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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Scrambler therapy for incident pain in bone metastases.

Incident pain, described as pain induced by bone metastasis and produced by movement, can be devastating. The high doses of opioids needed to control such pain may sedate the patient and cause additional complications. Treatment of incident pain with pharmaceuticals has rarely been studied; only eight patients have been reported in the literature who did not receive additional opioids. We present the case of a 69 year old man with shoulder destruction due to bone metastases who was able to use his arm for normal activities without pain after three sessions of scrambler therapy, a noninvasive form of electrical neuromodulation that requires further study.

Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis.

CONTEXT: Preliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN). OBJECTIVE: The objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler therapy vs. transcutaneous electrical nerve stimulation (TENS) in treating CIPN. METHODS: Fifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient-reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period. RESULTS: A 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) after crossover (P = 0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life. CONCLUSIONS: Similar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted.

The Efficacy of Scrambler Therapy for the Management of Head, Neck and Thoracic Cancer Pain: A Randomized Controlled Trial.

BACKGROUND: Pain is still a common feature in all types of cancers including head and neck and thoracic cancer. Neuromodulatory techniques have gained popularity over opioids in recent times because of the risks associated with chronic opioid therapy. There are no clinical trials evaluating the efficacy of scrambler therapy (ST) for the management of pain due to head and neck and thoracic cancer. OBJECTIVE: This trial was undertaken to evaluate the efficacy of scrambler therapy (ST) for pain relief and to assess the possible effect of ST on the dosage of opioids in patients suffering from cancer pain. STUDY DESIGN: A randomized control trial (RCT) was performed. SETTING: The trial was conducted at the Pain and Palliative Care Unit of the Dr. B.R. Ambedkar Institute Rotary Cancer Hospital of All India Institute of Medical Sciences, New Delhi, India. METHOD: Forty patients were included in each of the 2 arms, control and Intervention. In both arms, patients were given pain management drugs. In the intervention group, patients additionally received 10 consecutive sessions of ST with one follow-up after 7 days. A numeric rating scale (NRS-11) was used to measure pain. Drug dosage was also recorded. RESULTS: Overall, pain decreased in both arms. However, pain decreased more in the intervention arm as compared to the control arm. The total change in the mean score of the NRS-11 from baseline to follow-up was 3.1 and 6.19 in the control and ST arms, respectively. Differences between pain scores in both arms became significant from day 3 onwards. Mean morphine dose was significantly lower in the intervention arm from day 7 onwards. LIMITATIONS: The study followed the patients until one week after the last treatment session and encouraged patients to return for treatment if their pain returned to previous levels within 10 days. Moreover, patients in the control arm received the standard of care in the form of pharmacological treatment but did not receive either transcutaneous electrical nerve stimulation (TENS) or a sham (placebo) procedure. CONCLUSIONS: The trial showed that ST is an effective treatment for the management of pain due to head and neck and thoracic cancer. On the basis of this study, the use of ST for the management of refractory cancer pain in head and neck and thoracic cancer is recommended.

Treatment of Déjerine-Roussy syndrome pain with scrambler therapy.

Aim: Déjerine-Roussy syndrome or central thalamic pain can be devastating, and treatment with drugs and even deep brain stimulation can be unsatisfactory. Scrambler therapy is a form of neuromodulation that uses external skin electrodes to send a 'non-pain' signal to the brain, with some success in difficult-to-treat syndromes such as neuromyelitis optica spectrum disorder. We used scrambler therapy to treat a patient with 6 years of disabling Déjerine-Roussy syndrome pain. Methods: A 56-year-old man received multiple daily then monthly treatments with electrode pairs placed just above the area of distal pain. Each treatment was for 40 min. Results: His allodynia and hyperalgesia resolved within 10 min, and his pain score fell to almost zero after 30 min. Months later, he resumed normal activity and is off all his pain medications. No side effects were noted. Conclusion: Scrambler therapy appeared to reverse 6 years of disabling pain safely and economically, and continues to be effective. Further multi-institutional trials are warranted for this rare syndrome.

A Pilot Randomized Sham-Controlled Trial of MC5-A Scrambler Therapy in the Treatment of Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) affects 30% to 40% of patients with cancer with long-lasting disability. Scrambler therapy (ST) appeared to benefit patients in uncontrolled trials, so we performed a randomized sham-controlled Phase II trial of ST. METHODS: The primary end point was "average pain" after 28 days on the Numeric Rating Scale. Each received ten 30-minute sessions of ST on the dermatomes above the painful areas, or sham treatment on the back, typically at L3-5 where the nerve roots would enter the spinal cord. Outcomes included the Brief Pain Inventory (BPI)-CIPN and the EORTC CIPN-20 scale. Patients were evaluated before treatment (day 0), day 10, and days 28, 60, and 90. RESULTS: Data regarding pain as a primary outcome were collected for 33 of the 35 patients. There were no significant differences between the sham and the "real" ST group at day 10, 28, 60, or 90, for average pain, the BPI, or EORTC CIPN-20. Individual responses were noted during the ST treatment on the real arm, but most dissipated by day 30. There was improvement in the sensory subscale of the CIPN-20 at 2 months in the "real" group (P = .14). All "real" patients wanted to continue treatment if available. DISCUSSION: We observed no difference between sham and real ST CIPN treatment. Potential reasons include at least the following: ST does not work; the sham treatment had some effect; small sample size with heterogeneous patients; misplaced electrodes on an area of nonpainful but damaged nerves; or a combination of these factors.

Successful Treatment of Scar Pain with Scrambler Therapy.

Scar pain from thoracotomy, hepatectomy, or similar operations is distressing and difficult to treat. Scrambler Therapy is a novel form of superficial neuromodulation that has been effective in treating different types of neuropathic pain. We report here two cases of dramatic relief from disabling scar pain with one or two sessions of Scrambler Therapy.

Case Report: Scrambler Therapy for Treatment-Resistant Central Neuropathic Pain in a Patient with Transverse Myelitis.

Central neuropathic pain is a severely disabling consequence of conditions that cause tissue damage in the central nervous system. It is often refractory to treatments commonly used for peripheral neuropathy. Scrambler therapy is an emerging noninvasive pain-modifying technique that uses transcutaneous electrical stimulation of nociceptive fibers with the intent of reorganizing maladaptive signaling pathways. It has been examined for the treatment of peripheral neuropathy with favorable safety and efficacy outcomes, but its application to central neuropathic pain has not been reported in transverse myelitis. We describe the use of Scrambler therapy in a patient with persistent central neuropathic pain due to transverse myelitis. The patient had tried multiple drugs for treatment of the pain, but they were not effective or caused adverse effects. After a course of Scrambler therapy, pain scores improved considerably more than what was reported with previous pharmacologic and nonpharmacologic interventions. This case supports further investigation of Scrambler therapy in multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated disorders that damage the central nervous system.

Inside the Scrambler Therapy, a Noninvasive Treatment of Chronic Neuropathic and Cancer Pain: From the Gate Control Theory to the Active Principle of Information.

Scrambler therapy (ST) is an electro-analgesia therapy for the noninvasive treatment of chronic neuropathic and cancer pain based on a new generation of medical device that uses 5 artificial neurons and is based on a novel theoretical model the differs from gate control theory. The active principle with Scrambler Therapy is such that synthetic "non-pain" information is transmitted by C fiber surface receptors. This is a different theoretical mechanism than the traditional electric stimulation of A-Beta fibers to produce paresthesia and/or block the conduction of nerve fibers to produce an analgesic effect, that is, via TENS (transcutaneous electrical nerve stimulation) machines. Scrambler therapy was developed to treat chronic neuropathic pain and cancer pain resistant to opioids and other types of treatments. The goal of Scrambler Therapy is to eliminate pain during treatment and allow for long-lasting analgesia after a series of 10 to 12 consecutive treatments performed over a 2-week period. The aim of this review is to clarify the underlying theory of Scrambler Therapy and describe the appropriate usage method that maximizes its effectiveness while reducing bias and deepen the explanation of the artificial neuron technology associated with Scrambler Therapy.