Figure 3.

Blockade of microglial function elicits antinociceptive effects in disulfide HMGB1-subjected male but not female mice. Withdrawal threshold values after i.t. injection of disulfide HMGB1 (1 μg/mouse) or vehicle (saline) in (A) male and (B) female mice lacking TLR4 in microglia (LysM-TLR4^fl/fl) or TLR4^fl/fl (control mice). Withdrawal response before, and 6 and 24 hours after the first day i.t. injection of a combination of disulfide HMGB1 (1 μg/mouse) and minocycline (30 μg/mouse, microglial inhibitor) or disulfide HMGB1 (1 μg/mouse) and vehicle (PBS), as well as 6 hours after the second day intrathecal injection of minocycline (30 μg/mouse) or vehicle in (C) male and (D) female mice. Data are presented as mean ± SEM, n = 4 to 8 mice/group, *P < 0.05, **P < 0.01, ***P < 0.001 vs vehicle groups. ds HMGB1, disulfide high mobility group box 1 protein.