Chronic pain precedes disrupted eating behavior in low-back pain patients

Yezhe Lin; Ivan De Araujo; Gelsina Stanley; Dana Small; Paul Geha

doi:10.1371/journal.pone.0263527

Peer Review History

Original SubmissionJuly 9, 2021
1 Oct 2021 Decision Letter - Naim Akhtar Khan, Editor PONE-D-21-22332Chronic pain precedes disrupted eating behavior in low-back pain patientsPLOS ONE Dear Dr. Geha, 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 revise the MS in accordance to the Reviewers' comments. Please submit your revised manuscript by Nov 15 2021 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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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: Yes 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. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This is a well done study addressing a complex relationship between the hedonic qualities of food and chronic pain along with evaluation of the NAc. The findings are in many ways counter-intuitive and somewhat difficult to appreciate but have important implictions. The main suggestion is that the abstract should be re-written to provide the interpretation of the findings regarding the role of the NAc in disruption of hedonic quality in SBPr patients while a dysfunctional accumbens in the SBPp group protects them against disruption. It would also be helpful to provide better definition in many places in the manuscript of the term "disruption" - what exactly was being disrupted in the context of the sentence? It will also be interesting to see the outcomes of the proposed opioid studies. Reviewer #2: Yezhe Lin and collaborators have investigated whether Chronic pain precedes disrupted eating behavior in low-back pain patients This research is original and suggest that chronic pain precedes disrupted eating behavior in low-back pain patients and that such disruption is directly related to structural changes in nucleus accumbens. In spite of that, some aspects need to be clarified. Globaly , The manuscript is difficult to follow and deserves to be simplified or reorganized by example : - In Methods section, I suggest to include a schematic diagram describing the groups and procedures - Section results should be simplified and the figures numbers must follow as far as possible their order of quotation in the manuscript - In all the figures , bar graph shall be a contrasting colour - Legend of figure 2 (A-C) is omitted - Insert the groups in fig 2 and Fig 5 - A few tapping errors must be corrected ****** 6. 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Revision 1
6 Dec 2021 Author Response We would like to thank both reviewers for their interest in our work and their constructive feedback which helped improve the manuscript. Please find below point by point response to the reviewers comments. Reviewer #1: This is a well done study addressing a complex relationship between the hedonic qualities of food and chronic pain along with evaluation of the NAc. The findings are in many ways counter-intuitive and somewhat difficult to appreciate but have important implications. Thank you! The main suggestion is that the abstract should be re-written to provide the interpretation of the findings regarding the role of the NAc in disruption of hedonic quality in SBPr patients while a dysfunctional accumbens in the SBPp group protects them against disruption. As per the reviewer’s suggestion we re-wrote the abstract to provide the interpretation of the role of the NAc in the disruption of hedonic processing. We now write: Chronic pain is associated with anhedonia and decreased motivation. These behavioral alterations have been linked to alterations in the limbic brain and could explain the increased risk for obesity in pain patients. The mechanism of these behavioral changes and how they set in in relation to the development of chronic pain remain however poorly understood. Here we asked how eating behavior is affected in low-back pain patients before and after they transition to chronic pain, compared to patients whose pain subsides. Additionally, we assessed how the hedonic perception of fat-rich food, which is altered in chronic pain patients, relates to the properties of the nucleus accumbens in this patients’ population. We hypothesized that the accumbens will be directly implicated in the hedonic processing of fat-rich food in pain patients because of its well-established role in hedonic feeding and fat ingestion, and its emerging role in chronic pain. Accordingly, we used behavioral assays and structural brain imaging to test sub-acute back pain patients (SBP) and healthy control subjects at baseline and at approximately one-year follow-up. We also studied a sample of chronic low-back pain patients (CLBP) at one time point only. We found that SBP patients who recovered at follow-up (SBPr) and CLBP patients showed disrupted eating behaviors. In contrast, SBP patients who persisted in having pain at follow-up (SBPp) showed intact eating behavior. From a neurological standpoint, only SBPp and CLBP patients showed a strong and direct relationship between hedonic perception of fat-rich food and nucleus accumbens volume suggesting that accumbens alterations observed in SBPp patients in previous works might protect them from hedonic eating disruptions during the early course of the illness. We conclude that disrupted eating behavior specifically sets in after pain chronification and is accompanied by structural changes in the nucleus accumbens. It would also be helpful to provide better definition in many places in the manuscript of the term "disruption" - what exactly was being disrupted in the context of the sentence? We thank the reviewer for this suggestion. We tried to rephrase or explain the word disruption to be more specific all through the manuscript in the revised version. It will also be interesting to see the outcomes of the proposed opioid studies. We strongly agree with the reviewer on this future step. We are in the process of applying for funding to do these experiments. Reviewer #2: Yezhe Lin and collaborators have investigated whether Chronic pain precedes disrupted eating behavior in low-back pain patients This research is original and suggest that chronic pain precedes disrupted eating behavior in low-back pain patients and that such disruption is directly related to structural changes in nucleus accumbens. In spite of that, some aspects need to be clarified. Globaly , The manuscript is difficult to follow and deserves to be simplified or reorganized by example: - In Methods section, I suggest to include a schematic diagram describing the groups and procedures We thank the reviewer for this excellent suggestion. We now added a new figure (Figure 1) which depicts a schematic diagram describing the groups and the procedures. - Section results should be simplified and the figures numbers must follow as far as possible their order of quotation in the manuscript Per the reviewer’s suggestion we have now simplified the presentation of the results. We added a table (Table 4) to report the caloric intake separately from tables 1-3. We as much as possible now quote the figures in the order of their numbers. In addition we grouped supplementary tables 7-9 into one supplementary table 7 hence reducing the number of tables in the supporting information from 12 to 10. - In all the figures , bar graph shall be a contrasting colour. Per the reviewer’s suggestion we changed all the colors of all our figures to ensure an adequate contrast. - Legend of figure 2 (A-C) is omitted The legend of Figure 2 (now Figure 3) were inserted. - Insert the groups in fig 2 and Fig 5 We inserted the groups in Figures 2-5 which are now numbered Figure 3-6 because we added a new Figure 1. - A few tapping errors must be corrected Typing errors were corrected. Attachments Attachment Submitted filename: Response2Rev.docx https://doi.org/10.1371/journal.pone.0263527.r002
10 Jan 2022 Decision Letter - Naim Akhtar Khan, Editor PONE-D-21-22332R1Chronic pain precedes disrupted eating behavior in low-back pain patientsPLOS ONE Dear Dr. Geha, 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 Feb 24 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. 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 you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. 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, Naim Akhtar Khan, PhD, DSc Academic Editor PLOS ONE Additional Editor Comments: The MS has been revised as per comments of the reviewers. However, there are some linguistic errors in the MS. For example, in the revised version of the MS, in the Abstract section, sometimes, the principle clause is in past tense but the subordinate clause is still in the present tense. Please re-read the MS carefully and submit the new version for the final acceptance. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [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.0263527.r003
Revision 2
15 Jan 2022 Author Response We thank the reviewers and the editor for their critiques. We have now thoroughly corrected the linguistic errors in the manuscript. https://doi.org/10.1371/journal.pone.0263527.r004
21 Jan 2022 Decision Letter - Naim Akhtar Khan, Editor Chronic pain precedes disrupted eating behavior in low-back pain patients PONE-D-21-22332R2 Dear Dr. Geha, 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, Naim Akhtar Khan, PhD, DSc Academic Editor PLOS ONE Additional Editor Comments (optional): The revised MS is acceptable for the publication. Reviewers' comments: https://doi.org/10.1371/journal.pone.0263527.r005
Formally Accepted
2 Feb 2022 Acceptance Letter - Naim Akhtar Khan, Editor PONE-D-21-22332R2 Chronic pain precedes disrupted eating behavior in low-back pain patients Dear Dr. Geha: 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 Naim Akhtar Khan Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0263527.r006

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