Peer Review History
Original SubmissionOctober 12, 2020 |
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PONE-D-20-32048 Comparison of Analgesic Activities of Aconitine in Different Mice Pain Models PLOS ONE Dear Dr. Feng, 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 pay careful attention to the issues raised by the reviewers. Both reviewers were highly concerned about the rigor of experimental design and analysis, as well as the organization of the manuscript and the conclusions drawn from the data. A successful revision will take these issues strongly into account. Please submit your revised manuscript by Jan 22 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. Please include the following items when submitting your revised 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, John M. Streicher, Ph.D. Academic Editor PLOS ONE 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 2. To this end, please revise your Methods section to address the following: (1) the number of animals in each group and how you determined the sample size; (2) the sex and strain of the mice; (3) all anesthetics and analgesics administered to animals during your study (name of drug, dosage, frequency and route of administration); (4) details about humane endpoints for any animals who became severely ill or injured during the study; (5) the rate of mortality during the study and the cause of death (if applicable); (6) the criteria used to determine when to euthanize animals (for animals who became ill prior to the experimental endpoints). Lastly, please complete and submit the ARRIVE Guidelines 2.0 checklist (Essential 10 version): https://arriveguidelines.org/resources/author-checklists . 3. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ 4. 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 5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. [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: No Reviewer #2: Partly ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: I Don't Know ********** 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: No 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: No Reviewer #2: No ********** 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: This manuscript by Deng et al. aimed to determine the analgesic activity of aconitine (AC) on thermal and inflammatory pain. The authors performed hot plate test to determine the impact of AC on thermal pain, and then used the acetic acid-, formaldehyde-, and CFA-induced pain to test the effect of AC on inflammatory pain. They found that treatment with AC exhibited analgesic effects in those pain models. However, this is not a well-designed study and a poorly written manuscript. Major Compulsory Revisions 1) Provide the rationale for this study. What do the results mean? 2) Abstract: provide more specific information about methodology; the conclusion should be re-written. 3) Introduction: a. The whole section is a lack logic and needs to be organized. b. The statement addressed in Line 53-55 is incorrect. c. Add the reference for the statement in Line 61. 4) Methods: a. The purchased AC needs to be characterized to confirm. b. Provide more details about how the mice were housed; the temperature and humidity could induce some stress for the mice; the groups of animals are inconsistent (4 or 5 groups), and the name of groups are very confused (vehicle, normal, model) through the whole manuscript. c. Provide rationale for the dosage of AC since it has been demonstrated serious toxicity; please provide the reference of the authors’ previous study mentioned in Line 232. d. The description of doses of AC is inconsistent through the methods section. e. The description of methods is confusing, including Line 115-116, Line 121-123, Line 123-125, and Line 126-127. f. Please confirm that the formaldehyde and CFA were injected into the toes of mice; how many toes were injected? g. The impact of AC on the “normal group mice” should be included in the CFA and formaldehyde experiments. h. Provide the post-comparison method in the statistical analysis. 5) Results: a. The names of treatment groups are very hard to follow. b. Please define the “viz” (Line 151) and T1/2 (Line 168). c. The data from two doses of AC can NOT support any “dose (concentration)-dependent manner” effects, and the impact of the low and high dose of AC was very tight in most of the experiments. d. The authors mentioned indomethacin in Line 161, where is that from? Please clarify. e. Descriptions are confused, such as Line 169-170, Line 187-188, Line 188-190. f. Explain the statement in Line 186. g. Clarify the method used for determining the mechanical hyperalgesia (Line 194). h. The whole section from Line 198-218 is unnecessary. If the authors really want to keep it, then it should be merged into the discussion. i. Improve the quality of images in Figure 2A. 6) Discussion: a. Why do the readers need to know the information in Line 222-223? b. The acute treatment with acetic acid is hard to induce any neuropathic pain. It is unclear where the statement is in Line 240-242 from. c. It is a lack of evidence to support the statement in Line 256-257. 7) The whole manuscript needs to be edited by a native speaker of English. Reviewer #2: While the findings of this study are interesting, the conclusions that are drawn by the authors are somewhat inappropriate. There are also problems with the language used throughout the manuscript that make it difficult to understand. Specifically, in their conclusions statement of the abstract as well as in their discussion section, they state that ‘the analgesic effect of aconitine (AC) was that pain caused by acetic acid stimulation was greater than pain induced by heat stimuli, and acute inflammatory pain was greater than chronic inflammatory pain’. This statement is very confusing because they begin talking about the analgesic effect of AC and then they describe that pain was greater in some of their models. They should be describing the analgesic effect throughout their conclusion. They should also use the language of the specific assays/models that they used to measure the analgesic effect instead of the broad statement of acute inflammatory pain or chronic inflammatory pain. Additionally, in their discussion they compare the pain induced by heat stimuli to the pain of acetic acid stimulation and state that AC had stronger analgesic effect on the acetic acid test. This is not an appropriate comparison because the hot plate test is not a model of pain but rather an assay to measure heat withdrawal latency. The acetic acid test is used to evoke pain-like behavior and therefore there is much more room for an analgesic effect. The hot plate test was simply measuring heat withdrawal latency with nothing to evoke pain. The authors also consistently call the formalin model an acute pain model and the CFA model a chronic pain model and this is not entirely accurate. CFA injection does not necessarily cause chronic pain. As a suggestion for a more appropriate way to draw conclusions, the authors could simply state that AC had an analgesic effect in each of their pain models instead of ranking the analgesic effect and comparing it between the models, as all of the models were measuring different things. Other comments: Methods: In the ‘animals and treatment’ section of the methods the authors state that all animals were divided into 5 groups but it doesn’t state what these groups are. Were male or female mice combined in the assays? If so, were the sexes compared to see if there were differences between males and females? The hot plate test is not well described. The authors state ‘the latency of 30 minutes after administration was measured 3 times’ but do not describe what the latency is. Is it latency to withdraw paw? Also, the pain threshold improvement rate equation describes a base threshold but how and when this was measured is not described. In the formalin test, how were saline, aspirin, and AC given? In the formalin test, the authors state ‘after 60 and 120 min of administration, formalin was injected’. This language is confusing and makes it seem like the saline, aspirin, and AC were administered continuously for 60 and 120 minutes. In the formalin test, what is the cumulative time of lameness? Usually in the formalin test the amount of time spent licking the paw is quantified. There is nothing in the statistics section or in the figure/table legends about post-hoc analyses, which is where it appears the significance comes from. Results: The authors state in the formalin-induced paw licking model section: ‘AC administration for 120 minutes also significantly inhibited formalin-induced paw withdrawal time in a concentration-dependent manner’. Should this say licking time? Or was something else measured? Edema is not a measure of pain but a measure of swelling, which is often associated with inflammation and commonly measure following CFA injection. This language should be changed to reflect this. The authors state that ‘this-CFA induced mechanical hyperalgesia was inhibited by administration with AC’, however they are measuring thermal hyperalgesia. Why in the CFA model are the mice treated multiple times with AC when in the other tests they are only treated once? Discussion The sentence ‘As far as we know, AC has a wide range of analgesic properties, but whether there is a difference in the treatment among pains by AC, and which kind of pain has the best therapeutic effect have not been demonstrated in reports.’ Is very confusing and not worded well. The statement about the concentration of AC that was previously found should be in the methods section somewhere. There could be some discussion as to why in the CFA model, the lesser dose of AC seemed to work better than the higher dose of AC but the higher dose of AC worked better in the formalin model and the writhing pain and hot plate (slightly) Figures and tables: The figures and tables 1 & 2 look nice and are organized well. The tables would be more compelling as figures. The figure 1 legend says the administration of AC or aspirin for 60 (or 120) minutes- does this mean given 60 minutes before? In Figure 2, were there actual measurements of edema taken or just pictures? In the Figure 2A legend, they mention the analgesic effect of aconitine but only edema is shown, not analgesia In Figure 2 need to state what the test is in Figure 2B- says contraction latency but not from the hotplate test ********** 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. |
Revision 1 |
PONE-D-20-32048R1 Comparison of Analgesic Activities of Aconitine in Different Mice Pain Models PLOS ONE Dear Dr. Feng, 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 Mar 25 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. Please include the following items when submitting your revised 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, John M. Streicher, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (if provided): Thank you for your revised submission. Both Reviewers still had minor comments that need to be addressed. If you can address these, I can make the final decision without further rounds of review. Thank you! [Note: HTML markup is below. Please do not edit.] 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) ********** 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: (No Response) Reviewer #2: Partly ********** 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: No 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 manuscript has been improved in the revised version. However, several major issues remain to be improved. Major Compulsory Revisions 1) The authors only changed the format of the abstract but not really address the comments brought up in the primary evaluation. 2) Introduction: This section is still not logically described and needed to be improved. 3) Methods: The “model” group is the same treatment as the “control” group based on the information in Line 137-138 and Line 147-148. 4) Results: The low dose of AC showed the most significant improvement based on the images of the hind paw in Figure 2. However, the bar graph doesn’t indicate that. 5) The English language issue still needs to be improved throughout the whole manuscript. Reviewer #2: The authors have appropriately addressed my original comments but the revised version has a few things that need to be addressed. 1. In the abstract (line 27) the authors state they are looking at the analgesic activities of AC on neuropathic pain. However, they do not use a neuropathic pain model. This should be revised to say they are looking at the analgesic effects of AC on thermal sensitivity, or something similar. 2. Similarly, in the abstract (line 38) they state AC had analgesic effect on neuropathic pain but they only use the hot plate to measure thermal sensitivity in naive mice, not a neuropathic pain model. Please revise this sentence as well. 3. The use of the word 'videlicet' in line 169 does not seem appropriate 4. The sentence ending on Line 236 would make more sense if it read '48 hours after CFA injection' instead of 'after CFA injection 48 hours' 5. The conclusion drawn in lines 236-238 is not accurate unless the the different time points following CFA injection were compared statistically. From figure 2, it does not appear that the different time points were compared, only the different groups. 6. The wording of the conclusion on line 267 that AC was able to relieve neuropathic pain is inappropriate (similar to comments 1 and 2). This should say thermal sensitivity or something similar. 7. Lines 282-283 also mention AC having an effect on neuropathic pain 8. In Table 3 for the CFA induced nociception assay, what does the 7th compare with 1st value mean? ********** 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 [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. |
Revision 2 |
Comparison of Analgesic Activities of Aconitine in Different Mice Pain Models PONE-D-20-32048R2 Dear Dr. Feng, 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, John M. Streicher, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: |
Formally Accepted |
PONE-D-20-32048R2 Comparison of analgesic activities of aconitine in different mice pain models Dear Dr. Feng: 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. John M. Streicher Academic Editor PLOS ONE |
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