Lei Jianxun, Benson Barbara, Tran Huy, Ofori-Acquah Solomon F, Gupta Kalpna
Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2016 Aug 5;11(8):e0160608. doi: 10.1371/journal.pone.0160608. eCollection 2016.
Pain is a hallmark feature of sickle cell anemia (SCA) but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R) treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct "knock-in" strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain.
疼痛是镰状细胞贫血（SCA）的一个标志性特征，但慢性疼痛和急性疼痛的管理仍然是一项重大挑战。SCA的小鼠模型对于研究疼痛机制和开发新疗法至关重要。为推动这项工作，我们比较了人源化纯合BERK和汤姆斯镰状小鼠，以研究性别和年龄对疼痛行为的影响。与先前表征的BERK镰状小鼠相似，汤姆斯镰状小鼠随着年龄增长表现出更多的机械性、热性和深部组织痛觉过敏。与BERK小鼠和SCA患者的报道相似，雌性汤姆斯镰状小鼠比雄性表现出更多的痛觉过敏。在汤姆斯镰状小鼠中，缺氧/复氧（H/R）处理后，机械性、热性和深部组织痛觉过敏进一步增加。总之，这些数据表明，与性别和年龄匹配的汤姆斯镰状小鼠相比，BERK镰状小鼠在所有行为测量中表现出显著更高程度的痛觉过敏。然而，与BERK小鼠相比，汤姆斯小鼠中人类α和β转基因插入的基因不同的“敲入”策略，可能为进一步的基因操作以研究疼痛的特定机制提供相对优势。
