc analysis of data from two prospective studies.

Chronic pain, including chronic low back and leg pain are prominent causes of disability worldwide. While patient management aims to reduce pain and improve daily function, prescription of opioids remains widespread despite significant adverse effects. This study pooled data from two large prospective trials on 10 kHz spinal cord stimulation (10 kHz SCS) in subjects with chronic low back pain and/or leg pain and performed post hoc analysis on changes in opioid dosage 12 months post 10 kHz SCS treatment. Patient-reported back and leg pain using the visual analog scale (VAS) and opioid dose (milligrams morphine equivalent/day, MME/day) were compared at 12 months post-10 kHz SCS therapy to baseline. Results showed that in the combined dataset, 39.3% of subjects were taking >90 MME dose of opioids at baseline compared to 23.0% at 12 months post-10 kHz SCS therapy (p = 0.007). The average dose of opioids in >90 MME group was significantly reduced by 46% following 10 kHz SCS therapy (p < 0.001), which was paralleled by significant pain relief (P < 0.001). In conclusion, current analysis demonstrates the benefits of 10 kHz SCS therapy and offers an evidence-based, non-pharmaceutical alternative to opioid therapy and/or an adjunctive therapy to facilitate opioid dose reduction whilst delivering significant pain relief. Healthcare providers involved in management of chronic non-cancer pain can include reduction or elimination of opioid use as part of treatment plan when contemplating 10 kHz SCS.

Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP).

OBJECTIVES: Phantom limb pain (PLP) is a neuropathic condition in which pain is perceived as arising from an amputated limb. PLP is distinct from, although associated with, pain in the residual limb and nonpainful phantom sensations of the missing limb. Its treatment is extremely challenging; pharmaceutical options, while commonly employed, may be insufficient or intolerable. Neuromodulatory interventions such as spinal cord stimulation have generated mixed results and may be limited by poor somatotopic specificity. It was theorized that dorsal root ganglion (DRG) neuromodulation may be more effective. MATERIALS AND METHODS: Patients trialed a DRG neurostimulation system for their PLP and were subsequently implanted if results were positive. Retrospective chart review was completed, including pain ratings on a 100-mm visual analogue scale (VAS) and patient-reported outcomes. RESULTS: Across eight patients, the average baseline pain rating was 85.5 mm. At follow-up (mean of 14.4 months), pain was rated at 43.5 mm. Subjective ratings of quality of life and functional capacity improved. Some patients reduced or eliminated pain medications. Patients reported precise concordance of the paresthesia with painful regions, including in their phantom limbs; in one case, stimulation eliminated PLP as well as nonpainful phantom sensations. Three patients experienced a diminution of pain relief, despite good initial outcomes. CONCLUSIONS: DRG neuromodulation may be an effective tool in treating this pain etiology. Clinical outcomes in this report support recent converging evidence suggesting that the DRG may be the site of PLP generation and/or maintenance. Further research is warranted to elucidate mechanisms and optimal treatment pathways.

Bladder inhibition by intermittent pudendal nerve stimulation in cat using transdermal amplitude-modulated signal (TAMS).

AIMS: To determine if intermittent stimulation of the pudendal nerve using a transcutaneous stimulation method can inhibit reflex bladder activity. Intermittent stimulation consumes less electrical power than continuous stimulation, requiring a smaller battery and reducing the size of the stimulator for neuromodulation therapy. METHODS: A non-invasive stimulation method employing a transdermal amplitude-modulated signal (TAMS) was used in 18 α-chloralose anesthetized cats to stimulate the pudendal nerve via electrodes attached to the skin surface. Intermittent stimulation of different duty cycles was applied during repeated cystometrograms (CMGs) to inhibit reflex bladder activity. The bladder capacity measured during each CMG was used to indicate the inhibitory effect induced by the stimulation. RESULTS: Continuous stimulation maximally increased bladder capacity to 172.6 ± 15% of the control capacity, while intermittent stimulation at the duty cycles of 30/30, 5/5, and 1/1 ("on/off" in seconds) significantly (P < 0.05) increased bladder capacity to 132 ± 7.5%, 154.2 ± 20%, and 165.5 ± 28%, respectively. The inhibitory effect was gradually reduced as the "on/off" ratio was decreased. CONCLUSIONS: This pre-clinical study indicated that intermittent stimulation of the pudendal nerve could be as effective as continuous stimulation to inhibit reflex bladder activity. These results are useful for the design and development of new stimulator technology to treat overactive bladder, and are also important for understanding pudendal neuromodulation therapy.

A systematic review of clinical studies of electrical stimulation for treatment of lower urinary tract dysfunction.

INTRODUCTION AND HYPOTHESIS: The aim of this manuscript was to provide a systematic literature review of clinical trial evidence for a range of electrical stimulation therapies in the treatment of lower urinary tract symptoms (LUTS). METHODS: The databases MEDLINE, BIOSIS Previews, Inside Conferences, and EMBASE were searched. Original clinical studies with greater than 15 subjects were included. RESULTS: Seventy-three studies were included, representing implanted sacral nerve stimulation (SNS), percutaneous posterior tibial nerve stimulation (PTNS), and transcutaneous electrical stimulation (TENS) therapy modalities. CONCLUSIONS: Median mean reductions in incontinence episodes and voiding frequency were similar for implanted SNS and PTNS. However, long-term follow-up data to validate the sustained benefit of PTNS are lacking. Despite a substantial body of research devoted to SNS validation, it is not possible to definitively define the appropriate role of this therapy owing largely to study design flaws that inhibited rigorous intention to treat analyses for the majority of these studies.

Inhibition of bladder overactivity by stimulation of feline pudendal nerve using transdermal amplitude-modulated signal (TAMS).

OBJECTIVE: • To develop a non-invasive neuromodulation method targeting the pudendal nerve. MATERIALS AND METHODS: • Bladder overactivity induced by acetic acid (AA) irritation was partially suppressed by electrical stimulation of the pudendal nerve in α-chloralose anaesthetized cats using a transdermal amplitude-modulated signal (TAMS). RESULTS: • During cystometrography (CMG), intravesical infusion of 0.25% AA significantly decreased the mean (se) bladder capacity to 28.8 (5.9)% of the capacity measured during saline infusion. • The TAMS stimulation inhibited AA-induced bladder overactivity at 5, 7 and 10 Hz, and significantly increased the mean (se) bladder capacity to 61.8 (9.9)%, 51.3 (14.5)%, 53.6 (14.9)%, respectively, of the control capacity during saline infusion, whereas stimulation at 20-40 Hz had no effect. • Under isovolumetric conditions at a bladder volume ranging between 130 to 160% of the bladder capacity measured during AA infusion, TAMS stimulation at all frequencies (5-40 Hz) significantly suppressed the irritation-induced rhythmic bladder contractions, reduced the area under the bladder pressure curve, and decreased the frequency of bladder contractions. However, the amplitude of rhythmic bladder contractions was only significantly decreased at stimulation frequencies of 5-20 Hz. • At bladder volumes above the AA control capacity, TAMS stimulation with frequencies of 20-30 Hz had an excitatory effect, resulting in large amplitude (>25 cmH(2) O) bladder contractions. CONCLUSIONS: • TAMS stimulation targeting the cat pudendal nerve can inhibit C-fibre afferent-mediated bladder overactivity. • Thus, clinical research seems warranted to explore the usefulness of this technology for patients with overactive bladder symptoms.

Neuromodulation of bladder activity by stimulation of feline pudendal nerve using a transdermal amplitude modulated signal (TAMS).

AIM: To develop a non-invasive neuromodulation method to regulate bladder activity. METHODS: Neuromodulation of bladder activity was investigated in felines with an intact spinal cord under α-chloralose anesthesia using a transcutaneous stimulation method with surface electrodes attached to the skin area between the base of the tail and the sciatic notch. RESULTS: The bladder could be either inhibited or excited depending on stimulation frequency and bladder volume. With the bladder distended to induce large amplitude rhythmic isovolumetric bladder contractions, stimulation at a frequency between 5 and 7 Hz significantly suppressed the contractions. Stimulation applied during a cystometrogram (CMG) also increased bladder capacity by 44.3 ± 10.8%. At a frequency between 20 and 40 Hz the inhibitory effect on rhythmic bladder contractions was weak and did not increase bladder capacity during CMG. At low bladder volumes ranging between 60% and 100% of the bladder capacity 20 Hz stimulation-induced small amplitude (21.2 ± 14.6 cmH(2) O) bladder contractions. However, stimulation at 20 Hz induced large amplitude (111.7 ± 22.2 cmH(2) O) bladder contractions at a bladder volume about 100-110% of the bladder capacity after the rhythmic bladder contractions were completely inhibited by the inhibitory 5 Hz stimulation. CONCLUSIONS: Both inhibitory and excitatory effects on bladder activity can be obtained in cats using the non-invasive neural stimulation approach. This pre-clinical study warrants a further clinical trial to investigate the possibility of using this non-invasive stimulation method to treat incontinence or urinary retention.