fig2

Figure 2. The LFA-1 antagonist, BIRT377, similarly reverses allodynia in males and females. Mice were either sham or treated with perisciatic 5-0 suture. (A) All groups of mice show similar BL threshold hindpaw sensitivity. Following 5-0 CCI, all animals develop clear allodynia during an 8-day timecourse, showing stable allodynia on Day 10, with a main effect of time (ipsilateral: F_3.02,60.48 = 1003.02, P < 0.001; contralateral: F_3.56,71.15 = 528.60, P < 0.001). Additionally, a main effect of sex during the development of allodynia is observed (ipsilateral: F_1,20 = 21.27, P < 0.001; contralateral: F_1,20 = 13.06, P = 0.002), with a significant interaction between time and sex (ipsilateral: F_3.02,60.48 = 10.899, P < 0.001; contralateral: F_3.56,71.15 = 3.23, P = 0.021). Following injections on Day 10 post-surgery, clear reversal from allodynia resulting from BIRT377 injection is observed compared to vehicle treated mice, supported by a main effect of injection (ipsilateral: F_1,20 = 328.97, P < 0.001; contralateral: F_1,20 = 74.47, P < 0.001). In addition, male mice treated with BIRT377 appeared to reverse from allodynia 1 day sooner than female BIRT377-treated mice, as observed in hindpaw responses ipsilateral (F_1,20 = 12.12, P = 0.002) but not contralateral to the CCI, with an interaction between time and sex (ipsilateral: F_4.33,86.61 = 9.33, P < 0.001; contralateral: F_4.92,98.34 = 3.15, P = 0.012), and time and injection (ipsilateral: F_4.33,86.61 = 70.29, P < 0.001; contralateral: F_4.92,98.34 = 32.77, P < 0.001). (B) Experimental replication of BIRT377 reversal in males and females following CCI, with the onset and full development of bilateral allodynia occuring during a 10-day timecourse. Female mice reveal delayed onset of allodynia but no sex differences are observed by Day 10 post-surgery, when maximal allodynia is observed in both males and females. As previously observed, female 5-0 CCI mice treated with BIRT377 displayed slightly slower reversal from allodynia compared to males, with maximal bilateral reversal observed by Day 3 post-injection. n = 6 for all groups