Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain

Figure 1 Effects of melatonin and melatonergic agonists on mustard oil-induced pain. A: Ip melatonin, Neu-P11, and Neu-P12 (all 25 and 50 mg/kg) reduced the number of pain-related behaviors in the mustard oil (MO) sensitivity test 15 min after drug administration; B: Oral melatonin, Neu-P11 and Neu-P12 (all 25 mg/kg, 50 mg/kg and 100 mg/kg) decreased the number of pain-related behaviors in the MO sensitivity test 20 min after drug administration; C: Effect of ip injected melatonin, Neu-P11 and Neu-P12 (all at 50 mg/kg) on the number of pain-related behaviors in the MO sensitivity test at 15 min, 2 and 4 h after drug administration. Data are mean ± SE (n = 6-10). ^bP < 0.01 vs MO; ^cP < 0.05, ^dP < 0.01 vs vehicle + MO; ^eP < 0.05, ^fP < 0.01 vs drug; ^gP < 0.05, ^hP < 0.01 vs control.

Figure 2 Effect of naloxone and melatonergic antagonists on melatonin, Neu-P11 and Neu-P12-induced effects on mustard oil-induced pain. A: Effects of antagonists: ip naloxone (1 mg/kg), but not luzindole (5 mg/kg) or 4-P-PDOT (4 mg/kg) blocked the effects of melatonin, Neu-P11, and Neu-P12 (all at 25 mg/kg, ip) on the number of pain-related behaviors in the mustard oil sensitivity test 15 min after drug administration; B: Icv naloxone (5 μg/animal), luzindole (5 μg/animal) and 4-P-PDOT (10 μg/animal) blocked the effects of melatonin, Neu-P11 and Neu-P12 (all at 25 mg/kg, ip) in the mustard oil sensitivity test 15 min after drug administration. Data are mean ± SE (n = 6-10). ^aP < 0.05, ^bP < 0.01 vs control; ^cP < 0.05 vs drugs + vehicle; ^eP < 0.05, ^fP < 0.01 vs vehicle icv + drugs ip.

Figure 3 Melatonin, Neu-P11 and Neu-P12 decreased the number of pain-related behaviors. A: Melatonin, Neu-P11 and Neu-P12 (all at 25 mg/kg, ip) decreased the number of pain-related behaviors in the capsaicin-induced visceral pain test 15 min after drug administration; B: Melatonin, Neu-P11 and Neu-P12 (all 5 at mg/kg, ip) decreased the number of pain-related behaviors in the writhing test 15 min after drug administration. Data are mean ± SE (n = 6-10). ^aP < 0.05, ^bP < 0.01 vs control.