Figure 5.
Vaso-occlusion and mechanical hyperalgesia induced by cold exposure are inhibited by anti-P-selectin mAb. (A) Anti–P-selectin mAb inhibited cold-induced vaso-occlusion in HbSS mice. Townes HbSS mice (n = 4 per group) were implanted with DSFC windows. After baseline selection of flowing subcutaneous venules, mice were injected IV via the tail vein with isotype control or anti–P-selectin mAb (1.2 mg/kg). Thirty minutes later, mice were exposed to cold at 10°C (50°F) for 1 hour and returned to RT. Microvascular stasis was measured in the same venules at the indicated times after cold exposure. Values are means ± SEM. ∗∗P < .01 and ∗∗∗P < .001, anti–P-selectin mAb vs control mAb (2-way ANOVA with the Sidak multiple comparison test). (B) Anti–P-selectin mAb inhibited cold-induced mechanical hyperalgesia in Townes HbSS mice. Baseline mechanical threshold was measured in the hind paws of HbSS mice (n = 4 mice per group) using von Frey filaments. After baseline pain measurements, nonhyperalgesic mice were injected IV via the tail vein with isotype control or anti–P-selectin mAb (1.2 mg/kg). Thirty minutes after mAb infusion, mice were exposed to cold at 10°C (50°F) for 1 hour and then returned to RT, and mechanical threshold was measured at the indicated times after cold exposure. (C) Anti–P-selectin mAb did not inhibit mechanical hyperalgesia in a complete Freund's adjuvant (CFA) pain model in nonsickle C57BL6 mice. Baseline mechanical threshold was measured in the hind paws of C57BL6 mice (n = 4 mice per group) using von Frey filaments. After baseline measurements, mice received a single injection of 10 μL of CFA into the middle of the plantar surface of 1 hind paw. Twenty-four hours after CFA injection, mice were injected IV via the tail vein with isotype control or anti–P-selectin mAb (1.2 mg/kg). Mechanical threshold was determined at the indicated times after mAb infusion. (B-C) Values are means ± SEM. ∗P < .05, anti–P-selectin mAb vs control mAb (2-way ANOVA with the Tukey multiple comparison test). #P < .05 and ##P < .01, vs baseline (2-way ANOVA, with the Dunnett multiple comparison test).

Vaso-occlusion and mechanical hyperalgesia induced by cold exposure are inhibited by anti-P-selectin mAb. (A) Anti–P-selectin mAb inhibited cold-induced vaso-occlusion in HbSS mice. Townes HbSS mice (n = 4 per group) were implanted with DSFC windows. After baseline selection of flowing subcutaneous venules, mice were injected IV via the tail vein with isotype control or anti–P-selectin mAb (1.2 mg/kg). Thirty minutes later, mice were exposed to cold at 10°C (50°F) for 1 hour and returned to RT. Microvascular stasis was measured in the same venules at the indicated times after cold exposure. Values are means ± SEM. ∗∗P < .01 and ∗∗∗P < .001, anti–P-selectin mAb vs control mAb (2-way ANOVA with the Sidak multiple comparison test). (B) Anti–P-selectin mAb inhibited cold-induced mechanical hyperalgesia in Townes HbSS mice. Baseline mechanical threshold was measured in the hind paws of HbSS mice (n = 4 mice per group) using von Frey filaments. After baseline pain measurements, nonhyperalgesic mice were injected IV via the tail vein with isotype control or anti–P-selectin mAb (1.2 mg/kg). Thirty minutes after mAb infusion, mice were exposed to cold at 10°C (50°F) for 1 hour and then returned to RT, and mechanical threshold was measured at the indicated times after cold exposure. (C) Anti–P-selectin mAb did not inhibit mechanical hyperalgesia in a complete Freund's adjuvant (CFA) pain model in nonsickle C57BL6 mice. Baseline mechanical threshold was measured in the hind paws of C57BL6 mice (n = 4 mice per group) using von Frey filaments. After baseline measurements, mice received a single injection of 10 μL of CFA into the middle of the plantar surface of 1 hind paw. Twenty-four hours after CFA injection, mice were injected IV via the tail vein with isotype control or anti–P-selectin mAb (1.2 mg/kg). Mechanical threshold was determined at the indicated times after mAb infusion. (B-C) Values are means ± SEM. ∗P < .05, anti–P-selectin mAb vs control mAb (2-way ANOVA with the Tukey multiple comparison test). #P < .05 and ##P < .01, vs baseline (2-way ANOVA, with the Dunnett multiple comparison test).

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