Refractory Chronic Neuropathic Pain Successfully Treated With Scrambler Therapy

Neuropathic pain is a prevalent and debilitating condition that affects roughly 7% of the world’s population and is expected to increase in coming years.¹ Of the 7% of individuals with neuropathic pain, 20%–30% may develop chronic pain and be refractory to pain medications.² Neuropathic pain can be from central or peripheral causes and is difficult to treat, often requiring a multimodal treatment regimen, as less than 50% of patients with neuropathic pain get relief with monotherapies.³ First-line therapies for neuropathic pain include serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and gabapentinoids.⁴ Nonpharmacologic management of neuropathic pain includes conservative therapies such as acupuncture, exercise, light therapies, and electric therapies.⁵

Recently, newer treatments have emerged as potential therapeutics for neuropathic pain. Scrambler therapy is a noninvasive electrical cutaneous stimulation modality that aims to realign maladaptive pain pathways.⁶ Scrambler therapy has shown some promise in cancer-related neuropathic pain⁷ and chronic neuropathic pain.^8,9 When compared to existing cutaneous neuromodulatory modalities such as transcutaneous electrical stimulation (TENS), there are a number of differences. For instance, TENS targets the A-fibers with low-intensity signals to inhibit dorsal horn interneurons and to decrease pain acutely and possibly some C-fibers.¹⁰ Scrambler therapy targets the C-fibers with a constantly randomizing magnitude of a sinusoidal (or half-sinusoidal) waveform intended to decrease central sensitization of nociception; however, the exact mechanism remains unclear.¹⁰ When compared to TENS, scrambler therapy has shown greater improvements in patients with chemotherapy-induced neuropathy for impression of change and quality of life.¹¹ However, for medication-refractive chronic neuropathic pain, scrambler therapy’s role remains largely unknown.

Case Report

A 63-year-old woman with a medical history significant for eosinophilic esophagitis and remote Guillain-Barre with no residual symptoms presented with a 6-month history of bilateral upper and lower extremity burning with associated electrical shooting pain. In her upper extremities, the pain started from her elbows and radiated down to her arms. In her lower extremities, the pain started in the mid-calf and radiated to her toes, and the pain was worse on the plantar surface of her foot bilaterally. The patient rated the pain as 6/10 in her arms and 9/10 in her feet.

She was extensively evaluated by the neurology department; however, workup thus far was negative. The current working diagnosis from neurology was small fiber neuropathy; however, the biopsy was negative. The patient had some relief with gabapentin, pregabalin, and prednisone; however, she endorsed cognitive side effects from these medications. Other medications including duloxetine, nortriptyline, and oxcarbazepine caused significant cognitive side effects such as confusion and sedation. On physical examination, the patient did not demonstrate signs of complex regional pain syndrome such as allodynia, hyperalgesia, temperature changes, or sweating; however, she did have swelling of her right arm and right foot. Due to the presence of sudomotor changes, factitious disorder and functional neurological deficit were not considered on the differential diagnosis despite negative biopsy.

After lengthy discussion and deliberation with the patient, scrambler therapy was recommended to help manage her symptoms. After some initial reluctance, the patient agreed to trial the therapy. Following her initial treatment, the patient reported significant pain relief with this intervention, rating her pain between 0 and 3 out of 10 in severity. Additionally, she was able to perform activities of daily living and had improved sleep because of her pain relief. The patient was closely followed for any adverse events, but none were identified in her case.

Discussion

Scrambler therapy is a neuromodulation technique that is a viable treatment modality for patients with chronic neuropathic pain. By delivering electrical signals to specific dermatomes, its goal is to flood C-fibers with nonpain signals, thereby blocking pain transmission signals from traveling to the brain and resetting abnormal pain processing. Additionally, scrambler therapy is well tolerated and has minimal side effects, making it a viable treatment option for patients with refractory neuropathic pain. Our patient was suffering from chronic neuropathic pain that was refractory to both first-line and second-line pharmacologic agents.

Moreover, the patient did not have a clear diagnosis, as her biopsy was negative for evidence of small fiber neuropathy, making it difficult to resolve the underlying medical issue. However, due to scrambler therapy being identified as having a higher impression of change in prior clinical studies¹¹ compared to other transcutaneous modalities, there is the potential for patients with functional neurological disorder to feel psychosomatic symptom improvement with the treatment as well. The patient responded well to scrambler therapy and has been thriving both at home and at work. This case highlights the promising potential for scrambler therapy in the treatment of chronic neuropathic pain. More clinical trials are necessary to establish defined clinical protocols, long-term efficacy, and specific settings for optimal electrical delivery.

Conclusion

Scrambler therapy is an innovative treatment option for patients with chronic neuropathic pain, especially for patients who did not respond to conventional interventions. Considering its noninvasive nature and minimal side effects, scrambler therapy can play a role in a multimodal approach to pain management. More studies are needed to investigate its mechanism of action and long-term benefit.

Article Information

Published Online: May 26, 2026. https://doi.org/10.4088/PCC.25cr04084
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(3):25cr04084
Submitted: September 14, 2025; accepted January 26, 2026.
To Cite: Sadik E, Goodwin BJ, Jain A, et al Refractory chronic neuropathic pain successfully treated with scrambler therapy. Prim Care Companion CNS Disord 2026;28(3):25cr04084.
Author Affiliations: Department of Physical Medicine and Rehabilitation, Johns Hopkins University, Baltimore, Maryland (Sadik, Goodwin, Jain, Friedlander); Futures Forward Research Institute, Toms River, New Jersey (Goodwin); Rowan-Virtua School of Osteopathic Medicine, Stratford, New Jersey (Mitchell); St. George’s University School of Medicine, True Blue, Grenada (Alahdadi).
Corresponding Author: Brandon J. Goodwin, DO, Department of Physical Medicine and Rehabilitation, Johns Hopkins University, 600 North Wolfe Street, Phipps 174, Baltimore, MD 21287 ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect patient anonymity.
ORCID: Eliot Sadik: https://orcid.org/0000-0002-4146-4042; Brandon J. Goodwin: https://orcid.org/0000-0002-3965-4664; Ankur Jain: https://orcid.org/0009-0000-4925-9310; Jessica Mitchell: https://orcid.org/0009-0005-5312-5485; Tracy Friedlander: https://orcid.org/0000-0003-3017-1444