Content of review 1, reviewed on January 27, 2020

In the manuscript titled “Overexpression of miR138 ameliorates spared sciatic nerve injury induced neuropathic pain through anti-inflammatory response in mice" the authors hypothesize that miR138 contribute to the development of neuropathic pain, probably through regulating inflammatory reactions tDCS. It is an interesting study I don't believe the study brings value to the field. In addition, I think that this paper is poorly written, and it is not suitable for publication in the Journal of Pain Research. Please consider below specific points that require attention: Comments: 1) Abstract (conclusion): The authors should discuss their results better. Is too much general, maybe they could improve it. 2) Introduction: 1. In the M&M the authors described the measure of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-6 and nuclear factor-κB (NF-κB); however they did not mention anything about these biomarkers in the introduction of the manuscript. What is the relationship these variables with the proposed study? 2. The objective is not described in the introduction the same way that in the abstract. 3. Check many typing errors, for example, “caner” instead of cancer, and “contorl” instead of control, among others.

3) Methods 1. It is necessary to insert the following clarifications at Methods section: 2. What was the total number of animals used? 3. The authors should clarify the random assignment process of the animals, and clarify number of rats per cage in this study. The manuscript does not clearly articulate this. 4. Experimental design- the authors do not report the experimental design of the study in the methodology. Please insert the experimental design section in the manuscript and their respective experimental groups. Furthermore, please insert a timeline figure

explains when the treatment started, treatment time and test schedule with their respective analyzes. 5. Blinding- there is little information about study blind in the methods. What steps have been taken to control possible measurement bias? This should be better reported. Please, suggest inserting a blinding section with the appropriate explanations in the methods. 6. Why was not a control group used? This group could be very important since miR138 is related to inflammatory response, which may be altered in sham group. 7. In the same way, It would be important that the sham group was divided in two groups, one received the Intrathecal injection of LV-miR-control and another, LV- miR138. Why were not used the treatments in the two sham groups? 8. What was number of approval at Ethics Committee. 9. Specify the hydrochloride used. 10. Check some references inside the sentences. The list of references needs to be revised. 11. Where were the vehicle of LV-miR138 purchased? 12. It is important to better the description of intrathecal injection Technique. 13. How were the behavioral measures used obtained? I think that they were obtained from the mean average of the three measures realized; however, this must be clarified in the text. 14. How were expressed the results from MWT and PWL, in grams and seconds, respectively? Please, can you clarify it in the text? 15. How were the level cytokines expressed, as μg/mg? 16. What was the Statistical package used? 17. How were expressed the results, mean+SEM? 18. How were mice killed? 19. Where data the authors used two way ANOVA? 20. In the evaluation in many times it is appropriated the use of tests for data paired as measure repeated ANOVA or GEE.

4) Results 1. All Figures are with low resolution. 2. The results should be better structured. They are poorly written. 3. Revise the description of the behavioral results. It is very confusing.

  1. The authors should separately describe the behavioral results of those evaluating the expression of miR138, and the correlation between the two parameters.
  2. It is necessary to insert in the results the statistical tests used.
  3. Why did not the authors expose the values of degrees of freedom? Please insert this information into the description of the results.
  4. It is necessary to insert in the legends the statistical tests used.

5) Discussion 1. The authors suggest a miR138 therapeutic effect on the neuropathic pain, which probably relied on its anti-inflammatory ability because the administration miR138 before the surgery suppressed the production of pro-inflammatory factors, and the activation of astrocytes and microglia in spinal cord. However, as the administration miR138 was before the neuropathic pain induction, its effect is prophylactic and not therapeutic. To infer that the effect is therapeutic, its use should be after the establishment of neuropathic chronic pain. The author could be to suggest that miR138 is important to prevent the establishment of neuropathic chronic pain, being then, the miR138, a protective factor for pain. 2. Conclusion of the study: please explain what is novel about your study? Please re- write the conclusion session and include a sentence that states the implications of the present data. Specify how this study may contribute to clinical research. 3. I strongly recommend a review of all the manuscript made by a native English speaker.

Source

    © 2020 the Reviewer (CC BY 4.0).

References

    Benfan, Z., Jie, G., Yeling, O., Zhiqiang, H., Xiangdong, C. 2019. Overexpression Of miR 138 Ameliorates Spared Sciatic Nerve Injury-Induced Neuropathic Pain Through The Anti-Inflammatory Response In Mice. Journal of Pain Research.