1Spinal Cord and Brain Injury Research Center and Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky.
2Department of Anesthesia and Perioperative Medicine, the Pittsburgh Center for Pain Research, and the Opioid Research Center at the University of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
J Neurotrauma. 2019 Aug 1;36(15):2372-2376. doi: 10.1089/neu.2018.6207. Epub 2019 Feb 25.
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.
脊髓损伤（SCI）患者中有超过 75%会出现中枢神经性疼痛。越来越多的证据表明，性别是周围神经性疼痛发生和治疗中的一个重要生物学变量，但人们对性别在中枢神经性疼痛及其药物抑制中的作用知之甚少。为了验证在 SCI 疼痛中，性别会影响镇痛疗法的疗效这一假说，我们使用 SCI 疼痛的小鼠模型来确定吡格列酮（PIO）和阿奇霉素（AZM）的镇痛疗效。PIO 是一种经美国食品和药物管理局批准用于治疗糖尿病的药物，AZM 是一种具有免疫调节特性的常用大环内酯类抗生素。雄性和雌性小鼠接受 T9 挫伤性 SCI（75-kdyn）。损伤后 4 周，雄性和雌性小鼠均出现类似的热痛觉过敏，且这种过敏反应持续整个研究期间（14 周）。SCI 后 3 个月，用 PIO（10mg/kg，腹腔内注射）或 AZM（160mg/kg，口服）进行治疗。我们观察到 PIO 具有性别特异性，对雌性小鼠有显著的抗痛觉过敏作用，但对雄性小鼠没有作用。相比之下，AZM 对两种性别均有效。我们的数据支持将 PIO 和 AZM 作为治疗 SCI 疼痛的新疗法，并强调在 SCI 疼痛的临床和实验研究中，考虑性别作为生物学变量的重要性。
