Sexual Dimorphism of Pain Control: Analgesic Effects of Pioglitazone and Azithromycin in Chronic Spinal Cord Injury

John C. Gensel, Renée R. Donahue, William M. Bailey, Bradley K. Taylor

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Central neuropathic pain develops in greater than 75% of individuals suffering a spinal cord injury (SCI). Increasingly, sex is recognized as an important biological variable in the development and treatment of peripheral neuropathic pain, but much less is known about the role of sex in central neuropathic pain and its pharmacological inhibition. To test the hypothesis that efficacy of analgesic therapies differs between males and females in SCI, we used a mouse model of SCI pain to determine the analgesic efficacy of pioglitazone (PIO), U.S. Food and Drug Administration-approved drug for the treatment of diabetes, and azithromycin (AZM), a commonly prescribed macrolide antibiotic with immunomodulatory properties. Male and female mice received moderate-severe T9 contusion SCI (75-kdyn). A robust heat hyperalgesia developed similarly between male and female mice by 4 weeks post-injury and lasted throughout the duration of the study (14 weeks). Three months after SCI, mice were treated with PIO (10 mg/kg, intraperitoneal) or AZM (160 mg/kg, oral). We observed a sex-specific effect of PIO with significant antihyperalgesic effects in females, but not males. In contrast, AZM was effective in both sexes. Our data support the use of PIO and AZM as novel therapies for SCI pain and highlight the importance of considering sex as a biological variable in clinical and experimental SCI pain research.

Original languageEnglish
Pages (from-to)2372-2376
Number of pages5
JournalJournal of Neurotrauma
Volume36
Issue number15
DOIs
StatePublished - Aug 1 2019

Bibliographical note

Funding Information:
This work is supported by NIH NINDS R01NS091582.

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

Keywords

  • PPAR
  • macrophage
  • microglia
  • sex
  • thiazolidinedione

ASJC Scopus subject areas

  • Clinical Neurology

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