Exploring pain interference with motor skill learning in humans: A systematic review

David Matthews; Edith Elgueta Cancino; Deborah Falla; Ali Khatibi

doi:10.1371/journal.pone.0274403

Peer Review History

Original SubmissionMarch 24, 2022
24 Jun 2022 Decision Letter - Yih-Kuen Jan, Editor PONE-D-22-06510Exploring pain interference with motor skill learning in humans: A systematic reviewPLOS ONE Dear Dr. Matthews, 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. Please submit your revised manuscript by Aug 08 2022 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. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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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 include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files. [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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: 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 Reviewer #2: 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 Reviewer #2: 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 systematically reviewed evidence on the impact of experimental and clinical pain on motor learning. Based on 18 studies included in the review, there was limited evidence of task performance changes due to pain. The paper is well written and the approach is appropriate but a few questions remain. Overall, how does the paper differ form recent work by Izadi et al., [1] examining motor learning in response to experimental pain models? Be sure to compare and contrast findings in discussion. Methods. 2.2.4. Outcomes. Why were activity dependent plasticity measures limited to amplitude, temporal, or spatial characteristics? Why were frequency domain measures not considered? 2.2.5. Study design. Why were studies including treatments as an adjunct to motor learning excluded? Wouldn’t those studies provide significant utility in evaluating potential mechanisms by which learning could be improved in the pretense of pain? 2.3. The search should be updated to reflect new papers published in the past year. Discussion. Be sure to discuss how findings compare and contrast with recent reviews [1,2] and findings in clinical pain [3]. Discuss limitations of current approach and how current findings compare with recent work. Literature Cited: [1] Izadi M, Franklin S, Bellafiore M, Franklin DW. Motor Learning in Response to Different Experimental Pain Models Among Healthy Individuals: A Systematic Review. Front Hum Neurosci. 2022;16:863741. Published 2022 Mar 24. doi:10.3389/fnhum.2022.863741 [2] Parker, Rosalind S., et al. "Is motor cortical excitability altered in people with chronic pain? A systematic review and meta-analysis." Brain stimulation 9.4 (2016): 488-500. [3] Brown, Michael R., Kirkwood E. Personius, and Jeanne Langan. "Participants with mildly-disabling chronic neck pain perform differently during explicit compared to implicit motor learning of a reaching task." PloS one 17.4 (2022): e0266508 Reviewer #2: The authors systematically reviewed the literature to explore the impact of pain on motor skill learning. However, the review suggests that there was no impact of pain on any task performance measures due to the limited evidence and heterogeneity. MAJOR COMMENT Introduction 1. Line 81-84: In my opinion, a brief introduction to the three pain paradigms and various motor paradigms might be needed to enable the readers to understand the differences. Discussion 2. Line 404-406: I recommend the authors elaborate more on how somatosensory feedback affects task performance. 3. In my opinion, the experimental pain (especially the way to apply capsaicin) would not really damage the human tissue but other ways might cause some injuries, which might result in different physiological changes. The evident difference should be noted and discussed. 4. Line 415-416: It is interesting that the increased attention of participants caused by pain might facilitate task performance. Is that possible that other sensory inputs would cause similar results? 5. In the clinical pain studies, were they all acute pain or chronic pain? Acute pain (eg. acute ankle sprain) and chronic pain (eg. osteoarthritis) might influence motor learning a lot. Much evidence has pointed out that chronic pain would change the excitability level or activation area of the cerebral cortex. I recommend the authors could put the related findings in the discussion. MINOR COMMENT Table 1 and Table 2. Please provide the full term for abbreviations in the footnotes like Table 3. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0274403.r001
Revision 1
8 Aug 2022 Author Response Further details of response can be found in 'Response to reviewers' file uploaded. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Authors response: Changes made to title page and formatting of titles. File naming uploaded as per guidelines on PLOSone website. 2. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files. Authors response: All tables uploaded to manuscript. Supplementary figures and tables uploaded separately. Titles of supplementary material added to bottom of manuscript. 3. How does the paper differ from recent work by Izadi et al., [1] examining motor learning in response to experimental pain models? Be sure to compare and contrast findings in discussion. Be sure to discuss how findings compare and contrast with recent reviews [1,2] and findings in clinical pain [3]. Discuss limitations of current approach and how current findings compare with recent work. Authors response: Two systematic reviews (Izadi et al. (2022) and Stanisic et al. (2022) have been published in this research area since the original submission of this manuscript. The below comments have been added to the introduction and discussion to reflect this and discuss the different methodological approaches and review findings. A discussion around the impacts of pain on cortical excitability has been adapted. The findings of the article mentioned by the reviewer [2] exploring the impact of chronic pain on cortical excitability (Parker et al 2016) has been considered when interpretating the results of this review. A section on limitations has been added to the discussion. 4. Why were activity dependent plasticity measures limited to amplitude, temporal, or spatial characteristics? Why were frequency domain measures not considered? Authors response: Activity measures were not limited to amplitude, temporal or spatial measures and the method has been adjusted to reflect this. No frequency domains of SEPs were explored as a measure in any included study and therefore no further discussion on this was deemed appropriate. To clarify this a sentence was added to the results. 5. Why were studies including treatments as an adjunct to motor learning excluded? Wouldn’t those studies provide significant utility in evaluating potential mechanisms by which learning could be improved in the pretense of pain? Authors response: Scoping searches prior to the preparation of the systematic review protocol revealed two studies including other treatments alongside motor learning tasks. These included; manipulation (Baarbe et al., 2018) and repeated peripheral magnetic neurostimulation (Massie-Alarie., 2017). The authors agreed including these articles would add to the existing diversity of the reviews methods which would impact on the ability for the review to provide coherent summary of research in this area for readers. 6. The search should be updated to reflect new papers published in the past year. Authors response: Search updated to July 2022, see line 138. Two further studies found meeting the criteria and included in the analysis. Two systematic reviews exploring similar research questions were found and these were included in the intro and discussion (see point 3). 7. Line 81-84: In my opinion, a brief introduction to the three pain paradigms and various motor paradigms might be needed to enable the readers to understand the differences. Authors response: Definitions of pain paradigms added to text and motor learning definitions included in new table (Table 1). Line 118. 8. Line 404-406: I recommend the authors elaborate more on how somatosensory feedback affects task performance. Authors response: Further research exploring the impact of somatosensory feedback/processing is added to the discussion including changes at different levels of the sensory pathway. 9. In my opinion, the experimental pain (especially the way to apply capsaicin) would not really damage the human tissue but other ways might cause some injuries, which might result in different physiological changes. The evident difference should be noted and discussed. Authors response: Capsaicin models were included in this study and were not considered to be a paradigm that may result in tissue damage. The method outlines those pain paradigms that were excluded due to be associated with potential changes in the muscle tissue such as DOMS (related to micro tears in the muscle and a healing process) and neurological disease (associated with reduced neural drive and associated muscle wasting). The authors agree clinical pain studies can be associated with tissue damage. This is highlighted during discussions around ROBIN-I, risk of bias and future studies. Musculoskeletal/neurological changes associated with the pain conditions could act as confounding variables. A lack of screening of clinical pain populations at baseline for the above confounding variables was a key determinant of the serious risk of bias judgements and subsequent exclusion of those studies from further analysis. The remaining two clinical pain studies included for further analysis did not differ in terms of baseline measures related to motor and sensory testing and therefore further discussions on this was not included. 10. Line 415-416: It is interesting that the increased attention of participants caused by pain might facilitate task performance. Is that possible that other sensory inputs would cause similar results? Authors response: The following paragraph was adapted for clarity, the research referred to when exploring impact of attention on neuroplastic changes used non-noxious sensory stimuli or auditory commands. A further question posed at the end of this paragraph is whether the attentional changes are a result of the painful stimulation or any sensory information and the importance of choice of control groups to explore this. 11. In the clinical pain studies, were they all acute pain or chronic pain? Acute pain (eg. acute ankle sprain) and chronic pain (eg. osteoarthritis) might influence motor learning a lot. Much evidence has pointed out that chronic pain would change the excitability level or activation area of the cerebral cortex. I recommend the authors could put the related findings in the discussion. Authors response: The two included clinical studies after quality assessment were both chronic pain paradigms and this has been added to the discussion. The studies found no effect of chronic pain on learning and therefore does not suggest differences between chronic and experimental acute pain effects on learning. A caveat to this, stated in the discussion, is sub-groups of chronic pain patients such as neuropathic pain may have different interactions with learning and chronic pain and acute pain mechanisms differ. The 3 clinical pain studies removed from the narrative review all explored different types of chronic pain with only one study demonstrating impact on motor learning. As mentioned previously as sensory and motor symptoms were not collated in these studies it is difficult to subgroup these studies. Worth noting one of these studies looked at osteoarthritis of the thumb and found no change in behaviour learning outcomes resulting from motor learning. In response to the comment stating chronic pain changes excitability of the cortex, two systematic reviews (including Parker et al 2016) are presented in the discussion which conclude that there is evidence of no impact of chronic pain on single pulse measures of cortical excitability but possibly changes in intracortical inhibition. 12. Table 1 and Table 2. Please provide the full term for abbreviations in the footnotes like Table 3 Authors response: Footnotes/abbreviations added to all tables. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0274403.r002
28 Aug 2022 Decision Letter - Yih-Kuen Jan, Editor Exploring pain interference with motor skill learning in humans: A systematic review PONE-D-22-06510R1 Dear Dr. Matthews, 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, Yih-Kuen Jan, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. 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: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. 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 Reviewer #2: Yes ****** 5. 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 Reviewer #2: Yes ****** 6. 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 have more than adequately addressed my comments. No further questions remain at this time. Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0274403.r003
Formally Accepted
2 Sep 2022 Acceptance Letter - Yih-Kuen Jan, Editor PONE-D-22-06510R1 Exploring pain interference with motor skill learning in humans: A systematic review Dear Dr. Matthews: 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 Dr. Yih-Kuen Jan Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0274403.r004

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