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.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health (NIH)UO1 HL117664 and RO1 103773 and University of Minnesota, Institute for Engineering in Medicine (iem.umn.edu) grants to KG and NIH UO1HL117721 and RO1 HL106192 to SOA. The authors would like to thank Ritu Jha and Susan Thompson for breeding, genotyping, and phenotyping mice; and Michael J Franklin for editorial assistance.