Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia

被引:31
作者
Lei, Jianxun [1 ]
Benson, Barbara [1 ]
Tran, Huy [1 ]
Ofori-Acquah, Solomon F. [2 ,3 ]
Gupta, Kalpna [1 ]
机构
[1] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Vasc Biol Ctr, Box 736 UMHC, Minneapolis, MN 55455 USA
[2] Univ Pittsburgh, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA
[3] Univ Pittsburgh, Vasc Med Inst, Ctr Translat & Int Hematol, Pittsburgh, PA USA
来源
PLOS ONE | 2016年 / 11卷 / 08期
基金
美国国家卫生研究院;
关键词
ACUTE CHEST SYNDROME; REPERFUSION INJURY; NEUROPATHIC PAIN; MICE; DISEASE; CHILDREN; ACTIVATION; AGE; HEMOGLOBIN; SEX;
D O I
10.1371/journal.pone.0160608
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 alpha and beta transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain.
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页数:18
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