Immediate Effects of Distinct Intensities of Transcutaneous Spinal Direct Current Stimulation on Chronic Pain: A Randomized Controlled Trial
, Arthur Ferreira EsquÃrio, Bianca Rossi Botim, Gabrielly Souza Jacob, Mayra Evelise Cunha dos Santos, Gabriela Lopes Gama, Michelle Cristina Sales Almeida Barbosa and Alexandre Wesley Carvalho Barbosa *Round 1
Reviewer 1 Report
Comments and Suggestions for Authors- The authors should further discuss why two different intensities of tsDCS resulted in similar effects and whether this implies an "optimal" stimulation intensity.
- The study lacks a control group (e.g., a sham group) or a standard group , which could reduce the pain of participants.
- The table presented in result could be modified.
Author Response
Dear Reviewer #1:
Thank you for your time to improve our manuscript. We acknowledge your efforts to help us in such a difficult task. Please, see our responses below. We hope they are in accordance to your guidance.
The authors should further discuss why two different intensities of tsDCS resulted in similar effects and whether this implies an "optimal" stimulation intensity.
ANSWER: Thank you for your comment. We added further explanation in our current version, highlighted in yellow. Please, refer to our current version.
The study lacks a control group (e.g., a sham group) or a standard group, which could reduce the pain of participants.
ANSWER: Thank you for your comment. For sure. We acknowledge as a limitation for our current findings.
The table presented in result could be modified.
ANSWER: We added another table to clarify the results.
Reviewer 2 Report
Comments and Suggestions for AuthorsThis manuscript investigates spinal tsDCS stimulation and its immediate effects on perceived pain using self-reported measures of the visual analog scale (VAS) and the pressure pain threshold response.
The number of participants is 55 which is substantial. There is no sham condition but two levels of stimulation instead, a low (0.5mA) and a high one (2mA).
A before vs after effects is evident in both groups but not between groups.
The article is very well written.
The introduction is well motivated and describes a real and costly problem for national health services.
There are some references to potential mechanistic bases for the effects but the discussion on mechanism is not in depth. My understanding is that mechanisms are still to be elucidated.
The study is well constructed and executed but there are some design features that weaken it. Specifically, the absence of a double-blind protocol and the absence of a sham condition. The reporting of the results is not complete.
Specific comments
When the authors say immediate effects, they should be clearer that they refer to assessments before after the cessation of the stimulation and not during. Maybe the title should be changed to ‘immediately after’…
How come there was data loss only in one condition? Were data collected by different experimental operators for each group? Were data collections intermixed or were 0.5mA done and then 2mA done after that? Please provide answers to the above and explain how the above observations may affect the data.
You ned to show the averages and error bars for the measured variables. Just showing the t-test is not enough information for the reader to judge the quality of the data. Please include a figure or two summarising the data.
Please discuss the possible use of independent measures of pain for more objectivity. Are there any that can be used? EEG? Other measures of automic activation?
The authors do mention that the absence of a sham (simulated) condition is a confounding factor here. Please emphasize this by mentioning the possibility of placebo effect being your actual measured effect being related to. Please change’simulated therapy’ to ‘sham therapy’ or ‘control ‘therapy’.
Explain the choice of 0.5mA. is this supposed to be subthreshold?
Finally comment on the absence of a double-blind protocol. If the operator of the algometer knows the level of stimulation it is possible to inadvertently/subconsciously bias the results.
Author Response
Dear Reviewer #2:
Thank you for your time to improve our manuscript. We acknowledge your efforts to help us in such a difficult task. Please, see our responses below. We hope they are in accordance to your guidance.
This manuscript investigates spinal tsDCS stimulation and its immediate effects on perceived pain using self-reported measures of the visual analog scale (VAS) and the pressure pain threshold response.
The number of participants is 55 which is substantial. There is no sham condition but two levels of stimulation instead, a low (0.5mA) and a high one (2mA).
A before vs after effects is evident in both groups but not between groups.
The article is very well written.
ANSWER: Thank you for your kind comment.
The introduction is well motivated and describes a real and costly problem for national health services.
There are some references to potential mechanistic bases for the effects but the discussion on mechanism is not in depth. My understanding is that mechanisms are still to be elucidated.
ANSWER: Thank you for your comment. We added some sentences trying to improve the clarity concerning the mechanistic theories involved in the present findings (highlighted in yellow). Please, refer to our current version.
The study is well constructed and executed but there are some design features that weaken it. Specifically, the absence of a double-blind protocol and the absence of a sham condition. The reporting of the results is not complete.
ANSWER: Thank you for your attention. We addressed those issues in our limitation section (highlighted in yellow).
Specific comments
When the authors say immediate effects, they should be clearer that they refer to assessments before after the cessation of the stimulation and not during. Maybe the title should be changed to ‘immediately after’…
ANSWER: Thank you for your comment. However, we followed other studies with the same objective. Thus, to preserve the meaning of the immediate effects, we opt to keep the title.
How come there was data loss only in one condition? Were data collected by different experimental operators for each group? Were data collections intermixed or were 0.5mA done and then 2mA done after that? Please provide answers to the above and explain how the above observations may affect the data.
ANSWER: Thank you for your attention. Data loss occurred due to patients asking to interrupt the protocol due to prone positioning. Thus, we were unable to perform the post-intervention data collection. However, in accordance to the CONSORT guidelines, we added the pre-assessment in our analysis to ensure the intention to treat analysis. Data were collected by the same rater. The allocation was randomized.
You ned to show the averages and error bars for the measured variables. Just showing the t-test is not enough information for the reader to judge the quality of the data. Please include a figure or two summarising the data.
ANSWER: Thank you for your comment. We included another table to show the central tendency and dispersion.
Please discuss the possible use of independent measures of pain for more objectivity. Are there any that can be used? EEG? Other measures of automic activation?
ANSWER: Sure. There are many other techniques for pain assessment. Unfortunately, due funding constraints, we did not perform other measurements. Recently, we added the Heart Rate Variability to our research, thus future studies will discuss those changes due to tsDCS.
The authors do mention that the absence of a sham (simulated) condition is a confounding factor here. Please emphasize this by mentioning the possibility of placebo effect being your actual measured effect being related to. Please change’simulated therapy’ to ‘sham therapy’ or ‘control ‘therapy’.
ANSWER: The placebo effect was mentioned in the current version. The simulated was changed to sham.
Explain the choice of 0.5mA. is this supposed to be subthreshold?
ANSWER: Yes. Thank you for your comment.
Finally comment on the absence of a double-blind protocol. If the operator of the algometer knows the level of stimulation it is possible to inadvertently/subconsciously bias the results.
ANSWER: Thank you for your comment. In fact, no. The technique to assess the PPT was to keep the LCD display in a blinded position (included in our current version). No rater bias during the PPT assessment was possible due to that. However, the study was not double-blinded because the rater knew what was being applied (0.5 or 2 mA)
Reviewer 3 Report
Comments and Suggestions for AuthorsA nice piece of work, however the outcome that 0.5 mA and 2.0 mA deliver almost the same measurable results contributes little to the state of the art - except that there is no Gold Standard to be found in this range (which is already described in [17]. I guess there are also no individual reports on subjective pain reduction (and the time the reduction prevails).
Question to the authors: Can the side effects (headache, electrode burning) be attributed to one of the groups?
Author Response
Dear Reviewer #3:
Thank you for your time to improve our manuscript. We acknowledge your efforts to help us in such a difficult task. Please, see our responses below. We hope they are in accordance to your guidance.
A nice piece of work, however the outcome that 0.5 mA and 2.0 mA deliver almost the same measurable results contributes little to the state of the art - except that there is no Gold Standard to be found in this range (which is already described in [17]. I guess there are also no individual reports on subjective pain reduction (and the time the reduction prevails).
ANSWER: Thank you for your comment. We expected differences to be noted. However, we are very engaged to the null hypothesis. We added more topics to our discussion to suggest some explanations for the present findings.
Question to the authors: Can the side effects (headache, electrode burning) be attributed to one of the groups?
ANSWER: Thank you for your comment. In fact, we had skin burning issues. However, we will discuss that in a further publication due to the importance of our findings.
