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. 2021 Oct 11;11(10):1339. doi: 10.3390/brainsci11101339

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Inter-individual and sex differences in neuropathic pain-related behaviors of FE+ and FE− rats. (A) Mechanical thresholds tested in sham and chronic neuropathic SNL rats (4 weeks post-induction) showed no significant differences between FE− (female, n = 26; male, n = 32) and FE+ (female, n = 35; male, n = 40) sham rats or between FE− (female, n = 9; male, n = 14) and FE+ (female, n = 20; male, n = 17) SNL rats, but SNL FE− and FE+ rats had significantly lower withdrawal thresholds than their sham controls. **** p < 0.0001, ANOVA with Bonferroni post hoc tests (see the “Results” section). (B,C) Duration (s) of of ultrasonic and audible vocalizations, respectively, evoked by a brief (10 s) noxious (1500 g/6 mm²) mechanical compression of the affected hindpaw. Significant differences in ultrasonic and audible vocalizations were found between female FE− (n = 15) and FE+ (n = 20) SNL rats but not between male FE− (n = 15) and FE+ (n = 15) SNL rats or between FE− (female, n = 26; male, n = 32) and FE+ (female, n = 38; male, n = 41) sham rats. For both sexes, SNL rats had significantly increased vocalizations compared to their sham controls. n.s.: non-significant; ⁺ p < 0.05; ^# p < 0.05; ^### p < 0.001; ^#### p < 0.0001; **** p < 0.0001, ANOVA with Bonferroni post hoc tests (see the “Results” section). (D) Center duration (s) in the OFT was significantly lower in FE− (female, n = 9; male, n = 13) and FE+ (female, n = 20; male, n = 20) SNL rats compared to their FE− (female, n = 19; male, n = 12) and FE+ (female, n = 33; male, n = 22) sham controls. No differences were found between FE− and FE+ rats in the sham or SNL groups for either sex. ^#### p < 0.0001; * p < 0.05; ** p < 0.01; **** p < 0.0001, ANOVA with Bonferroni post hoc tests (see the “Results” section). Bar histograms show means ± SEM. FE: fear extinction; OFT: open field test; SNL: spinal nerve ligation. Asterisk (*) indicates comparison to untreated group; plus sign (+) indicates comparison between phenotypes; pound sign (#) indicates comparison between sexes.