PONE-D-23-34005Restoration of normal central pain processing following manual therapy in nonspecific chronic neck painPLOS ONE

Dear Dr. Zabala,

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.

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ACADEMIC EDITOR: Three expert reviewers assessed the manuscript. Although they have considered this manuscript, they have raised some significant comments and feedback. In my opinion, the inclusion of those comments will greatly enhance the quality of this manuscript. Furthermore, I have a few comments and recommendations as well.

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Please submit your revised manuscript by Feb 02 2024 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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We look forward to receiving your revised manuscript.

Kind regards,

Shahnawaz Anwer, PhD

Academic Editor

PLOS ONE

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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: Partly

Reviewer #3: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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

Reviewer #3: No

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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

Reviewer #3: Yes

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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: A single cohort study was conducted which aimed to investigate whether a 4-week manual therapy treatment intervention restores normal functioning of central pain processing mechanisms in non-specific chronic neck pain. In addition, the relationship between changes in pain processing mechanisms and clinical outcome was assessed. The study showed an increase in CPM response and TSP. Weak associations were found between TSP/CPM measures and clinical outcomes.

Minor revisions:

1- Abstract: State the statistical testing methods and summary statistics or p-values to support the results.

2- Line 111: Indicate the statistical method which achieves 80% power. The power calculation should include: (1) the estimated outcomes in each group; (2) the α (type I) error level; (3) the statistical power (or the β (type II) error level); (4) the target sample size and (5) the statistical testing method and (6) for continuous outcomes, the standard deviation of the measurements.

3- The standard statistical term for average is mean.

4- Line 197: Label this section, “Statistical Analysis”.

5- Line 197: Indicate the underlying covariance structure used in the generalized linear mixed model and the criteria for selecting it.

6- Table 2: In addition to the frequency, provide the percentage female.

7- Table 2: Indicate if the underlying distribution of the data in Table 2 was checked for normality.

Reviewer #2: Reviewer's Report:

Title: Restoration of normal central pain processing following manual therapy in nonspecific chronic neck pain.

Abstract:

1. Lack of Specific Results: The abstract mentions that "an increased CPM response and attenuated TSP were found," but it does not provide specific quantitative results or effect sizes, making it difficult for readers to assess the significance of these findings.

2. Minor Associations: The abstract states that "only minor associations were found between normalization of TSP/CPM and measures of clinical outcome," which raises questions about the clinical significance of the observed changes in central pain processing.

3. Limited Information on Participants: It would be helpful to include some basic demographic information about the participants in the abstract to provide context for the study findings.

Introduction:

The introduction section provides valuable background information on the prevalence and challenges associated with non-specific chronic neck pain (NSCNP). However, there are some points to consider:

1. Lack of Clarity on Research Gap: While the introduction highlights the need for better understanding the mechanisms of manual therapy, it does not clearly specify the research gap or the specific questions the study aims to address.

2. Reference to Guidelines: The introduction mentions guidelines advocating exercise and manual therapy for NSCNP but does not provide specific references or citations, which could enhance the credibility of the claims.

3. Lengthy Background Information: The introduction contains extensive background information on the prevalence of neck pain, which, while informative, could be condensed for brevity.

Methods:

1. Sample Size Justification: The rationale for the sample size of 63 participants is based on the detection of a maximum difference of 10% in TSP and CPM measures, but it would be beneficial to provide more information on how this specific effect size was determined.

2. Lack of Control Group: The study lacks a control group, which makes it challenging to establish causation and attribute the observed changes solely to the manual therapy intervention.

3. Treatment Description: The methods describe the manual therapy intervention broadly but do not provide specific details about the techniques used or the treatment protocol, which limits the ability to replicate the study.

4. Statistical Analysis: While the statistical approach is mentioned, the methods could benefit from a more detailed explanation of the statistical models used and the rationale for choosing the Bayesian approach.

Results and Discussion

1. Lack of Control Group: One of the major limitations of this study is the absence of a control group. Without a control group, it is challenging to attribute the observed improvements in central pain processing and clinical outcomes solely to the manual therapy intervention. It is essential to account for the natural course of the condition and any potential placebo effects.

2. Weak Associations: The study reports very weak associations between changes in central pain processing mechanisms and clinical/psychological variables. This suggests that other factors or mechanisms might be at play in explaining the clinical improvement following manual therapy. The authors acknowledge this limitation but do not provide a more in-depth discussion on possible alternative explanations or mechanisms.

3. Methodological Differences: The authors mention methodological differences in stimulus types used in previous studies and the current study for evaluating central pain processing (TSP). However, the significance and potential implications of these differences are not discussed in detail in the Discussion section.

4. Implications for Clinical Practice: The manuscript could benefit from a more comprehensive discussion of the clinical implications of the findings. How can these results inform clinical practice, and what recommendations can be made for manual therapy in the treatment of NSCNP patients?

5. Sample Characteristics: The manuscript briefly mentions that the sample presented only mild baseline disability. This should be discussed more thoroughly, as it may have implications for the generalizability of the findings to the broader NSCNP population.

6. Limitations: The limitations section is somewhat brief. It would be beneficial to provide a more extensive discussion of the study's limitations, including the potential impact of the lack of a control group and the generalizability of the findings.

Conclusion: Authors did not written conclusion

Reviewer #3: The manuscript aims to investigate whether a 4-week manual therapy treatment restores normal central pain processing in non-specific chronic neck pain. While the topic is clinically relevant, the current manuscript requires clarity improvements to effectively convey necessary information to readers.

Language: Some sentences are lengthy and intricate, and simplifying them would enhance readability.

Title: The title could be more concise and directly convey the primary study outcome.

Abstract: It is recommended to specify the exact manual therapy techniques used in the abstract.

Introduction:

The references to previous studies in the manuscript lack specificity and detail regarding their methodologies and findings. The introduction and previous literature sections lack explicit mention of the manual therapy techniques employed in these referenced studies. Including specific details about the manual therapy techniques used in relevant studies is essential for providing context and understanding the existing body of literature. This addition would contribute to a more comprehensive and informed discussion of the background and rationale for the current study.

Method:

Inclusion/exclusion criteria should be presented in the text.

The rationale for choosing these specific techniques, their potential benefits for NSCNP, and details about why only one session was utilized need further clarification, ideally with the inclusion of figures.

The table format does not adhere to scientific writing standards, and

Include detailed information on questionnaire reliability and validity. If translated into your language, provide references for reliability and validity.

Discussion:

The discussion mainly repeats results without in-depth analysis or comparisons with previous literature. More extensive discussion on methodology, manual therapy techniques, and clinical applications is needed. The conclusion lacks clarity, and future research directions should be elaborated upon.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Sahar Boozari

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Attachments

Attachment

Submitted filename: Reviewers comments for neck pain study.docx

PONE-D-23-34005R1Restoration of normal central pain processing following manual therapy in nonspecific chronic neck painPLOS ONE

Dear Dr. Zabala,

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.

==============================

ACADEMIC EDITOR:Dear Authors!

While your revised manuscript read better, there are still some important comments raised by the reviewers. Please address all the reviewer comments carefully.

==============================

Please submit your revised manuscript by May 03 2024 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Shahnawaz Anwer, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Authors!

While your revised manuscript read better, there are still some important comments raised by the reviewers. Please address all the reviewer comments carefully.

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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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

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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

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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

Reviewer #3: No

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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

Reviewer #3: Yes

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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: Only one prior comment was not adequately addressed. in the sample size justification section, indicate the statistical testing METHOD which achieves 80% power.

Reviewer #2: Restoration of normal central pain processing following manual therapy in nonspecific chronic neck pain. Manuscript is written very well, methodology need more detail, study findings are very interesting There are a few points that need to be addressed. The study is good and very helpful for clinical Physical Therapy Health Professionals.

1- Abstract: Revised abstract sound good.

2- What was reason of high percentage of female participants with NSCNP, is there any reference supporting high prevalence of pain in female.

3- Methodology: Need more detailed procedure for manual therapy, like who did this procedure of mobilization, is it the same researcher, who evaluated pre-and post intervention outcomes or other, was he certified manual therapist with how many years of experience?

4- P-A mobilization with how many, thrust or oscillations in each direction.

5- Mobilization force was applied at spinous process or at transvers process, if so how did you identified or located these landmarks.

6- While giving mobilization force vertebra was stabilized for example C4-C5 vertebra there is hypomobility.

7- How did authors gave A-P mobilizations at cervical spine.

8- Please attach few pictures of manual therapy, placement of hands, direction of mobilization etc..

9- How did authors calculated sample size (63), please write formula.

10- How reliable and valid was the Questionnaire used in this study?

11- Findings are very interesting.

Thanks & Regards.

Reviewer #3: (No Response)

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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

Reviewer #3: Yes: Sahar Boozari

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[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.

Attachments

Attachment

Submitted filename: Review comments for- NSCNP- manual therapy-PLOSOne.docx

Restoration of normal central pain processing following manual therapy in nonspecific chronic neck pain

PONE-D-23-34005R2

Dear Dr. Zabala,

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.

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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,

Shahnawaz Anwer, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Authors are congratulated for their diligent work and significant revisions made based on the reviewer comments. Manuscript is significantly improved.

Reviewers' comments: