Fig. 2. The effect of pretreatment with gabexate or ENMD-1068 on mechanical hyperalgesia after plantar surgery in mice. Time-response curve of the pre-administration of gabexate (1 nmol/paw, intraplantar [i.pl.]) (A ) or ENMD-1068 (100 nmol/paw, i.pl.) (C ) and the dose-response curve of the preadministration of gabexate (0.01–1 nmol/paw, i.pl.) (B ) or ENMD-1068 (10–100 nmol/paw, i.pl.) (D ) on mechanical hyperalgesia at 0.5 and 1 h, respectively, after plantar surgery in mice. The vertical bars  represent the means + SEM (A , n= 6 to phosphate buffered saline [PBS] and n = 5 to gabexate groups; B , n = 6 to PBS, basal, and gabexate 0.1 nmol/paw groups and n = 5 to gabexate 0.01 and 1 nmol/paw groups; C , n = 6 to PBS and ENMD-1068 groups; D , n = 7 to PBS, basal, and ENMD-1068 100 nmol/paw groups and n = 6 to ENMD-1068 10 and 30 nmol/paw groups). #P < 0.01 when compared to baseline (B ); one-way ANOVA followed by Dunnett test. **P < 0.01 when compared to the PBS-treated group; one-way ANOVA followed by Dunnett test (B , D ). *P < 0.05, **P < 0.01, ***P < 0.001 when compared to the PBS-treated group; two-way ANOVA followed by Bonferroni correction test (A , C ).

Fig. 2. The effect of pretreatment with gabexate or ENMD-1068 on mechanical hyperalgesia after plantar surgery in mice. Time-response curve of the pre-administration of gabexate (1 nmol/paw, intraplantar [i.pl.]) (A ) or ENMD-1068 (100 nmol/paw, i.pl.) (C ) and the dose-response curve of the preadministration of gabexate (0.01–1 nmol/paw, i.pl.) (B ) or ENMD-1068 (10–100 nmol/paw, i.pl.) (D ) on mechanical hyperalgesia at 0.5 and 1 h, respectively, after plantar surgery in mice. The vertical bars  represent the means + SEM (A , n= 6 to phosphate buffered saline [PBS] and n = 5 to gabexate groups; B , n = 6 to PBS, basal, and gabexate 0.1 nmol/paw groups and n = 5 to gabexate 0.01 and 1 nmol/paw groups; C , n = 6 to PBS and ENMD-1068 groups; D , n = 7 to PBS, basal, and ENMD-1068 100 nmol/paw groups and n = 6 to ENMD-1068 10 and 30 nmol/paw groups). #P < 0.01 when compared to baseline (B ); one-way ANOVA followed by Dunnett test. **P < 0.01 when compared to the PBS-treated group; one-way ANOVA followed by Dunnett test (B , D ). *P < 0.05, **P < 0.01, ***P < 0.001 when compared to the PBS-treated group; two-way ANOVA followed by Bonferroni correction test (A , C ).

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