|Ahead of print
Looking beyond the obvious: Role of non-invasive electroanalgesia in management of cancer pain
Ridhi Verma, Manu Shivadeva, Divya Priya Bhupal, Sundar Kumar Veluswamy
Department of Physiotherapy, M S Ramaiah Medical College, Bengaluru, Karnataka, India
|Date of Submission||13-Dec-2020|
|Date of Decision||11-Feb-2021|
|Date of Acceptance||15-Mar-2021|
|Date of Web Publication||29-Jun-2022|
Sundar Kumar Veluswamy,
Department of Physiotherapy, M S Ramaiah Medical College, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
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.
Keywords: Biopsychosocial model, scrambler therapy, transcutaneous electrical nerve stimulation, World Health Organization analgesic ladder
|How to cite this URL:|
Verma R, Shivadeva M, Bhupal DP, Veluswamy SK. Looking beyond the obvious: Role of non-invasive electroanalgesia in management of cancer pain. Indian J Cancer [Epub ahead of print] [cited 2022 Aug 7]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=348451
| » Introduction|| |
Cancer pain is multifactorial and complex; it may arise out of the disease pathology, its treatment, or secondary complications. Despite the emergence of the biopsychosocial model of care, current strategies for the management of cancer pain predominantly use a biomedical approach. The World Health Organization (WHO) analgesic ladder suggests a sequential use of drugs, moving from non-opioids to strong opioids as a management strategy. The European Society for Medical Oncology and the Spanish Society of Medical Oncology clinical guidelines also recommend pharmaceutical management for cancer pain.
Pharmacological regimens have their own challenges; patients may exhibit varying sensitivities to the adverse effects associated with the long-term analgesic treatment, and alleviation of pain may require more than one analgesic. The type and extent of cancer may also limit the route of administration of analgesics in some patients. Various modifications, including a recent suggestion to reconfigure the WHO analgesic ladder to prioritize alternative invasive procedures over opioid administration, have also been observed.
Despite several proposed revisions to the analgesic ladder, the use of non-invasive electrical neurocutaneous stimulation techniques such as transcutaneous electrical nerve stimulation (TENS) and scrambler therapy as an adjuvant therapy have not found their place in the regimen. TENS is based on the “gate control theory” of pain, where surface electrodes stimulate A-beta fibers that inhibit pain transmission, whereas scrambler therapy focuses on stimulating C fibers and transforming the information of pain into “nonpain” using the same pathways via artificial neurons. In addition to being effective as pain control measures, TENS and scrambler therapy are also well tolerated with no serious adverse events and allow the user autonomy over their pain control. Anecdotal evidence from our clinical practice is suggestive of their effectiveness in the management of cancer pain. Through this perspective, we intend to provide an overview of the current literature with an aim to pique curiosity among the readers to consider the possible inclusion of non-invasive electroanalgesic options such as TENS and scrambler therapy as an adjuvant in treating cancer pain.
For this opinion piece, we chose to examine all articles identified by a combination of several databases, including PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar. Search terms, including “Scrambler Therapy,” “Calmare Therapy,” “TENS,” and “Cancer Pain” were used and combined using Boolean terminology. We were interested in identifying articles that showed the effects (both positive and negative) of TENS and scrambler therapy on cancer pain. Such articles were reviewed and reported with the analytical intent that was primarily descriptive.
In the absence of any importance attributed to non-invasive electroanalgesic approaches to cancer pain management in current clinical practice guidelines, we started with the premise that there would be scant evidence of benefits for such methods. Contrary to our expectations, the literature search yielded a significant number of studies that alluded to their benefit in the management of cancer pain. As we used an exploratory approach to screen for evidence of benefits, we were more inclusive in selecting articles and did not go by the standard approach of grading the quality of evidence as is usually performed in a systematic review. In brief, we identified and summarized 22 studies: 11 studies each pertaining to TENS and scrambler therapy. The studies exploring TENS and scrambler therapy varied in study design ranging from case reports, single-group pre-post design to randomized controlled trials (RCTs).
| » Studies on TENS|| |
The literature search identified a veritable mix of studies in an array of cancers. Details of the study characteristics and their findings are summarized in [Table 1]. Among the 11 studies identified, nine suggested improvements in varied parameters such as pain severity,,,,,,,,, reduced oral analgesic dependence,, chronic cancer pain, fatigue pain during movement and rest,, and quality of life. The two studies,, although found beneficial on other parameters, failed to demonstrate pain relief. They did not lead to aggravation of symptoms either, and no adverse events were reported by any of the studies.
| » Studies on Scrambler Therapy|| |
In the 11 studies identified through our search, all suggest positive benefits of scrambler therapy on cancer pain, the details of which are tabulated in [Table 2]. Moreover, the literature also suggests an improvement in chronic cancer pain not responding to pharmacological intervention, chronic postmastectomy pain and postlumpectomy pain, chemotherapy-induced neuropathic pain (CINP), and ultimately the quality of life. The included studies employed outcome measures such as visual analog scale, numeric pain rating scale, and modified questionnaires that have been validated in measuring pain and changes in quality of life in the cancer population. Scrambler therapy has varying degrees of efficacy with no substantial side effects. The limitations evidenced in the above literature arise from the lack of studies analyzing long-term effects of scrambler therapy.
|Table 2: Summary of Studies Using Scrambler Therapy for Management of Cancer Pain|
Click here to view
| » Our Perspective on the Use of Noninvasive Electroanalgesia in Management of Cancer Pain|| |
Maddening, unbearable, overwhelming, monstrous, and cruel are the descriptors patients with cancer ascribe to cancer pain. Cancer pain is underrecognized, underreported, and undertreated. Women suffering from pain after breast cancer treatment avoid taking medication because of concerns about unwanted side effects. Oral mucositis is cited as one of the most debilitating adverse effects of head and neck cancer treatment. Many patients suffering from oral mucositis have reported inadequate pain relief from topical medication. Inadequate analgesia and inevitable side effects from traditional pharmacological intervention elucidate the need for nonpharmacological treatment modalities to act as an adjuvant to the pre-existing protocol.
Nonpharmacological management of pain, both acute and chronic, has been long advocated as a strategy with physiotherapy practice. This approach has been supported by moderate- to high-quality evidence in patients with chronic pain of various origins. Non-invasive electroanalgesia is one such approach within the ambit of nonpharmacological interventions for pain along with more invasive techniques such as percutaneous electrical nerve stimulation, electroacupuncture, and spinal cord stimulation.
In this review, we have summarized the literature on the effectiveness of two such non-invasive neuromodulatory techniques: TENS and scrambler therapy. Although both use therapeutic electrical stimulation, they differ in their mode of action. TENS causes changes in the somatotopic organization in the parietal cortex resulting in increased attention to painful processes, which causes an inhibition in the transmission of the painful stimuli, whereas scrambler therapy replaces “pain” with “nonpain” signals resulting in an immediate reduction in pain with appropriate electrode placement. Relief from cancer pain through the use of non-invasive neuromodulatory techniques is documented across various cancer types and chronicity. Patients with head and neck cancers experienced ā reduction in mucositis pain at rest and bone pain during function, through the application of TENS. Scrambler therapy has shown improvement in CINP, and intense drug-resistant visceral pain. Also, these electroanalgesia methods present the added benefit of not overwhelming the body systems already burdened by the cancer treatment as they do not need to be metabolized and for the most part are easy to use and cost-effective.
WHO suggests quality of life as an important outcome measure in studies related to pain management. Scrambler therapy and TENS have reported improvement in the quality of life of the patients. Through 10 weeks of follow-up in a study, the Global Impression of Change scale showed improvement in quality of life through the application of scrambler therapy; another study suggested a reduction in pain interference with the use of TENS, extrapolating an improvement in the quality of life through their ability to perform activities of daily living without difficulty while using the machines.
Reduction in the adverse effects of cancer treatment is not limited to just pain. In patients with CINP, numbness and tingling are reported to be more bothersome than pain; scrambler therapy has been shown to have a positive effect on that as well., An overall improvement in general activity, mood, sleep, and enjoyment of life is also noted. A few studies noted the reduction in the analgesic intake and a complete cessation in one case. Physical, psychological, social, and environmental health was seen to show improvement post scrambler therapy.
Crucial facets of chronic pain management are autonomy, validation, and a sense of control. The benefit of talking to a health care professional about their pain cannot be overstated. Active participation of the patient in their treatment through the use of machines such as TENS encourages a self-management approach during a time when they need a sense of control the most.
These non-invasive electrotherapeutic approaches, much like the pharmacological approaches, are not without limitations. The analgesic benefits of TENS are the greatest during stimulation, but there are discrepancies in the longevity of the pain relief post-treatment, which warrants further research. Continuous stimulation also runs the risk of analgesic tolerance or habituation. For optimal analgesic effect, expertise in electrode placement is required during scrambler therapy; this is a necessity with TENS.
Limited clinical and academic interest in non-invasive neuromodulatory techniques, despite experts in the field elucidating the benefits of TENS in the management of cancer-related pain and studies indicating scrambler therapy's efficacy and safety in patients with pain not responsive to any treatments, particularly opioids, is a missed opportunity.
Research in the field of non-invasive electroanalgesia is still in its infancy. Long-term, large multicenter RCTs with a homogeneous sample are required, which can provide an avenue for future work in the area. Analyzing the longevity of the effects and construction of a precise application protocol for TENS and scrambler therapy in the cancer population using well-designed clinical trials and large multicenter RCTs can be considered for future research and would benefit the field.
| » Conclusion|| |
The existing literature provides us with a good starting point to consider non-invasive electroanalgesia as a means for controlling cancer pain, improving the functional abilities of these patients along with the adverse effects of cancer treatment, and ultimately improving their quality of life. Considering the benefit–risk relation, the inclusion of TENS and scrambler therapy in the treatment tool belt weighs heavily on the benefit side. A non-invasive, nonpharmacological approach is a promising complementary approach worth considering as a beneficial adjunct to the multimodal treatment of cancer pain.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Turk DC, Sist TC, Okifuji A, Miner MF, Florio G, Harrison P, et al
. Adaptation to metastatic cancer pain, regional/local cancer pain and non-cancer pain: Role of psychological and behavioral factors. Pain 1998;74:247-56.
World Health Organization. WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents. World Health Organization, Geneva. 2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537492/
Nersesyan H, Slavin KV. Current approach to cancer pain management: Availability and implications of different treatment options. Ther Clin Risk Manag 2007;3:381-400.
McGuire LS, Slavin K. Revisiting the WHO analgesic ladder for surgical management of pain. AMA J Ethics 2020;22:695-701.
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;18:1534735419845143.
Wen HL. Cancer pain treated with acupuncture and electrical stimulation. Mod Med Asia 1977;13:12-6.
Ostrowski MJ. Pain control in advanced malignant disease using transcutaneous nerve stimulation. Br J Clin Pract 1979;33:157-62.
Avellanosa AM, West CR. Experience with transcutaneous electrical nerve stimulation for relief of intractable pain in cancer patients. J Med 1982;13:203-13.
Robb KA, Newham DJ, Williams JE. Transcutaneous electrical nerve stimulation vs. transcutaneous spinal electroanalgesia for chronic pain associated with breast cancer treatments. J Pain Symptom Manage 2007;33:410-9.
Searle RD, Bennett MI, Johnson MI, Callin S, Radford H. Letter to editor: Transcutaneous electrical nerve stimulation (TENS) for cancer bone pain. Palliat Med 2008;22:878-9.
Bennett MI, Johnson MI, Brown SR, Radford H, Brown JM, Searle RD. Feasibility study of transcutaneous electrical nerve stimulation (TENS) for cancer bone pain. J Pain 2010;11:351-9.
Loh J, Gulati A. The use of transcutaneous electrical nerve stimulation (TENS) in a major cancer center for the treatment of severe cancer-related pain and associated disability. Pain Med 2015;16:1204-10.
Schleder JC, Verner FA, Mauda L, Mazzo DM, Fernandes LC. The transcutaneous electrical nerve stimulation of variable frequency intensity has a longer-lasting analgesic action than the burst transcutaneous electrical nerve stimulation in cancer pain. Revista Dor 2017;18:316-20.
Lee JE, Anderson CM, Perkhounkova Y, Sleeuwenhoek BM, Louison RR. Transcutaneous electrical nerve stimulation reduces resting pain in head and neck cancer patients: A randomized and placebo-controlled double-blind pilot study. Cancer Nurs 2019;42:218-28.
Gadsby JG, Franks A, Jarvis P, Dewhurst F. Acupuncture-like transcutaneous electrical nerve stimulation within palliative care: A pilot study. Complement Ther Med 1997;5:13-8.
Tonezzer T, Caffaro LA, Menon KR, Brandini da Silva FC, Moran de Brito CM, Sarri AJ, et al
. Effects of transcutaneous electrical nerve stimulation on chemotherapy-induced peripheral neuropathy symptoms (CIPN): A preliminary case-control study. J Phys Ther Sci 2017;29:685-92.
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;23:18-23.
] [Full text]
Smith T, Cheville AL, Loprinzi CL, Longo-Schoberlein D. Scrambler therapy for the treatment of Chronic post-mastectomy pain (cPMP). Cureus 2017;9:e1378.
Lee SC, Park KS, Moon JY, Kim EJ, Kim YC, Seo H, et al
. An exploratory study on the effectiveness of “Calmare therapy” in patients with cancer-related neuropathic pain: A pilot study. Eur J Oncol Nurs 2016;21:1-7.
Paice JA, Cohen FL. Validity of a verbally administered numeric rating scale to measure cancer pain intensity. Cancer Nurs 1997;20:88-93.
Marineo G. Untreatable pain resulting from abdominal cancer: New hope from biophysics. JOP 2003;4:1-10.
Smith TJ, Coyne PJ, Parker GL, Dodson P, Ramakrishnan V. Pilot trial of a patient-specific cutaneous electrostimulation device (MC5-A Calmare®
) for chemotherapy-induced peripheral neuropathy. J Pain Symptom Manage 2010;40:883-91.
Ricci M, Pirotti S, Scarpi E, Burgio M, Maltoni M, Sansoni E, et al
. Managing chronic pain: Results from an open-label study using MC5-A Calmare®
device. Supportive Care in Cancer 2012;20:405-12.
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;27:359-64.
Park HS, Sin WK, Kim HY, Moon JY, Park SY, Kim YC,. Scrambler therapy for patients with cancer pain-case series. Korean J Pain 2013;26:65-71.
Pachman DR, Weisbrod BL, Seisler DK, Barton DL, Fee-Schroeder KC, Smith TJ, et al
. Pilot evaluation of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy. Support Care Cancer 2015;23:943-51.
Park HS, Kim WJ, Kim HG, Yoo SH. Scrambler therapy for the treatment of neuropathic pain related to leukemia in a pediatric patient: A case report. Medicine (Baltimore) 2017;96:e8629.
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;65:e27064.
Stevens PE, Dibble SL, Miaskowski C. Prevalence, characteristics, and impact of postmastectomy pain syndrome: An investigation of women's experiences. Pain 1995;61:61-8.
Feng FY, Kim HM, Lyden TH, Haxer MJ, Feng M, Worden FP, et al
. Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: Early dose–effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys 2007;68:1289-98.
Howell SL. Natural/alternative health care practices used by women with chronic pain: Findings from a grounded theory research study. Nurse Pract Forum 1994;5:98-105.
Liebano RE, Rakel B, Vance CG, Walsh DM, Sluka KA. An investigation of the development of analgesic tolerance to TENS in humans. Pain® 2011;152:335-42.
[Table 1], [Table 2]