The impact of scrambler therapy on pain and quality of life for chemotherapy-induced peripheral neuropathy: A pilot study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating disturbance among patients who received chemotherapy, with no effective treatment available. Scrambler therapy (ST) is a noninvasive treatment capable of improving multiple quality-of-life symptoms beyond pain. We aimed to evaluate the efficacy of ST for pain and nonpain symptoms related to CIPN. METHODS: Ten patients with moderate to severe CIPN symptoms for >3 months were enrolled in a single-arm trial of ST for 10 daily sessions. CIPN-related symptoms were measured throughout the treatment period and up to 6 months thereafter. RESULTS: The worst pain was reduced by 6 months (p = 0.0039). QST demonstrated the greatest improvement in pressure of 60 g (p = 0.308, Cohen's d = 0.42) and cold temperature threshold of 2.5°C (p = 0.9375, Cohen's d = 0.51) in the gastrocnemius area. Symptoms of numbness, tingling, trouble walking, and disturbed sleep had significant improvements at 6 months. Pain medication use decreased by 70% at the end of treatment and by 42% at 6 months. Patient satisfaction was high (82%) and no adverse events with ST treatment were reported. CONCLUSIONS: The results of this pilot trial support the use of ST by demonstrating improvement in multiple domains of quality of life for CIPN patients during an extended follow-up of 6 months. However, further large-scale studies are needed to confirm our findings.

Safety of Scrambler Therapy: A Systematic Review of Complications and Adverse Effects.

OBJECTIVE: The objective was to qualitatively synthesize all reported cases of complications, adverse effects, side effects, or harms arising from the use of scrambler therapy (ST). METHODS AND DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Embase, Scopus, Web of Science, United States National Library of Medicine clinical trials registry, and Cochrane Central Register of Controlled Trials databases were searched from database inception to December 10, 2021. Case reports/series, abstracts, retrospective studies, and prospective studies (e.g., open-label trials, randomized controlled trials) pertaining to ST and any description of a complication, adverse effect, side effect, or harm were screened. The search protocol was developed a priori and registered via the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021291838). RESULTS: A total of six RCTs, 19 prospective open-label trials, and 11 case series / case reports met the inclusion criteria, comprising 1,152 total patients. Two patients experienced contact dermatitis, and one patient reported minor ecchymosis that resolved without intervention. This yielded a composite complication rate of 0.26% (3/1,152). There were zero reported serious adverse events. CONCLUSIONS: When used in accordance with the treatment protocols described by the United States Food and Drug Administration and device manual, ST is associated with a reported composite complication rate that is orders of magnitude lower than those of invasive neuromodulation devices. ST neuromodulation is a safe alternative for patients who cannot undergo invasive neuromodulation device implantation because of either risk or preference.

Scrambler Therapy Enhances Quality of Life in Cancer Patients in a Palliative Care Setting: A Randomised Controlled Trial.

Objectives: Given the known side effects of opioids and the negative impact of these side effects on quality of life (QOL), there is a need for therapies that can reduce opioid intake and improve QOL in patients suffering from cancer pain. Scrambler therapy (ST) is a neuromodulatory therapy that has been shown to reduce cancer pain, but its effect on QOL is not well understood. This study intended to evaluate the efficacy of ST for enhancing QOL in cancer patients through minimising pain and opioid intake. Material and Methods: This was a randomised controlled trial including 80 patients with head, neck and thoracic cancer. In both arms, patients were given pain management drugs following the WHO analgesic ladder for ten consecutive days. In the intervention arm each day ST was given. Pain, morphine intake, and QOL (WHOQOL-BREF) were assessed. Results: All domains of QOL improved significantly in the intervention arm in comparison to the control arm. In comparison to baseline, pain improved in both the intervention and the control arm on day 10 and at follow-up. However, QOL significantly improved in the intervention arm, while morphine intake decreased. In the control arm, QOL deteriorated, while morphine intake increased. Conclusion: ST significantly improved QOL. Since the increase in QOL took place along with a significantly lower morphine intake, the improvement in QOL may not only be explained by lower pain scores but, also, by a reduced intake of morphine, because the lower dosages of morphine will decrease the likelihood of side effects associated with the drug.

Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, in need of effective treatment. Preliminary data support the efficacy of scrambler therapy (ST), a noninvasive cutaneous electrostimulation device, in adults with CIPN. We test the efficacy, safety, and durability of ST for neuropathic pain in adolescents with CIPN. PATIENTS AND METHODS: We studied nine pediatric patients with cancer and CIPN who received ST for pain control. Each patient received 45-min daily sessions for 10 consecutive days as a first step, but some of them required additional treatment. RESULTS: Pain significantly improved comparing Numeric Rate Scale after 10 days of ST (9.22 ± 0.83 vs. 2.33 ± 2.34; P < 0.001) and at the end of the optimized cycle (EOC) (9.22 ± 0.83 vs. 0.11 ± 0.33, P < 0.001). The improvement in quality of life was significantly reached on pain interference with general activity (8.67 ± 1.66 vs. 3.33 ± 2.12, P < 0.0001), mood (8.33 ± 3.32 vs. 2.78 ± 2.82, P < 0.0005), walking ability (10.00 vs. 2.78 ± 1.22, P < 0.0001), sleep (7.56 ± 2.24 vs. 2.67 ± 1.41, P < 0.001), and relations with people (7.89 ± 2.03 vs. 2.11 ± 2.03, P < 0.0002; Lansky score 26.7 ± 13.2 vs. 10 days of ST 57.8 ± 13.9, P < 0.001; 26.7 ± 13.2 vs. EOC 71.1 ± 16.2, P < 0.001). CONCLUSION: Based on these preliminary data, ST could be a good choice for adolescents with CIPN for whom pain control is difficult. ST caused total relief or dramatic reduction in CIPN pain and an improvement in quality of life, durable in follow-up. It caused no detected side effects, and can be retrained successfully. Further larger studies should be performed to confirm our promising preliminary data in pediatric patients with cancer.

Efficacy of scrambler therapy on breast cancer-related lymphedema.

[Purpose] This study aimed to determine the effect of scrambler therapy on upper extremity pain in patient who had undergone breast cancer related lymphedema. [Participant and Methods] The patient was a 39-year-old woman who developed pain and lymphedema in the right upper extremity after mastectomy. Scrambler therapy was administered once a day every 45 minutes for 10 days to patient. [Results] After 10 sessions of scrambler therapy, pain was reduced 6 points. Bioimpedence and circumference was not increased after 10 treatment sessions. [Conclusion] Thus, scrambler therapy reduced pain without increased lymphedema.

Effects of scrambler therapy on pain and depression of patients with chronic low back pain: case study.

[Purpose] This study was designed to investigate the effect of scrambler therapy on the pain and depression of patients with chronic low back pain. [Subject and Methods] Applied scrambler therapy to a 52 year-old man who was diagnosed with chronic low back pain, for 40 minutes once a day during the 10-day execution. Pain and depression were measured using the visual analogue scale and the Beck Depression Inventory. [Results] According to the measurement results, pain and depression decreased after ten sessions of scramble therapy. [Conclusion] Scrambler therapy shows positive effects on pain and depression of patients with chronic low back pain.

The effects of pain scrambler therapy on the pain and quality of life of degenerative gonarthritis patients.

[Purpose] The purpose of this study was to identify the effects of pain scrambler therapy on the pain and quality of life of degenerative gonarthritis patients. [Subject and Methods] This study is a single case study. Pain scrambler therapy was applied for 40 minutes per session once a day for 15 days to a 62-year-old female patient diagnosed with degenerative gonarthritis. Pain was measured using the Visual Analogue Scale and quality of life was measured using the short form-36 item after therapy. [Results] Decrease in pain and improved quality of life were evident after pain scrambler therapy. [Conclusion] Pain scrambler therapy had a potential to decrease pain and improve the quality of life in degenerative gonarthritis patients.

Impact of Scrambler Therapy on Pain Management and Quality of Life in Cancer Patients: A Study of Twenty Cases.

AIM OF THE STUDY: To study the effect of scrambler therapy on patients with chronic cancer pain. MATERIALS AND METHODS: This is a prospective, observational study conducted on patients with chronic pain due to malignancy which is not responding to oral analgesics. A total of twenty patients were included in the study (ten males, ten females) with a visual analog scale score of >4 on oral analgesics. Patients aged 18-70 years with a life expectancy of >3 months having bony, neuropathic, or mixed type of pain were included in the study. A total of 12 sessions of scrambler therapy were planned, ten sessions on consecutive days and one session each on two follow-up visits after 1 week each. Each session lasted for 40 min. Pain relief and quality of life according to the World Health Organization Quality of Life were recorded as primary outcome variables. RESULTS: All patients had good pain relief and improvement in all four domains of quality of life. Pain scores decreased significantly (P < 0.01) after each session and at each follow-up. Patients showed significant improvement in physical, psychological, social, and environmental health (P < 0.01) after the therapy. CONCLUSION: Scrambler therapy offers a promising role in the pain physician's armamentarium as an adjunct to pharmacological therapy for the treatment of chronic drug-resistant cancer pain; it may bring down analgesic drug requirements significantly and improve quality of life in cancer patients. Larger prospective, randomized multicenter studies are needed to validate the findings of the small pilot studies published in literature so far.

Scrambler Therapy for the management of chronic pain.

PURPOSE: Chronic pain is a widespread and debilitating condition, encountered by physicians in a variety of practice settings. Although many pharmacologic and behavioral strategies exist for the management of this condition, treatment is often unsatisfactory. Scrambler Therapy is a novel, non-invasive pain modifying technique that utilizes trans-cutaneous electrical stimulation of pain fibers with the intent of re-organizing maladaptive signaling pathways. This review was conducted to further evaluate what is known regarding the mechanisms and mechanics of Scrambler Therapy and to investigate the preliminary data pertaining to the efficacy of this treatment modality. METHODS: The PubMed/Medline, SCOPUS, EMBASE, and Google Scholar databases were searched for all articles published on Scrambler Therapy prior to November 2015. All case studies and clinical trials were evaluated and reported in a descriptive manner. RESULTS: To date, 20 reports, of varying scientific quality, have been published regarding this device; all but one small study, published only as an abstract, provided results that appear positive. CONCLUSION: The positive findings from preliminary studies with Scrambler Therapy support that this device provides benefit for patients with refractory pain syndromes. Larger, randomized studies are required to further evaluate the efficacy of this approach.

Pilot evaluation of scrambler therapy for pain induced by bone and visceral metastases and refractory to standard therapies.

PURPOSE: Scrambler therapy is a non-invasive neurocutaneous electrical pain intervention, effective for the treatment of neuropathic pain. Currently, few data about the efficacy of this treatment in cancer pain induced by skeletal and visceral metastases are available. The aim of this single-center case series is to evaluate the efficacy of scrambler therapy in reducing this kind of cancer pain after failure of standard treatments, including pharmacological therapies and radiation therapy. METHODS: Twenty-five consecutive patients underwent scrambler therapy individually delivered by MC5-A Calmare for 10 daily sessions each of 30-40 min. Pain was measured by a numeric rating scale at baseline, as well as before and after each treatment session. RESULTS: One hundred percent of patients reached a pain relief ≥50 %. Pain score was reduced from 8.4 at baseline to 2.9 after treatment, with a mean pain relief of 89 %. The sleeping hours improved from 4.4 ± 1.2 to 7.5 ± 1.1. The duration of pain control by scrambler therapy was 7.7 ± 5.3 weeks. No adverse events were observed. CONCLUSION: Scrambler therapy does not present toxicity and allows opioids dosage reduction, and it is also a repeatable treatment. Present novel data support that scrambler therapy seems to be effective for the treatment of cancer pain. Further evaluation in randomized and controlled clinical trials should be performed to confirm our findings.

Scrambler Therapy(®) MC-5A for Complex Regional Pain Syndrome: Case Reports.

BACKGROUND: Complex regional pain syndrome (CRPS) is a disorder that is often challenging to treat and can be associated with a prolonged course of severe pain. Therapy of CRPS remains controversial; the pain often can be very difficult to control, and treatment includes medications, physical therapy, regional anesthesia, and neuromodulation. AIM: We evaluated Scrambler Therapy(®) (ST) in terms of efficacy, safety, and durability of treatment effect in patients suffering from CRPS. MATERIALS AND METHODS: We report the response to ST in four patients with CRPS referred to the Pain Center of Bambino Gesù Children's Hospital. The patients previously did not respond to conventional and nonconventional medical treatments. RESULTS: The treatment with ST was found effective in all four of our patients; they obtained pain relief for long periods and an improvement in their quality of life. We observed a progressive improvement with complete disappearance of neuropathic pain. Patients also reported a muscle strength increase that allowed them to resume normal daily activities. DISCUSSION AND CONCLUSION: We conclude that ST may offer a therapeutic opportunity for patients with neuropathic pain resulting from CRPS, without side effects and with minimal discomfort during treatment. The observed pain relief indicates that ST could be an effective option for such patients.

Unraveling the Potential of Electroanalgesia: A Literature Review of Current Therapeutics.

Neuropathic pain (NP), arising from dysfunction in the neurological system, poses a significant challenge in pain management due to its intricate origin and unpredictable response to conventional treatments. Electroanalgesia, a collection of techniques such as transcutaneous electric nerve stimulation (TENS), peripheral electrical nerve stimulation (PENS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and electroacupuncture (EA), presents a potential alternative or complementary approach. This review brings together evidence from 56 studies to evaluate the effectiveness and safety of electroanalgesia in chronic NP. It discusses the mechanisms underlying NP, the indications for electroanalgesia, and the techniques utilized, emphasizing the diverse applications and potential benefits. However, despite its potential uses, electroanalgesia has its limitations, including variable effectiveness and potential adverse effects. Furthermore, the review recognizes the limitations of the methodology and the need for further research to refine treatment protocols and enhance the understanding of electroanalgesia's role in comprehensive pain management strategies.

Scrambler Therapy for Patients With Complex Regional Pain Syndrome: A Case Series.

Complex regional pain syndrome is a chronic debilitating pain disorder that is difficult to manage, in part due to its heterogeneous clinical presentation and lack of clearly defined pathophysiology. Patients usually require a multidisciplinary approach to treatment, which can entail pharmacotherapy, physical therapy, behavioral therapy, and interventional pain procedures, such as sympathetic nerve blocks, spinal cord stimulation, and dorsal root ganglion stimulation. However, many patients continue to experience pain refractory to these multimodal strategies. Scrambler therapy (ST) is a noninvasive method of neuromodulation that is applied through cutaneous electrodes, and can alleviate chronic neuropathic pain by stimulating C-fibers and replacing endogenous pain signals with synthetic non-nociceptive signals. Although the use of ST has been reported for several types of refractory central and peripheral neuropathic pain, there is a paucity of data regarding the use of ST for complex regional pain syndrome. We present two patients with complex regional pain syndrome of the right lower extremity, who each underwent ST and experienced significant pain relief and improvement in function and quality of life.

Scrambler Therapy for the Treatment of Pain in Schwannomatosis.

Schwannomatosis patients (SP) suffer from chronic nerve pain that is often inadequately relieved. Scrambler therapy (ST) can relieve neuropathic pain quickly, safely, and inexpensively. We successfully treated a patient who had disabling leg pain with five daily sessions of ST, each for 40 minutes. She had complete relief of pain and hyperalgesia, with return to normal function, by day 5, that has persisted for at least three weeks. This article briefly describes Schwannomatosis, scrambler therapy, and the need for further research to ascertain the best way to use this neuromodulation.

Successful Treatment of Paraneoplastic Neuropathy and Pruritis With Scrambler Therapy: A Case Report.

Paraneoplastic neuropathy, including pruritis, remains a vexing problem as it often does not resolve even with successful treatment of cancer. Scrambler Therapy is a superficial form of neuromodulation that replaces the pain signal with "non-pain information" that is approved for chronic and neuropathic pain, with few side effects. We report here two cases of paraneoplastic neuropathy, one with additional pruritis, that both responded satisfactorily to Scrambler Therapy with no side effects.

Scrambler Therapy for Chronic Pain after Burns and Its Effect on the Cerebral Pain Network: A Prospective, Double-Blinded, Randomized Controlled Trial.

Chronic pain is common after burn injuries, and post-burn neuropathic pain is the most important complication that is difficult to treat. Scrambler therapy (ST) is a non-invasive modality that uses patient-specific electrocutaneous nerve stimulation and is an effective treatment for many chronic pain disorders. This study used magnetic resonance imaging (MRI) to evaluate the pain network-related mechanisms that underlie the clinical effect of ST in patients with chronic burn-related pain. This prospective, double-blinded, randomized controlled trial (ClinicalTrials.gov: NCT03865693) enrolled 43 patients who were experiencing chronic neuropathic pain after unilateral burn injuries. The patients had moderate or greater chronic pain (a visual analogue scale (VAS) score of ≥5), despite treatment using gabapentin and other physical modalities, and were randomized 1:1 to receive real or sham ST sessions. The ST was performed using the MC5-A Calmare device for ten 45 min sessions (Monday to Friday for 2 weeks). Baseline and post-treatment parameters were evaluated subjectively using the VAS score for pain and the Hamilton Depression Rating Scale; MRI was performed to identify objective central nervous system changes by measuring the cerebral blood volume (CBV). After 10 ST sessions (two weeks), the treatment group exhibited a significant reduction in pain relative to the sham group. Furthermore, relative to the pre-ST findings, the post-ST MRI evaluations revealed significantly decreased CBV in the orbito-frontal gyrus, middle frontal gyrus, superior frontal gyrus, and gyrus rectus. In addition, the CBV was increased in the precentral gyrus and postcentral gyrus of the hemisphere associated with the burned limb in the ST group, as compared with the CBV of the sham group. Thus, a clinical effect from ST on burn pain was observed after 2 weeks, and a potential mechanism for the treatment effect was identified. These findings suggest that ST may be an alternative strategy for managing chronic pain in burn patients.

Efficacy of Scrambler Therapy for Management of Chronic Pain: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although several randomized controlled trials (RCTs) have reported the efficacy of scrambler therapy (ST) for the management of chronic pain, those findings remain inconsistent. OBJECTIVES: This meta-analysis aimed to investigate the efficacy of ST for the management of chronic pain. STUDY DESIGN: A meta-analysis of RCTs. METHODS: We searched core databases including PubMed, EMBASE, and the Cochrane library for RCTs in October 2021. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) for pain reduction were calculated using a random-effects model meta-analysis. RESULTS: Out of 348 studies, a total of 7 RCTs (n = 287 patients) that met the inclusion criteria were included in the final analysis. Overall, ST marginally decreased pain scores after the end of the treatment compared with the control group, with substantial heterogeneity (SMD, -0.85; 95% CI, -1.66 to -0.03; I2 = 89.5%, n = 7). A subgroup meta-analysis found that the use of ST significantly reduced analgesic consumption compared to the control group (SMD, -0.54; 95% CI, -0.93 to -0.14; I2 = 0.0%; n = 2). However, no significant efficacy was observed in the subgroup meta-analyses by methodological quality, type of diseases causing pain, and follow-up period. LIMITATIONS: The included trials have a small sample size and low methodological quality. CONCLUSIONS: ST seems to be effective in the management of patients with chronic pain. However, further, large RCTs are warranted to confirm our findings.

Looking beyond the obvious: Role of non-invasive electroanalgesia in management of cancer pain.

Pain is considered as one of the most debilitating symptoms of cancer and its treatment. Owing to the limited efficacy of traditional pharmacological interventions to address cancer pain in its entirety, an avenue exists for exploration into nonpharmacological therapies. Analgesia using non-invasive electrotherapeutic modalities such as transcutaneous electrical nerve stimulation (TENS) and scrambler therapy emerges as a viable option to address cancer pain. The inability of these modalities to find a place within the recommended clinical guidelines has possibly resulted in the paucity of application of the same within the clinical setup. This perspective article aims at stimulating a discussion surrounding the inclusion of non-invasive neuromodulatory treatment techniques such as TENS and scrambler therapy to combat cancer pain and explore the benefits and pitfalls of using these techniques as an adjunct to the pre-existing treatment strategies. It is envisioned that this opinion piece will open a dialogue about a possible home for non-invasive electroanalgesia within the clinical treatment pathway for cancer pain.

Painful Diabetic Neuropathy - Spinal Cord Stimulation, Peripheral Nerve Stimulation, Transcutaneous Electrical Nerve Stimulation, and Scrambler Therapy: A Narrative Review.

BACKGROUND: First-line medications for the treatment of painful diabetic neuropathy (PDN) are associated with a substantial rate of discontinuation due to adverse effects or insufficient efficacy. Neuromodulation techniques have been used for PDN, but a comprehensive review of the literature that incorporates several distinct device categories has yet to be undertaken. OBJECTIVES: We aimed to summarize the evidence regarding 4 major types of neuromodulation devices for the treatment of PDN. We focused on spinal cord stimulators (SCS), peripheral nerve stimulators (PNS), transcutaneous electrical nerve stimulators (TENS), and scrambler therapy devices (ST) because they are often used for refractory neuropathic pain. STUDY DESIGN: Narrative Review. METHODS: A comprehensive and reproducible literature search was performed using PubMed with no search restrictions applied. The available Medical Subject Headings were used. Inclusion criteria included prospective studies, retrospective studies, case series, and case reports indexed from database inception to the search date (September 14, 2021). RESULTS: Seventeen studies met inclusion criteria, 10 of which were regarding SCS. Only 3 of the 10 were randomized controlled trials. We found no studies assessing contemporary PNS. Four studies assessed TENS, but the devices varied widely in voltages and waveforms. Two case reports described ST. LIMITATIONS: Potential selection bias due to the nature of a narrative review, although a reproducible search strategy was utilized. Several neuromodulation modalities have minimal published evidence available. CONCLUSIONS: The evidence for neuromodulation devices for the treatment of PDN mostly comprises open-label prospective trials or case reports. SCS has the most volume of evidence for efficacy. Studies regarding TENS show mixed results, possibly due to numerous device varieties. PNS and ST may hold promise based on their proposed mechanisms of action, but prospective controlled trials are needed.

Use of Scrambler Therapy in the Treatment of Amyloidosis Neuropathic Pain.

Background: Scrambler therapy (ST) is a relatively new neuromodulation technique that is useful in treatment of medication-resistant pain syndromes, including chemotherapy-induced peripheral neuropathy and other chronic pain syndromes. Amyloidosis commonly leads to peripheral neuropathy, and although the mechanism is unclear, it is possibly related to amyloid deposits on the nerve. Case Presentation: In this case presentation, we describe the novel use of ST for a patient with 13 years of neuropathic pain related to amyloidosis and worsened by chemotherapy. The patient reported bilateral hand pain with burning and aching and bilateral numbness on the soles of her feet. Her upper extremities were treated with 4 days of 40 minute ST treatment sessions providing reduction in her pain scores to zero. Discussion: Current therapy for amyloid peripheral neuropathy aims at treating the underlying condition, and then medical management with gabapentinoids. This is first case presentation showing successful treatment with ST.