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Article
Peer-Review Record

Sexually Dimorphic Immune and Neuroimmune Changes Following Peripheral Nerve Injury in Mice: Novel Insights for Gender Medicine

Int. J. Mol. Sci. 2021, 22(9), 4397; https://doi.org/10.3390/ijms22094397
by Valentina Vacca 1,2,†, Sara Marinelli 1,2,†, Federica De Angelis 1,2, Daniela F. Angelini 2, Eleonora Piras 2, Luca Battistini 2, Flaminia Pavone 1,2,* and Roberto Coccurello 2,3,*
Reviewer 1: Anonymous
Reviewer 2:
Int. J. Mol. Sci. 2021, 22(9), 4397; https://doi.org/10.3390/ijms22094397
Submission received: 9 March 2021 / Revised: 7 April 2021 / Accepted: 16 April 2021 / Published: 22 April 2021
(This article belongs to the Special Issue The Multiple Mechanisms Underlying Neuropathic Pain)

Round 1

Reviewer 1 Report

Dear Author,

The study is part of a project about peripheral nerve in mice, related to gender. 

The project is interesting and well written. I suggest to add the paragraph "material and methods" moving from the "results" the parte of the methods. 

Author Response

We would like to thank for the reviewer for his/her idea. Unfortunately, the format and arrangement of the manuscript is forced by the guidelines of the journal and not the result of author’s choice. In any case, following the suggestion received, we have now inserted in the results section some information introducing the methods utilized. All changes are now visible in bold text.

Reviewer 2 Report

Neuropathic pain remains a challenge for scientists. Gender difference is one critical factor for determining neuropathic pain. This paper provides novel insights into the understanding of immune profiles of sex difference in sciatic nerve and blood after CCI. The paper presents lots of information which are useful for the future research.

One major concern is the conclusion in Figure 1A. Although there is statistical significance in D3, D5 and D7, but there is no difference on D4 and D6. Does the author have other time point for longer time? It will be great that the author adds more evidence to support the conclusion about sex different, such as cold plate test, hot plate, or others to describe pain level.

Author Response

We would like to thank for the reviewer for his/her positive comments to our work. As for the first point, we would like to draw the attention to the fact that a longer time-course (from D3 to D21) has been showed in other papers (in the text as references #16 and #17). However, to improve the understanding and better specify the rationale underlying this option, we have now specified this point in the result section “2.1.1. Functional testing: sex-differences in mechanical nociceptive threshold.”

With regard to the second point, we have now included additional data about the measurement of thermal hyperalgesia, as proposed. The statistics is now in the same paragraph as above (2.1.1). Consequently, a new figure 1 is replacing the previous version. All changes are now visible in bold text.

Round 2

Reviewer 2 Report

The author has addressed my concerns.

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