Scrambler Therapy for Diabetic Neuropathy Treatment

Diabetic neuropathy (DN) is a frequent complication of diabetes that presents significant treatment challenges (Marineo et al., 2012). Traditional treatments often offer limited pain relief, and while spinal cord stimulation can be effective, it is an invasive and costly intervention (Marineo et al., 2012). Scrambler Therapy has emerged as a noninvasive neuromodulation technique that shows promise in alleviating diabetic neuropathy (Marineo et al., 2012).

What is Scrambler Therapy?
Scrambler Therapy is a cutaneous electrostimulation method approved by the FDA for neuromodulation of pain (Lee et al., 2019). It is applied to manage various chronic neuropathic pain conditions, including cancer and non-cancer pain, as well as numbness and tingling (Smith et al., 2023).

Key features of Scrambler Therapy include:
It uses a device with paired electrical stimulation channels to deliver synthetic “non-pain” or “normal-self” electrical signals, which replace the body’s pain information (Marineo et al., 2012).
These signals are hypothesized to travel through peripheral afferent somatosensory C fibers to the brain, targeting the region of pain (Marineo et al., 2012).
The treatment is non-invasive, involving the placement of electrodes on the skin (Smith et al., 2023).

How Does Scrambler Therapy Work?
Although the precise mechanisms are not fully understood, Scrambler Therapy is believed to “scramble” afferent pain signals and substitute them with synthetic “non-pain” information via cutaneous nerves (Marineo et al., 2012).

Key aspects of its mechanism include:

• Non-pain information delivery: Scrambler Therapy provides new “nonpain” information, and patients report new sensations in the pain area (Marineo et al., 2012).
• Not simple C-fiber stimulation: Per Marineo et al. (2012), Scrambler Therapy is not a simple C-fiber electrical stimulation, which would produce pain (Marineo et al., 2012).
• Not producing paresthesias: Scrambler Therapy does not cause numbness, and the patient can still feel other noxious stimuli (Marineo et al., 2012).
• Fast analgesia: Scrambler Therapy analgesia occurs quickly, suggesting receptors transmit “nonpain” information (Marineo et al., 2012).
• Sustained pain relief: Sustained pain relief suggests a resetting of calcium channels or remodulation of the pain system’s response (Marineo et al., 2012).
• Dermatomal sensation: Patients feel the sensation throughout the dermatome, suggesting the spread of “nonpain” information along nerve transmission lines (Marineo et al., 2012).
• Each set of electrodes acts as an artificial neuron, capturing the surface receptors of the C-fibres and replacing the pain signal with a “non-pain signal” (Marineo et al., 2012). This may reset central sensitization (Marineo et al., 2012). Scrambler Therapy also redirects cerebral blood flow from the pain centers to the frontal inhibitory centers and restores the serum balance of pain-activating and inhibitory mRNAs and their proteins (Lee et al., 2019).

Application of Scrambler Therapy

The application of Scrambler Therapy involves specific techniques to maximize its effectiveness.

• Electrode Placement: Electrodes are positioned in areas without pain, attached to normal sensory areas around the ankle. The electrodes are placed in the pathway of nerves that innervate the areas of pain, tingling, and/or numbness, but not directly on the symptomatic areas of skin (Lee et al., 2019).
• Treatment Parameters: Each treatment session typically lasts 45 minutes and is administered once a week for 10 weeks (Marineo et al., 2012). During the session, an electrical stimulus is applied, with the intensity gradually increased to the maximum value tolerated by the patient (Lee et al., 2019).
• Stimulus Adjustment: The stimulus is increased to the maximum intensity individually bearable by the patient without causing additional pain or discomfort (Lee et al., 2019). The operator can add or move channels to increase coverage, utilizing up to five channels or paired sets of electrodes (Lee et al., 2019). If pain is not relieved, the electrode placement or stimulus is changed (Lee et al., 2019).

Evidence for Scrambler Therapy in Diabetic Neuropathy

A case report describes the successful use of Scrambler Therapy to treat a patient with diabetic peripheral neuropathy, where typical neuropathic pain medications had failed (Marineo et al., 2012). The patient’s NRS score decreased from 6/10 to 3/10 after the first Scrambler Therapy session, and after 10 sessions, the patient reported an NRS score of 2/10 for bilateral plantar foot pain (Marineo et al., 2012).
Another case report of a 70-year-old male with diabetic small fiber neuropathy (DSFN) showed that after 5 consecutive daily treatments, each lasting 40 minutes, his pain improved to 0 out of 10 in all regions, and his balance improved (Smith et al., 2023).
Scrambler Therapy has demonstrated success in randomized controlled trials for conditions such as low-back pain, spinal cord stenosis, postherpetic neuropathy, chemotherapy-induced neuropathy, and neuromyelitis optica spectrum disorder (Marineo et al., 2012).

Comparison with Other Treatments

• Conventional treatments: While conventional treatments such as antidepressants, anticonvulsants, and opiate analgesics are available, they often come with significant side effects, limited efficacy, and financial burden (Smith et al., 2023).
• TENS: Scrambler Therapy is distinct from TENS (Marineo et al., 2012). Scrambler Therapy is based on the theory that an electrical stimulus on the skin can activate particular sodium–calcium channels to produce action potentials and sensations perceived as non-noxious and innocuous instead of painful (Marineo et al., 2012).

Spinal cord stimulation (SCS): SCS is an effective but invasive and expensive option (Marineo et al., 2012). Scrambler Therapy is less invasive than SCS therapy (Marineo et al., 2012).

References

Marineo, G., Iorno, V., Gandini, C., Moschini, V., & Smith, T. J. (2012). Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: Results of a pilot, randomized, controlled trial. Journal of Pain and Symptom Management, 43(1), 87–95.

Lee, Y. S., Park, M. K., Park, H. S., & Kim, W. J. (2019). Scrambler therapy for the treatment of diabetic peripheral neuropathy pain: A case report. Medicine, 98(20), e15695.

Smith, T. J., Wang, E. J., & Loprinzi, C. L. (2023). Cutaneous electroanalgesia for relief of chronic and neuropathic pain. New England Journal of Medicine, 389(2), 158-164.