3.4 Multiple courses
Out of 219 total patients, 44 repeated treatment due to its effectiveness and lack of side effects. We analyzed this subgroup of patients to assess the pain trend over subsequent cycles. A mean NRS score of 6.27 (±2.25) at T0, 2.83 (±1.7) at T2, and 2.94 (±2.24) at T4 (P value < .0001) was recorded, with an absolute reduction of 3.44 between T0 and T2. Notably, the subgroup of 22 patients with NRS ≥7 and a mean NRS score of 8.11 (±1.21) at T0 reduced their pain NRS score to 3.23 (±2.0) at T2 and 3.68 (±2.50) at T4.
Of the 13 patients suffering from cancer pain, 11 had moderate-severe pain (NRS ≥4), and 9 severe pain at T0 (NRS ≥7). The 13 patients with cancer pain that repeated ST reduced their mean NRS score from 6.58 (±2.06) at T0 to 2.85 (±2.08) at T2 and to 2.92 (±2.14) at T4 with an absolute reduction of 3.73 (P value < .0001). Patients with severe cancer pain (NRS 7.67; ± 1.00) at T0 had a mean NRS score reduction of over 50% by T4. The 11 patients with moderate-severe cancer pain had a reduction in pain ranging from 7.23 (±1.37) at T0 to 3.18 (±2.14) between T0-T4.
The 31 patients with non-cancer pain who underwent a second treatment of ST reduced their mean NRS score from 6.15 (±2.35) at T0 to 2.82 (±1.55) at T2 and to 2.95 (±2.31) at T4. The non-cancer severe pain category (NRS ≥7) included 13 patients with a mean NRS score of 8.42 (±1.29) at T0, 3.08 (±1.99) at T2, and 3.77 (±2.77) at T4, with an absolute reduction of 5.34 between T0 and T2 (P value < .0001).
An evaluation of the time elapsed between the first and second cycle of ST showed that 31 patients repeated the treatment within 2 to 5 months of the end of the first cycle; in detail 7 patients repeated treatment after 1 month, 12 within 2 to 3 months, 8 after 4 months, and 3 after 5 months with no significant difference in the initial and final mean NRS score between first and second course of treatment (data not shown). Thirteen patients underwent second ST after 6 months, without any significant difference in the initial and final mean NRS score between first and second course of treatment (data not shown). Twenty-one patients (67.7%) repeated the second ST on the same site as the first. No side effects were observed in any of the 219 patients treated.
Patients suffering from chronic pain are usually difficult to treat with conventional therapy. In the last years, these patients have been tested for the effect of nerve stimulation, in particular ST, on which 37 studies are currently available. Our study is the second prospective study to have combined clinical experience, prospective single-arm clinical trials, a randomized open-label controlled trial and 2 blinded, randomized placebo-controlled trials.
Marineo first developed ST and reported successful results in 11 cancer patients in 2003. In 2012, Ricci et al published a trial on 82 (73 evaluable) prospectively treated patients, about half of whom had cancer-related pain. Mean NRS score reduced from 6.2 to 1.6 before and after treatment, respectively, and was 2.9 one month after treatment had finished. Similar results were seen in patients with and without cancer. When patients were asked whether they would repeat this treatment, 97% (71/73) said they would.
Other prospective trials on cancer patients with chemotherapy-induced peripheral neuropathy reported positive results similar to our study with a long-lasting pain reduction by about 50%. The pain was long reduced throughout follow-up and up to a period of 3 months.[15–20] Marineo published a randomized trial on 52 patients with neuropathic pain comparing ST to standard pharmacologic recommendations, obtaining statistically significant results for the ST group. Other studies have attempted to reproduce the same findings in neuropathic pain obtaining results from 28% pain reduction (due to lack of experience, intractable pain, concomitant therapy) to over 50% up to 3 months of follow-up.[22–26] As for our study, the total data show a statistically significant reduction in pain from T0 to T4 in all patients, confirming the literature results. A good response was also reached by both categories of patients with and without cancer pain from T0 to T2, with a maintenance response at T4. Better results were reached by cancer patients with severe pain.
Patients suffering from non-cancer pain obtained positive results, with almost up to 50% pain reduction maintained throughout follow-up. Patients with neuropathic pain, especially severe pain, who had had almost up to 50% pain reduction, maintained the pain reduction over time, confirming the data from the literature. For patients that had undergone a second cycle of ST, the good response to treatment was confirmed with over 50% response maintained over time and greater absolute reduction during follow up. In particular, if patients started the second ST within 2 to 5 months, they would report an initial lower and a final higher median NRS score than in the first treatment. It is noteworthy that several patients repeated the treatment within 2 to 5 months with statistically significant response over time. Patients who repeated ST after 6 months of the end of the first treatment had a higher median NRS score than in the first cycle also at the end of the follow-up. Our data confirmed the effectiveness of ST on chronic pain, especially in diseases that are difficult to treat, such as arthritis.
Cancer pain is more complex to treat with ST due to concomitant therapies such, as radiation therapy and chemotherapy. In fact, ST must often be discontinued or suspended due to chemotherapy-related side effects or other cancer-related complications. All the operators received specific training to deal with these critical issues.
We suggest that all new prospective studies perform a standardization of the patient selection. ST, however, showed many undoubted advantages, including the results obtained with repeated treatments, the patient optimal compliance, the reduction of the use of opioids, which led to fewer severe adverse events. Future research should focus on the factors related to response and repetition of treatment, the placebo effect, and maintenance therapy.
The data collected and analyzed showed a statistically significant impact of the treatment with ST maintained throughout follow-up in patients suffering from chronic pain of multiple nature. ST represents a complementary perspective for analgesic control thanks to its safety and non-invasiveness. The success of this technique greatly depends on the patient selection and the level of expertise of the operator. The literature data, however, are heterogeneous and not exhaustive on the long-term effectiveness of the treatment. For this reason, further research is needed to promote prospective studies on response maintenance over time.
The authors would like to thank Veronica Zanoni and Gráinne Tierney and for editorial assistance.
All authors contributed equally to this paper, read, and approved the final version of the manuscript for submission.
Conceptualization: Marianna Ricci, Marco Maltoni.
Data curation: Marianna Ricci, Laura Fabbri, Sara Pirotti, Nicola Ruffilli, Flavia Foca.
Formal analysis: Marianna Ricci, Laura Fabbri, Nicola Ruffilli, Flavia Foca, Marco Maltoni.
Investigation: Marianna Ricci, Laura Fabbri, Sara Pirotti, Nicola Ruffilli, Marco Maltoni.
Methodology: Marianna Ricci, Laura Fabbri, Flavia Foca, Marco Maltoni.
Resources: Marianna Ricci, Sara Pirotti, Nicola Ruffilli, Flavia Foca, Marco Maltoni.
Supervision: Flavia Foca, Marco Maltoni.
Validation: Marianna Ricci, Marco Maltoni.
Visualization: Marianna Ricci, Laura Fabbri, Sara Pirotti, Nicola Ruffilli, Flavia Foca, Marco Maltoni.
Writing – original draft: Marianna Ricci, Laura Fabbri, Flavia Foca, Marco Maltoni.
Writing – review & editing: Marianna Ricci, Marco Maltoni.
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Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
calmare therapy; cancer pain; chronic pain; neuropathic pain; non-cancer pain; scrambler therapy