Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study

Gustavo A. Reyes del Paso; Pablo de la Coba

doi:10.1371/journal.pone.0241154

Peer Review History

Original SubmissionJune 13, 2020
17 Aug 2020 Decision Letter - Rayaz A Malik, Editor PONE-D-20-18091 Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study PLOS ONE Dear Dr. de la Coba, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. The observations are interesting, but the queries raised need to be addressed. Please submit your revised manuscript by Sep 27 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Rayaz A Malik, MBChB, PhD Academic Editor PLOS ONE Additional Editor Comments: You have made a simple and important additional finding in fibromyalgia which should be presented in a clear succinct manner. Consider the recent detailed paper showing widespread small fibre abnormalities in FMS by Evdokimov et al 2019;86: 504-516. Is there any relationship to the severity of FMS? Are the abnormalities noted comparable in the foot? Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please update the Methods section of your manuscript to include the following: A) Detailed inclusion and exclusion criteria for both cases and controls B) A rationale for the diagnosis of FM with the 1990 American College of Rheumatology criteria - please state why more recent diagnostic criteria were not used. C) Details of how participants were recruited to your study. 3. Please provide additional details regarding participant consent. In the Methods section, please ensure that you have specified what type of consent you obtained (for instance, written or verbal) and whether the ethics committee approved this consent procedure. If verbal consent was obtained please state why it was not possible to obtain written consent and how verbal consent was recorded. If your study included minors, state whether you obtained consent from parents or guardians. 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The authors describe an interesting study in patients with fibromyalgia. The data is fairly strong, although I have a couple of comments and questions for the authors. The testing is conducted on the right hand in all patients? In some places it is listed as the right hand, in other places as the dominant hand, can this be clarified? Could the authors explain why this was the location of testing? Sweating in the hands and feet has very strong associations with emotion, so carries a significant psychological impact on testing locations. QSART testing by multiple sites on not-emotional sweating locations would have derived a cleaner result. Skin conductance is a surrogate measure of sweat function, not a direct measure. Skin conductance is present in patients with a congenital absence of sweat glands, so there are significant limitations to what information can be extrapolated about the overall function of the autonomic system based on this limitation. The authors don’t really describe the individuals in this study. Were any of the fibromyalgia patients (or controls) taking medications? Did they have other medical conditions? These will create a huge impact on results and need to be included. The introduction is very long, and could be more focused. Some of the introduction could be moved to the methods or discussion section. As there is a limited amount of data in this paper, the authors do need to try and expand the value of this manuscript by adding additional figures or creating a multi-part figure with all the relevant data from the skin conductance during the different testing periods. ****** 6. 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Revision 1
8 Sep 2020 Author Response Dear Dr. Rayaz A Malik, Please find attached the revision of our manuscript entitled “Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study”. Changes are marked in yellow in the revision. Our responses to your comments and the reviewer´s comments are indicated below. Sincerely Pablo de la Coba Responses to the editor 1. Suggestion about the recent detailed paper showing widespread small fibre abnormalities in FMS by Evdokimov et al 2019;86: 504-516. Response: The suggested reference has been incorporated and discussed. Thanks for the suggestion. 2. Is there any relationship to the severity of FMS? Response: We have computed correlations between skin conductance variables and intensity of pain and fatigue in the whole sample. Significant negative associations were observed for the number of pain points, sensorial pain, current pain intensity and fatigue. Data on clinical symptoms and correlations of skin conductance with symptoms severity were included in the new version of the manuscript. 3. Are the abnormalities noted comparable in the foot? Response: We only measure skin conductance in the hand. We used the habitual psychophysiology protocol for recording skin conductance, which entail the localization of electrodes in the hand or the fingers. 1. Journal Requirements: Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response: Done. 2. Please update the Methods section of your manuscript to include the following: A) Detailed inclusion and exclusion criteria for both cases and controls Response: We have completed and specified the information about inclusion and exclusion criteria for the two study groups in the Participants subsection of the method. B) A rationale for the diagnosis of FM with the 1990 American College of Rheumatology criteria - please state why more recent diagnostic criteria were not used. Response: There were two main reasons to use the 1990 ACR criteria for FMS diagnosis in our study: 1) to unify diagnostic criteria, since there were several patients with a FMS diagnosis carried out before 2010; and 2) still currently in Spain, not all rheumatologists use 2010 ACR criteria, and several of them still uses the 1990 ACR criteria. We justify the use of the 1990 ACR criteria in the Participants section of the Method. C) Details of how participants were recruited to your study. Response: Additional information on the recruitment process has included in the Participants subsection of the method. 3. Please provide additional details regarding participant consent. In the Methods section, please ensure that you have specified what type of consent you obtained (for instance, written or verbal) and whether the ethics committee approved this consent procedure. If verbal consent was obtained please state why it was not possible to obtain written consent and how verbal consent was recorded. Response: We used a written consent. Additional details regarding participants consent and ethic committee approval have been added to the ending of Participant subsection of the method. 4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Response: The research data of the study are available to the public via the repository Open Science Framework (OSF: https://osf.io/3uk4e/). Responses to the reviewer The testing is conducted on the right hand in all patients? In some places it is listed as the right hand, in other places as the dominant hand, can this be clarified? Could the authors explain why this was the location of testing? Sweating in the hands and feet has very strong associations with emotion, so carries a significant psychological impact on testing locations. QSART testing by multiple sites on not-emotional sweating locations would have derived a cleaner result. Response: Testing was performed in all participants in the right hand. We have clarified this issue in the current version of the manuscript. We used for skin conductance recording the usual psychophysiology procedure for the measurement of levels and responses in which electrodes where located in the hands (the hands join with the feet are the body parts with more sweeting glands; Dawson, Schell, and Filion, 2016). In the protocol for the recording of electrochemical conductance, the only used body localizations are the hand and feet. We do not know studies in which skin conductance were recorded in other body parts. Skin conductance is a surrogate measure of sweat function, not a direct measure. Skin conductance is present in patients with a congenital absence of sweat glands, so there are significant limitations to what information can be extrapolated about the overall function of the autonomic system based on this limitation. Response: We are completely agree with the reviewer and we further emphasize this consideration in the limitation subsection of the discussion. The authors don’t really describe the individuals in this study. Were any of the fibromyalgia patients (or controls) taking medications? Did they have other medical conditions? These will create a huge impact on results and need to be included. Response: Based on the suggestion of the reviewer, and to better characterize our patients sample, we have included in Table 1 some clinical data of participants, including medication use. Most of the patients take different sets of medications, including antidepressants, anxiolytic, non-opioids analgesic and opioids. Unfortunately, due to the relatively small sample size of the study and the complex sets of used medications, the analysis of the potential effect of medications on skin conductance has been not possible. The power of statistical testing would not have been sufficient to compare the different subgroups of patients taking and not taking the different subsets of medications. As such, the effects of medication in the observed results cannot be ruled out. We have acknowledged this as the main limitation of the study in the revised Discussion as follow: “The main limitation of the study is medication use, as most of patients take different combinations of medications. Due to the relatively small sample size of the study and the complex sets of medications, the analysis of the potential effect of medication on skin conductance has not been possible. The power of statistical testing would not have been sufficient to compare subgroups of patients taking and not taking the different subsets of medications. As such, the effects of medication in the observed results cannot be ruled out. Future studies with larger sample sizes and ideally with patients free of medication should analyze this issue.” The introduction is very long, and could be more focused. Some of the introduction could be moved to the methods or discussion section. Response: The introduction section has been substantially shortened (several paragraphs have been omitted) and focused in the study aim. As there is a limited amount of data in this paper, the authors do need to try and expand the value of this manuscript by adding additional figures or creating a multi-part figure with all the relevant data from the skin conductance during the different testing periods. Response: Following the reviewer suggestion, we have included a new figure with the data of the response to the breathing manipulation and a table displaying the correlations. Furthermore, a table showing the correlations between skin conductance variables and pain and fatigue variables has been included. Dawson ME, Schell AM, Filion DL. The Electrodermal System. In: Cacioppo JT, Tassinary LG, Berntson GG. Handbook of Psychophysiology. Cambridge: University Press, Cambridge; 2016. pp. 217-243. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0241154.r002
9 Oct 2020 Decision Letter - Rayaz A Malik, Editor Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study PONE-D-20-18091R1 Dear Dr. de la Coba, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Rayaz A Malik, MBChB, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): All main comments have been addressed Reviewers' comments: https://doi.org/10.1371/journal.pone.0241154.r003
Formally Accepted
16 Oct 2020 Acceptance Letter - Rayaz A Malik, Editor PONE-D-20-18091R1 Reduced activity, reactivity and functionality of the sympathetic nervous system in fibromyalgia: An electrodermal study Dear Dr. de la Coba: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Rayaz A Malik Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0241154.r004

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