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Clinical Studies Published (Update October 15, 2023)

The research was carried out in the databases from PubMed/Medline.

Note: the proper use of Scrambler Therapy, being operator-dependent, allows only for a partial double-blind or single-blind trial design. Attempts to do a complete double-blind clinical trial automatically cause substantial changes in the standard treatment protocol, which requires substantial patient interaction to determine proper placements of electrodes and intensity of treatment. These changes prevent the operator to follow the normal procedures registered in the healthcare authorizations and can erase or significantly reduce the efficacy of the treatment, consequently invalidating the scientific data.

Scientific articles of reference (theory, methodology, clinic)

Marineo G. Inside the Scrambler Therapy, a Noninvasive Treatment of Chronic Neuropathic and Cancer Pain: From the Gate Control Theory to the Active Principle of Information. Integr Cancer Ther. 2019 Jan-Dec;18:1534735419845143. doi: 10.1177/1534735419845143. PMID: 31014125; PMCID: PMC6482660. Marineo G.

Untreatable pain resulting from abdominal cancer: new hope from biophysics? JOP. 2003 Jan;4(1):1-10. PMID: 12555009.

Review

Smith TJ, Wang EJ, Loprinzi CL. Cutaneous Electroanalgesia for Relief of Chronic and Neuropathic Pain. N Engl J Med. 2023 Jul 13;389(2):158-164. doi: 10.1056/NEJMra2110098. PMID: 37437145.

Wang EJ, Limerick G, D'Souza RS, Lobner K, Williams KA, Cohen SP, Smith TJ. Safety of Scrambler Therapy: A Systematic Review of Complications and Adverse Effects. Pain Med. 2023 Mar 1;24(3):325-340. doi: 10.1093/pm/pnac137. PMID: 36069623.

Karri J, Marathe A, Smith TJ, Wang EJ. The Use of Scrambler Therapy in Treating Chronic Pain Syndromes: A Systematic Review. Neuromodulation. 2022 Jun 9:S1094-7159(22)00681-X. doi: 10.1016/j.neurom.2022.04.045. Epub ahead of print. PMID: 35691908.

Wang EJ, Limerick G, D'Souza RS, Lobner K, Williams KA, Cohen SP, Smith TJ. Safety of Scrambler Therapy: A Systematic Review of Complications and Adverse Effects. Pain Med. 2022 Sep 7:pnac137. doi: 10.1093/pm/pnac137. Epub ahead of print. PMID: 36069623.

Nair A. Scrambler therapy: An opioid-sparing, non-invasive modality for chronic pain in patients. Saudi J Anaesth. 2022 Oct-Dec;16(4):525-526. doi: 10.4103/sja.sja_366_22. Epub 2022 Sep 3. PMID: 36337412; PMCID: PMC9630698.

Wang EJ, Berninger LE, Komargodski O, Smith TJ. Painful Diabetic Neuropathy - Spinal Cord Stimulation, Peripheral Nerve Stimulation, Transcutaneous Electrical Nerve Stimulation, and Scrambler Therapy: A Narrative Review. Pain Physician. 2022 Nov;25(8):E1163-E1173. PMID: 36375183.

Abdi S, Chung M, Marineo G. Scrambler therapy for noncancer neuropathic pain: a focused review. Curr Opin Anaesthesiol. 2021 Dec 1;34(6):768-773. doi: 10.1097/ACO.0000000000001073. PMID: 34653073

Majithia N, Smith TJ, Coyne PJ, Abdi S, Pachman DR, Lachance D, Shelerud R, Cheville A, Basford JR, Farley D, O'Neill C, Ruddy KJ, Sparadeo F, Beutler A, Loprinzi CL. Scrambler Therapy for the management of chronic pain. Support Care Cancer. 2016 Jun;24(6):2807-14. doi: 10.1007/s00520-016-3177-3. Epub 2016 Apr 4. PMID: 27041741; PMCID: PMC4973603.

Randomized Controlled Trial 

Kashyap K, Singh V, Dwivedi SN, Gielen J, Bhatnagar S. Scrambler Therapy Enhances Quality of Life in Cancer Patients in a Palliative Care Setting: A Randomised Controlled Trial. Indian J Palliat Care. 2022 Jul-Sep;28(3):287-294. doi: 10.25259/IJPC_94_2021. Epub 2022 Jul 13. PMID: 36072252; PMCID: PMC9443118.

Lee SY, Park CH, Cho YS, Kim L, Yoo JW, Joo SY, Seo CH. Scrambler Therapy for Chronic Pain after Burns and Its Effect on the Cerebral Pain Network: A Prospective, Double-Blinded, Randomized Controlled Trial. J Clin Med. 2022 Jul 22;11(15):4255. doi: 10.3390/jcm11154255. PMID: 35893347; PMCID: PMC9332864.

Note: the proper use of Scrambler Therapy, being operator-dependent, allows only for a partial double-blind or single-blind trial design.

Childs DS, Le-Rademacher JG, McMurray R, Bendel M, O'Neill C, Smith TJ, Loprinzi CL. Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis. J Pain Symptom Manage. 2021 Jun;61(6):1247-1253. doi: 10.1016/j.jpainsymman.2020.11.025. Epub 2020 Nov 27. PMID: 33249081.

Kashyap K, Singh V, Mishra S, Dwivedi SN, Bhatnagar S. The Efficacy of Scrambler Therapy for the Management of Head, Neck and Thoracic Cancer Pain: A Randomized Controlled Trial. Pain Physician. 2020 Sep;23(5):495-506. PMID: 32967392.

Mealy MA, Kozachik SL, Cook LJ, Totonis L, Salazar RA, Allen JK, Nolan MT, Smith TJ, Levy M. Scrambler therapy improves pain in neuromyelitis optica: A randomized controlled trial. Neurology. 2020 May 5;94(18):e1900-e1907. doi: 10.1212/WNL.0000000000009370. Epub 2020 Apr 8. PMID: 32269109; PMCID: PMC7274926.

Loprinzi C, Le-Rademacher JG, Majithia N, McMurray RP, O'Neill CR, Bendel MA, Beutler A, Lachance DH, Cheville A, Strick DM, Black DF, Tilburt JC, Smith TJ. Scrambler therapy for chemotherapy neuropathy: a randomized phase II pilot trial. Support Care Cancer. 2020 Mar;28(3):1183-1197. doi: 10.1007/s00520-019-04881-3. Epub 2019 Jun 17. PMID: 31209630.

Marineo G, Iorno V, Gandini C, Moschini V, Smith TJ. Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot, randomized, controlled trial. J Pain Symptom Manage. 2012 Jan;43(1):87-95. doi: 10.1016/j.jpainsymman.2011.03.015. Epub 2011 Jul 16. PMID: 21763099.

Clinical Trial

Tomasello C, Pinto RM, Mennini C, Conicella E, Stoppa F, Raucci U. Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study. Pediatr Blood Cancer. 2018 Jul;65(7):e27064. doi: 10.1002/pbc.27064. Epub 2018 Apr 6. PMID: 29630779.

Coyne PJ, Wan W, Dodson P, Swainey C, Smith TJ. A trial of Scrambler therapy in the treatment of cancer pain syndromes and chronic chemotherapy-induced peripheral neuropathy. J Pain Palliat Care Pharmacother. 2013 Dec;27(4):359-64. doi: 10.3109/15360288.2013.847519. Epub 2013 Oct 21. PMID: 24143893; PMCID: PMC4378693.

Kashyap K, Joshi S, Vig S, Singh V, Bhatnagar S. Impact of Scrambler Therapy on Pain Management and Quality of Life in Cancer Patients: A Study of Twenty Cases. Indian J Palliat Care. 2017 Jan-Mar;23(1):18-23. doi: 10.4103/0973-1075.197948. Erratum in: Indian J Palliat Care. 2017 Apr-Jun;23 (2):217. PMID: 28216858; PMCID: PMC5294432.

Lee SC, Park KS, Moon JY, Kim EJ, Kim YC, Seo H, Sung JK, Lee DJ. An exploratory study on the effectiveness of "Calmare therapy" in patients with cancer-related neuropathic pain: A pilot study. Eur J Oncol Nurs. 2016 Apr;21:1-7. doi: 10.1016/j.ejon.2015.12.001. Epub 2015 Dec 29. PMID: 26952672.

Observational - Prospective  Study

Ricci M, Fabbri L, Pirotti S, Ruffilli N, Foca F, Maltoni M. Scrambler therapy: what's new after 15 years? The results from 219 patients treated for chronic pain. Medicine (Baltimore). 2019 Jan;98(2):e13895. doi: 10.1097/MD.0000000000013895. PMID: 30633163; PMCID: PMC6336541.

Pachman DR, Weisbrod BL, Seisler DK, Barton DL, Fee-Schroeder KC, Smith TJ, Lachance DH, Liu H, Shelerud RA, Cheville AL, Loprinzi CL. Pilot evaluation of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2015 Apr;23(4):943-51. doi: 10.1007/s00520-014-2424-8. Epub 2014 Sep 24. PMID: 25245776; PMCID: PMC4383262.

Compagnone C, Tagliaferri F; Scrambler Therapy Group. Chronic pain treatment and scrambler therapy: a multicenter retrospective analysis. Acta Biomed. 2015 Sep 14;86(2):149-56. PMID: 26422429.Acta Biomed

Notaro P, Dell'Agnola CA, Dell'Agnola AJ, Amatu A, Bencardino KB, Siena S. Pilot evaluation of scrambler therapy for pain induced by bone and visceral metastases and refractory to standard therapies. Support Care Cancer. 2016 Apr;24(4):1649-54. doi: 10.1007/s00520-015-2952-x. Epub 2015 Sep 26. PMID: 26408323.

Smith TJ, Marineo G. Treatment of Postherpetic Pain With Scrambler Therapy, a Patient-Specific Neurocutaneous Electrical Stimulation Device. Am J Hosp Palliat Care. 2018 May;35(5):812-813. doi: 10.1177/1049909113494002. Epub 2013 Jul 8. PMID: 23838448.

Ko YK, Lee HY, Lee WY. Clinical experiences on the effect of scrambler therapy for patients with postherpetic neuralgia. Korean J Pain. 2013 Jan;26(1):98-101. doi: 10.3344/kjp.2013.26.1.98. Epub 2013 Jan 4. PMID: 23342218; PMCID: PMC3546221.

Ghatak RK, Nandi SN, Bhakta A, Mandal GC, Bandyopadhyay M, Kumar S. Prospective study of application of biological communication (cybernatics) in management of chronic low back pain--a preliminary report. Nepal Med Coll J. 2011 Dec;13(4):257-60. PMID: 23016475.

Sabato AF, Marineo G, Gatti A. Scrambler therapy. Minerva Anestesiol. 2005 Jul-Aug;71(7-8):479-82. PMID: 16012423.

Case Reports

Wang AT, Wang EJ, Smith TJ, Razzak R, Christo PJ. Scrambler Therapy for Patients With Complex Regional Pain Syndrome: A Case Series. J Palliat Med. 2023 Sep;26(9):1302-1306. doi: 10.1089/jpm.2022.0539. Epub 2023 Jul 21. PMID: 37477679

Murphy T, Erdek M, Smith TJ. Scrambler Therapy for the Treatment of Pain in Schwannomatosis. Cureus. 2022 Mar 13;14(3):e23124. doi: 10.7759/cureus.23124. PMID: 35464572; PMCID: PMC9001870.

Wang EJ, Berninger LE, Pantelyat AY, Hunsberger JB, Smith TJ. Scrambler Therapy for the Treatment of Multiple System Atrophy-Parkinsonian Subtype Pain: A Case Report. A A Pract. 2022 Jan 18;16(1):e01560. doi: 10.1213/XAA.0000000000001560. PMID: 35050906.

Murphy TK, Pardo CA, Roda RH, Stone RL, Smith TJ. Successful Treatment of Paraneoplastic Neuropathy and Pruritis With Scrambler Therapy: A Case Report. Cureus. 2022 Jul 14;14(7):e26861. doi: 10.7759/cureus.26861. PMID: 35978756; PMCID: PMC9375651.

Christo PJ, Kamson DO, Smith TJ. Treatment of Déjerine-Roussy syndrome pain with scrambler therapy. Pain Manag. 2020 May;10(3):141-145. doi: 10.2217/pmt-2019-0065. Epub 2020 May 12. PMID: 32394815.Pain Manag

Ahuja D, Bharati SJ, Gupta N, Kumar V, Bhatnagar S. Scrambler therapy: A ray of hope for refractory chemotherapy-induced peripheral neuropathy. Indian J Cancer. 2020 Jan-Mar;57(1):93-97. doi: 10.4103/ijc.IJC_361_18. PMID: 32129300.

Yarchoan M, Naidoo J, Smith TJ. Successful Treatment of Scar Pain with Scrambler Therapy. Cureus. 2019 Oct 14;11(10):e5903. doi: 10.7759/cureus.5903. PMID: 31777690; PMCID: PMC6853271.

Mealy MA, Newsome SD, Kozachik SL, Levy M, Smith TJ. Case Report: Scrambler Therapy for Treatment-Resistant Central Neuropathic Pain in a Patient with Transverse Myelitis. Int J MS Care. 2019 Mar-Apr;21(2):76-80. doi: 10.7224/1537-2073.2017-083. PMID: 31049038; PMCID: PMC6489430.

Fabbri L, Pirotti SP, Rosati M, Ruffilli N, Maltoni M, Ricci M. Phantom limb pain successfully treated with scrambler therapy. Minerva Anestesiol. 2018 May;84(5):642-643. doi: 10.23736/S0375-9393.18.12490-4. Epub 2018 Jan 17. PMID: 29343050.

D'Amato SJ, Mealy MA, Erdek MA, Kozachik S, Smith TJ. Scrambler Therapy for the Treatment of Chronic Central Pain: A Case Report. A A Pract. 2018 Jun 15;10(12):313-315. doi: 10.1213/XAA.0000000000000695. PMID: 29293482.

Smith T, Cheville AL, Loprinzi CL, Longo-Schoberlein D. Scrambler Therapy for the Treatment of Chronic Post-Mastectomy Pain (cPMP). Cureus. 2017 Jun 21;9(6):e1378. doi: 10.7759/cureus.1378. PMID: 28775918; PMCID: PMC5522013.

Raucci U, Tomasello C, Marri M, Salzano M, Gasparini A, Conicella E. Scrambler Therapy(®) MC-5A for Complex Regional Pain Syndrome: Case Reports. Pain Pract. 2016 Sep;16(7):E103-9. doi: 10.1111/papr.12474. Epub 2016 Jul 2. PMID: 27370908.

Smith TJ, Auwaerter P, Knowlton A, Saylor D, McArthur J. Treatment of human immunodeficiency virus-related peripheral neuropathy with Scrambler Therapy: a case report. Int J STD AIDS. 2017 Feb;28(2):202-204. doi: 10.1177/0956462416656688. Epub 2016 Jul 10. PMID: 27330020.

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