Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 68% of patients who receive neurotoxic chemotherapy and lasts at least 6 months post-chemotherapy in approximately 30% of individuals. CIPN is associated with decreased quality of life and functional impairments. Evidence suggests that CIPN symptoms are caused, in part, by enhanced excitability and impaired inhibition in the central nervous system. Transcutaneous electrical nerve stimulation (TENS) decreases pain by counteracting both of these mechanisms and is efficacious in other conditions associated with neuropathic pain. This single-arm study (n = 29) assessed the feasibility of investigating TENS for CIPN after chemotherapy completion using a wireless, home-based TENS device. Eighty-one percent of eligible patients who were approached enrolled, and 85% of participants who received the TENS device completed the primary (6-week) study term. Qualitative interview data suggest that use of the device on the continuous setting that automatically alternates between 1-h stimulation and rest periods for 5 h/day would be acceptable to most participants. Significant (i.e., p < 0.05) improvements were observed with the EORTC-CIPN20 (percent change from baseline: 13%), SF-MPQ-2 (52%), numeric rating scale of pain (38%), tingling (30%), numbness (20%), and cramping (53%), and UENS large fiber sensation subscore (48%). Preliminary data that support the reliability and construct validity of the UENS for CIPN in cancer survivors are also provided. Together these data suggest that it is feasible to evaluate TENS for CIPN using a wireless, home-based device and that further evaluation of TENS for CIPN in a randomized clinical trial is warranted.
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Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 155(12):2461–2470. https://doi.org/10.1016/j.pain.2014.09.020
NCI Sureillance, Epidemiology, and End Results Program https://seer.cancer.gov/statfacts/
Kneis S, Wehrle A, Freyler K, Lehmann K, Rudolphi B, Hildenbrand B, Bartsch HH, Bertz H, Gollhofer A, Ritzmann R (2016) Balance impairments and neuromuscular changes in breast cancer patients with chemotherapy-induced peripheral neuropathy. Clin Neurophysiol 127(2):1481–1490. https://doi.org/10.1016/j.clinph.2015.07.022
Gewandter JS, Fan L, Magnuson A, Mustian K, Peppone L, Heckler C, Hopkins J, Tejani M, Morrow GR, Mohile SG (2013) Falls and functional impairments in cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study. Support Care Cancer 21(7):2059–2066. https://doi.org/10.1007/s00520-013-1766-y
Kolb NA, Smith AG, Singleton JR, Beck SL, Stoddard GJ, Brown S, Mooney K (2016) The Association of Chemotherapy-Induced Peripheral Neuropathy Symptoms and the risk of falling. JAMA neurol 73(7):860–866. https://doi.org/10.1001/jamaneurol.2016.0383
Bao T, Basal C, Seluzicki C, Li SQ, Seidman AD, Mao JJ (2016) Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk. Breast Cancer Res Treat 159(2):327–333. https://doi.org/10.1007/s10549-016-3939-0
Tofthagen C (2010) Patient perceptions associated with chemotherapy-induced peripheral neuropathy. Clin J Oncol Nurs 14(3):E22–E28. https://doi.org/10.1188/10.CJON.E22-E28
Hong JS, Tian J, Wu LH (2014) The influence of chemotherapy-induced neurotoxicity on psychological distress and sleep disturbance in cancer patients. Curr Oncol 21(4):174–180. https://doi.org/10.3747/co.21.1984
Mols F, Beijers T, Vreugdenhil G, van de Poll-Franse L (2014) Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer 22 (8):2261–2269. doi:https://doi.org/10.1007/s00520-014-2255-7
Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, Bressler LR, Fadul CE, Knox C, Le-Lindqwister N, Gilman PB, Shapiro CL (2013) Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA 309(13):1359–1367. https://doi.org/10.1001/jama.2013.2813
Cata JP, Weng HR, Chen JH, Dougherty PM (2006) Altered discharges of spinal wide dynamic range neurons and down-regulation of glutamate transporter expression in rats with paclitaxel-induced hyperalgesia. Neuroscience 138(1):329–338. https://doi.org/10.1016/j.neuroscience.2005.11.009
Cata JP, Weng HR, Dougherty PM (2008) Behavioral and electrophysiological studies in rats with cisplatin-induced chemoneuropathy. Brain Res 1230:91–98. https://doi.org/10.1016/j.brainres.2008.07.022
Weng HR, Cordella JV, Dougherty PM (2003) Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. Pain 103(1–2):131–138
Nahman-Averbuch H, Yarnitsky D, Granovsky Y, Sprecher E, Steiner M, Tzuk-Shina T, Pud D (2011) Pronociceptive pain modulation in patients with painful chemotherapy-induced polyneuropathy. JPSM 42(2):229–238. https://doi.org/10.1016/j.jpainsymman.2010.10.268
Ossipov MH, Dussor GO, Porreca F (2010) Central modulation of pain. J Clin Invest 120(11):3779–3787. https://doi.org/10.1172/Jci43766
Kwon M, Altin M, Duenas H, Alev L (2014) The role of descending inhibitory pathways on chronic pain modulation and clinical implications. Pain Practice 14(7):656–667. https://doi.org/10.1111/papr.12145
Staud R (2012) Abnormal endogenous pain modulation is a shared characteristic of many chronic pain conditions. Expert Rev Neurother 12(5):577–585. https://doi.org/10.1586/ern.12.41
Sluka K, Walsh D (2016) Transcutaneous electrical nerve stimulation and interferential therapy. In: Mechanisms and management of pain for the physical therapist. Lippincott Williams & Wilkins
Ma YT, Sluka KA (2001) Reduction in inflammation-induced sensitization of dorsal horn neurons by transcutaneous electrical nerve stimulation in anesthetized rats. Exp Brain Res 137(1):94–102
Sluka KA, Vance CG, Lisi TL (2005) High-frequency, but not low-frequency, transcutaneous electrical nerve stimulation reduces aspartate and glutamate release in the spinal cord dorsal horn. J Neurochem 95(6):1794–1801. https://doi.org/10.1111/j.1471-4159.2005.03511.x
DeSantana JM, da Silva LF, Sluka KA (2010) Cholecystokinin receptors mediate tolerance to the analgesic effect of TENS in arthritic rats. Pain 148(1):84–93. https://doi.org/10.1016/j.pain.2009.10.011
Sluka KA, Deacon M, Stibal A, Strissel S, Terpstra A (1999) Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats. J Pharmacol Exp Ther 289(2):840–846
Leonard G, Goffaux P, Marchand S (2010) Deciphering the role of endogenous opioids in high-frequency TENS using low and high doses of naloxone. Pain 151(1):215–219. https://doi.org/10.1016/j.pain.2010.07.012
Dailey DL, Rakel BA, Vance CG, Liebano RE, Amrit AS, Bush HM, Lee KS, Lee JE, Sluka KA (2013) Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia. Pain 154(11):2554–2562. https://doi.org/10.1016/j.pain.2013.07.043
Kumar D, Alvaro MS, Julka IS, Marshall HJ (1998) Diabetic peripheral neuropathy. Effectiveness of electrotherapy and amitriptyline for symptomatic relief. Diabetes Care 21(8):1322–1325
Kumar D, Marshall HJ (1997) Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation. Diabetes Care 20(11):1702–1705
Carbonario F, Matsutani LA, Yuan SL, Marques AP (2013) Effectiveness of high-frequency transcutaneous electrical nerve stimulation at tender points as adjuvant therapy for patients with fibromyalgia. Eur J Phys Rehabil Med 49(2):197–204
Yarnitsky D, Volokh L, Ironi A, Weller B, Shor M, Shifrin A, Granovsky Y (2017) Nonpainful remote electrical stimulation alleviates episodic migraine pain. Neurology 88(13):1250–1255. https://doi.org/10.1212/WNL.0000000000003760
Postma TJ, Aaronson NK, Heimans JJ, Muller MJ, Hildebrand JG, Delattre JY, Hoang-Xuan K, Lanteri-Minet M, Grant R, Huddart R, Moynihan C, Maher J, Lucey R (2005) The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer 41(8):1135–1139. https://doi.org/10.1016/j.ejca.2005.02.012
Lavoie Smith EM, Barton DL, Qin R, Steen PD, Aaronson NK, Loprinzi CL (2013) Assessing patient-reported peripheral neuropathy: the reliability and validity of the European Organization for Research and Treatment of Cancer QLQ-CIPN20 questionnaire. Qual Life Res 22(10):2787–2799. https://doi.org/10.1007/s11136-013-0379-8
Kieffer JM, Postma TJ, van de Poll-Franse L, Mols F, Heimans JJ, Cavaletti G, Aaronson NK, Group CI-P (2017) Evaluation of the psychometric properties of the EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20). Qual Life Res doi:https://doi.org/10.1007/s11136-017-1626-1, 26, 2999, 3010
Cavaletti G, Jann S, Pace A, Plasmati R, Siciliano G, Briani C, Cocito D, Padua L, Ghiglione E, Manicone M, Giussani G, Italian NG (2006) Multi-center assessment of the Total neuropathy score for chemotherapy-induced peripheral neurotoxicity. JPNS 11(2):135–141. https://doi.org/10.1111/j.1085-9489.2006.00078.x
National Cancer Institute Symptom Management and Health-related Quality of Life Steering Committee Clinical Trial Planning Meeting - Chemotherapy Induced Peripheral Neuropathy: Developing Novel Trials Informed by Translational Science. Executive Summary (2017). https://www.cancer.gov/about-nci/organization/ccct/steering-committees/2015-SxQoLSC-StrategicPriorities. [Accessed 4-12-2018]
Dworkin RH, Turk DC, Revicki DA, Harding G, Coyne KS, Peirce-Sandner S, Bhagwat D, Everton D, Burke LB, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA, Melzack R (2009) Development and initial validation of an expanded and revised version of the short-form McGill pain questionnaire (SF-MPQ-2). Pain 144(1–2):35–42. https://doi.org/10.1016/j.pain.2009.02.007
Singleton JR, Bixby B, Russell JW, Feldman EL, Peltier A, Goldstein J, Howard J, Smith AG (2008) The Utah early neuropathy scale: a sensitive clinical scale for early sensory predominant neuropathy. JPNS 13(3):218–227. https://doi.org/10.1111/j.1529-8027.2008.00180.x
Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM (2001) Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 94(2):149–158
Finn RH (1970) A note on estimating reliability of categorical data. Educ Psychol Meas 30:71–76
Koo TK, Li MY (2016) A guideline of selecting and reporting Intraclass correlation coefficients for reliability research. J Chiropr Med 15(2):155–163. https://doi.org/10.1016/j.jcm.2016.02.012
Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL (2014) Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers. JCO 32:1941–1967. https://doi.org/10.1200/JCO.2013.54.0914
Gibson W, Wand BM, O’Connell NE (2017) Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults. Cochrane Database Syst Rev 9:CD011976. https://doi.org/10.1002/14651858.CD011976.pub2
Wong R, Major P, Sagar S (2016) Phase 2 study of acupuncture-like transcutaneous nerve stimulation for chemotherapy-induced peripheral neuropathy. Integr Cancer Ther 15(2):153–164. https://doi.org/10.1177/1534735415627926
Pachman DR, Weisbrod BL, Seisler DK, Barton DL, Fee-Schroeder KC, Smith TJ, Lachance DH, Liu H, Shelerud RA, Cheville AL, Loprinzi CL (2015) Pilot evaluation of scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy. Support Care Cancer 23(4):943–951. https://doi.org/10.1007/s00520-014-2424-8
Smith TJ, Coyne PJ, Parker GL, Dodson P, Ramakrishnan V (2010) Pilot trial of a patient-specific cutaneous electrostimulation device (MC5-a Calmare (R)) for chemotherapy-induced peripheral neuropathy. JPSM 40(6):883–891. https://doi.org/10.1016/j.jpainsymman.2010.03.022
Argyriou AA, Kyritsis AP, Makatsoris T, Kalofonos HP (2014) Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature. Cancer Manag Res 6:135–147. https://doi.org/10.2147/CMAR.S44261
Noehren B, Dailey DL, Rakel BA, Vance CG, Zimmerman MB, Crofford LJ, Sluka KA (2015) Effect of transcutaneous electrical nerve stimulation on pain, function, and quality of life in fibromyalgia: a double-blind randomized clinical trial. Phys Ther 95(1):129–140. https://doi.org/10.2522/ptj.20140218
We thank the patients for participating in our study. We thank Charles Heckler, PhD, for the assistance with the ICC calculations.
Neurometrix provided the devices and partial financial support for the research assistant’s effort. The Department of Anesthesiology and Perioperative Medicine provided supplemental funds to support the conduct of the trial. The University of Rochester Cancer Center NCI Community Oncology Research Program pilot award provided funds for the equipment to assess neuropathy signs.
Conflicts of interest
Neurometrix provided the devices and electrodes for this investigator-initiated study and funds to support the conduct of the trial. The authors had complete control over the development of the protocol, conduct of the study, and publication of the results. Neurometrix was provided a copy of the manuscript prior to submission for publication, but did not provide any input on the manuscript.
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Gewandter, J.S., Chaudari, J., Ibegbu, C. et al. Wireless transcutaneous electrical nerve stimulation device for chemotherapy-induced peripheral neuropathy: an open-label feasibility study. Support Care Cancer 27, 1765–1774 (2019). https://doi.org/10.1007/s00520-018-4424-6
- Chemotherapy-induced peripheral neuropathy
- Transcutaneous electrical nerve stimulation
- Cancer survivors
- Feasibility trial