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.

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.

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.

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.
OBJECTIVE: This meta-analysis aimed to investigate the efficacy of ST for the management of chronic pain.
METHODS: 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.
CONCLUSIONS: 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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).
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).
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.
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.

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.

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.

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.

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.