Reduced thermal hypersensitivity in S1P₁^−/−mice.

<p>(A) Injection of the S1P₁ agonist SEW2871 induced a significant transient decrease in paw withdrawal latencies in S1P₁^fl/fl (n = 9) which was significantly less pronounced than in SNS-S1P₁^−/− mice (n = 10, *p<0.05; ANOVA). (B, C) While only a minor reduction of paw withdrawal latencies was observed in both mouse strains with local low dose S1P injection, we observed a significant decrease in paw withdrawal latencies in S1P₁^fl/fl mice (n = 7) which was similar to wt. In SNS-S1P₁^−/− mice the degree of hypersensitivity was significantly ameliorated in comparison to S1P₁^fl/fl mice (n = 9, *p<0.05, ** p<0.01; ANOVA). (D) CFA (20 µl) injection into the plantar hindpaw induced a pronounced decrease of PWL which was significantly attenuated in S1P₁-Cre mice (p<0.05, n = 4; ANOVA). (E) Paw swelling was similar in SNS-S1P₁^−/− and S1P₁^fl/fl mice (n = 4).