Figure 8. Topical supply of cholesterol alleviates subacute and chronic arthritis pain.

1. Mechanical sensitivity of mice injected with 2% carrageenan (Carra; n = 13; blue line) or co‐injected with carrageenan and 5.6 mM of cholesterol (Carra + chol 5.6 mM; n = 12; green). Ibuprofen (75 mg/kg) was injected intraperitoneally 1 h prior to intraplantar injection of carrageenan into the hind paw (Carra + ibu; n = 15; gray line).
2. Cholesterol content of ipsilateral and contralateral skin biopsies of mice intraplantarly injected with 3% carrageenan and treated for 1.5 h with either a topical application of an HEC gel containing 5.6 mM of cholesterol (n = 9) or a blank gel containing no cholesterol (0 mM; n = 8).
3. Mechanical sensitivity of mice injected with 2% carrageenan and treated with topical application of HEC gels containing 0 mM (blue, n = 12) or 5.6 mM (green, n = 10) of cholesterol. Saline‐injected animals were treated with the blank gel (0 mM cholesterol, black, n = 4).
4. Mechanical sensitivity of CFA‐induced arthritic mice. Hyperalgesic mice received topical HEC gels containing no cholesterol (blue, n = 6) or containing 5.6 mM of cholesterol (light green, n = 7) or 28 mM of cholesterol (dark green, n = 7) or containing 5% ibuprofen (gray, n = 6). Saline‐injected animals (black, n = 4), treated with the blank gel (0 mM cholesterol), were also included to ensure that anesthesia does not alter normal mechanical perception of mice. Right inset: 7 days after ipsilateral injections of CFA, mice exhibited severe swelling of the ankle compared with saline‐injected animals.

Data information: All values are shown as mean ± standard error of the mean (SEM). In behavioral studies (A, C, and D), * symbols refer to statistical significance with 0 mM chol curve. Cholesterol quantification (B) was analyzed with a Mann–Whitney U‐test. Behavioral data were analyzed with two‐way ANOVA and Bonferroni post‐tests. ***P < 0.001, **P < 0.01, and *P < 0.05.