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. 2019 Jul 12;36(15):2372–2376. doi: 10.1089/neu.2018.6207

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© John C. Gensel et al., 2019; Published by Mary Ann Liebert, Inc.

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

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FIG. 2. — Pioglitazone (PIO) and azithromycin (AZM) alleviate spinal cord injury (SCI) pain in a sex-specific manner. Aged-matched (4-month-old) male and female mice received T9 75-kydn SCI. (A–C) A single intraperitoneal (i.p.) injection of PIO (10 mg/kg) was administered after the development of chronic pain (11 weeks post-SCI). (A) Analysis of the peak analgesia response (maximal withdrawal latency) revealed a significant sex × treatment interaction (p = 0.018) with significant improvements in female mice. (B) Treatment was only effective in female SCI mice (main effect of treatment, p < 0.05) versus male SCI mice (main effect of treatment, p = 0.4). PIO treatment significantly reduced pain responses in females at 30 and 60 min post-treatment. (D–F) A single dose of AZM (160 mg/kg) delivered by oral gavage (o.g.) was administered after the re-establishment of thermal hyperalgesia (2 weeks after PIO experiment in A; 13 weeks post-SCI). (D) Analysis of the maximal withdrawal latency recorded revealed no significant sex × treatment interaction (p = 0.49) with significant improvements in both female and male mice with AZM. (E and F) Treatment was effective in both female and male SCI mice (main effect of treatment by sex, p = 0.0008 and 0.0001, respectively). AZM treatment significantly reduced pain responses in females starting at 90 min post-treatment and in males at 60 min post-treatment (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001, Holmes-Sidak post-hoc after repeated-measures analysis of variance). Mean ± standard error of the mean, n = 7–8. BL, baseline.