Rethinking procedural pain in labor: A comparison of lidocaine injection techniques for epidural catheter placement assessed with an objective clinician-centric pain score—A double-blind randomized controlled trial

Lukas Croner; Plato Lysandrou; Haosheng Li; Andrew Devine; Tyler Balon; Yun Xia; Nasir Hussain; Yue Yu; Mahmoud Abdel-Rasoul; Marco Echeverria Villalobos; Alberto Uribe; Elvia Vera Miquilena; Ling-Qun Hu

doi:10.1371/journal.pone.0339664

Peer Review History

Original SubmissionJuly 30, 2025
3 Nov 2025 Decision Letter - Claudia Interlandi, Editor Dear Dr. Hu, 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 Dec 18 2025 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. 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'. 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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Additional Editor Comments : The work is interesting, but further clarification and enrichment are needed before it can be considered for publication. [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? Reviewer #1: Partly 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 Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: This was a pilot study to compare subcutaneous (SC) and intradermal (ID) lidocaine administration to evaluate lidocaine injection pain and its analgesic efficacy. As such, being a pilot, there was no formal statistical power analysis provided. It was basically proof of concept. Clinical characteristics were compared between the study groups using a two-sample t-test or Kruskal- Wallis test for continuous variables and Chi-square test or Fisher’s exact test for categorical variables. For primary aims and perhaps appropriately given the small sample size, Kruskal-Wallis tests were used to test if there was a difference in CPOT score following lidocaine injection between the two study groups. For secondary aims, Kruskal-Wallis tests were used to assess the difference between the study groups in CPOT and NRS scores following Tuohy needle insertion, NRS score following lidocaine injection, as well as patient satisfaction scores. For hemodynamics, linear mixed-effects models were used to account for repeated measurements. Please comment on any repeated measures results, if any. The results were for the most part obviously not statistically different. While overall pain scores (NRS, CPOT) and hemodynamic changes did not differ significantly between groups, subcutaneous injections resulted in statistically lower muscle tension. The limitations, one being sample size, were appropriately listed. Obviously, the investigators should caution the reader that the significant p-values, especially comparison of the muscle tension scores, should be interpreted with caution and should be mentioned in the limitations and challenges section. Reviewer #2: This is an interesting study evaluating different ways to inject lidocaine during labor. Major Comments 1. This is a very small study of 51 patients. The authors acknowledge this; however, I believe it is important to emphasize more clearly this major limitation. 2. The fact that such a small number of patients at a single center further underscores the major limitations of this study and the need for follow up study(ies) to confirm these preliminary results. ****** 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? 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Revision 1
26 Nov 2025 Author Response Response to Reviewers 1. Comment: 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 - Response: We have revised the manuscript to comply with PLOS ONE’s formatting guidelines for both the main text and title/author sections. 2. Comment: In the online submission form, you indicated that the de-identified dataset generated and analyzed during the current study is available from the corresponding author upon reasonable request. The study protocol and statistical code used for analysis are also available upon request. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Response: The de-identified raw dataset has been uploaded as Supporting Information in accordance with PLOS ONE’s data-sharing policy. All personal identifiers have been removed to ensure participant privacy. 3. Comment: We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Response: The funding details have been corrected and now match across the “Funding Information” and “Financial Disclosure” sections. 4. Comment: Please include a caption for figure 1. Response: A descriptive caption for Figure 1 has been added and the figure re-uploaded: “The above figure shows the randomization of 51 patients into two interventions: Intradermal Lidocaine (25 participants) and Subcutaneous Lidocaine (26 participants). All participants were analyzed according to original group allocation.” 5. Comment: Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Response: Titles and captions for all Supporting Information files have been included at the end of the manuscript, and in-text citations have been updated accordingly. 6. Comment: We note that there is identifying data in the Supporting Information file <Initial Submission Approved. Pdf, Initial Submission Approved Protocol. pdf>. Due to the inclusion of these potentially identifying data, we have removed this file from your file inventory. Prior to sharing human research participant data, authors should consult with an ethics committee to ensure data are shared in accordance with participant consent and all applicable local laws. Data sharing should never compromise participant privacy. It is therefore not appropriate to publicly share personally identifiable data on human research participants. The following are examples of data that should not be shared: -Name, initials, physical address -Ages more specific than whole numbers -Internet protocol (IP) address -Specific dates (birth dates, death dates, examination dates, etc.) -Contact information such as phone number or email address -Location data -ID numbers that seem specific (long numbers, include initials, titled “Hospital ID”) rather than random (small numbers in numerical order) Data that are not directly identifying may also be inappropriate to share, as in combination they can become identifying. For example, data collected from a small group of participants, vulnerable populations, or private groups should not be shared if they involve indirect identifiers (such as sex, ethnicity, location, etc.) that may risk the identification of study participants. Additional guidance on preparing raw data for publication can be found in our Data Policy (https://journals.plos.org/plosone/s/data-availability#loc-human-research-participant-data-and-other-sensitive-data) and in the following article: http://www.bmj.com/content/340/bmj.c181.long. Please remove or anonymize all personal information (<specific identifying information in file to be removed>), ensure that the data shared are in accordance with participant consent, and re-upload a fully anonymized data set. Please note that spreadsheet columns with personal information must be removed and not hidden as all hidden columns will appear in the published file. Response: All identifying information has been removed from the Supporting Information files. The uploaded dataset is fully anonymized and complies with participant consent and ethical standards. 7. Comment: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Response: We have addressed all reviewer suggestions: Clarified limitations, emphasizing the small sample size and single-center design. Added statements in the limitations section conclusion to caution interpretation of significant findings and highlight the need for larger studies: “Third, the CPOT was originally designed for use in critical care settings and has not been validated for assessing pain during labor and delivery procedures; its reliability in this context remains to be established, particularly comparisons of individual components, such as muscle tension alone” and “However, given small sample size, more research is necessary to validate these findings.” Clarified “repeat” measures for linear mixed effect models: “For hemodynamics, linear mixed-effects models were used to account for measurements at three time points per participant: baseline, after lidocaine injection, and after Tuohy needle insertion” Added clarifying statement to results: “Pairwise comparisons of hemodynamics were made between intradermal and subcutaneous injection techniques at three timepoints: baseline, after lidocaine injection, and after Tuohy insertion.” Also updated p-values in Table 4 for precision. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0339664.r002
10 Dec 2025 Decision Letter - Claudia Interlandi, Editor Rethinking Procedural Pain in Labor: A Comparison of Lidocaine Injection Techniques for Epidural Catheter Placement Assessed with an Objective Clinician-Centric Pain Score -A Double-Blind Randomized Controlled Trial PONE-D-25-38198R1 Dear Dr. Ling-Qun Hu, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . 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, Claudia Interlandi, Ph.D Academic Editor PLOS One Additional Editor Comments (optional): Thank you for the improvements made to the manuscript. It will now be considered for publication. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #1: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: (No Response) ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: (No Response) ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: (No Response) ****** Reviewer #1: (No Response) ****** 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 ******** https://doi.org/10.1371/journal.pone.0339664.r003
Formally Accepted
Acceptance Letter - Claudia Interlandi, Editor PONE-D-25-38198R1 PLOS One Dear Dr. Hu, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@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 Claudia Interlandi Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0339664.r004

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