Figure 1

APAP elicits TRPA1-dependent hypothermia.

(A) Subcutaneous injections of APAP evoked a dose-dependent hypothermia in C57BL/6J mice (n = 6–12). (B) APAP (300 mg/kg) reduced the body temperature in Trpa1^+/+ mice but was without effect in Trpa1^−/− mice (n = 6–11, see panel C for key to the symbols). (C) Intrathecal administration of APAP (100μg) did not reduce body temperature (n = 6). (D) Resiniferatoxin (RTX, 6.3 μg/kg, s.c.) induced a profound hypothermia in Trpa1^+/+ and Trpa1^−/− mice (n = 6). (E) APAP (300 mg/kg s.c.) evoked hypothermia in non-RTX treated Trpa1^+/+ mice, but was without effect in Trpa1^−/− and RTX treated Trpa1^+/+ mice (n = 6). (F) Indomethacin (10 mg/kg, s.c.) did not alter body temperature and did not inhibit APAP (300mg/kg) evoked hypothermia (n = 6). (G) Oral administration of the TRPA1 antagonist CHEM5861528 (40–300 mg/kg, 45 min before APAP) produced a dose-dependent inhibition of APAP evoked hypothermia (n = 6). (H) Intraperitoneal injections of the TRPA1 agonist cinnamaldehyde (CA, 125 mg/kg) induced a marked hypothermia in Trpa1^+/+ mice, which was significantly reduced in Trpa1^−/− mice (n = 6). Data are mean ± sem; ^*p < 0.05, ^**p < 0.01, ^***p < 0.001 compared to vehicle and ^†p < 0.05, ^††p < 0.01, ^†††p < 0.001 compared to Trpa1^+/+.