Melatonin reduces formalin-induced nociception and tactile allodynia in diabetic rats.
The purpose of this study was to assess the antinociceptive and antiallodynic effect of melatonin as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral administration of melatonin (10-300 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. In addition, K-185 (a melatonin MT(2) receptor antagonist, 0.2-2 mg/kg, s.c.) completely blocked the melatonin-induced antinociception in diabetic rats, whereas that naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) and naltrindole (a selective delta opioid receptor antagonist, 0.5 mg/kg, s.c.), but not 5'-guanidinonaltrindole (a selective kappa opioid receptor antagonist, 1 mg/kg, s.c.), partially reduced the antinociceptive effect of melatonin. Given alone K-185, naltrexone, naltrindole or 5'-guanidinonaltrindole did not modify formalin-induced nociception in diabetic rats. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of melatonin (75-300 mg/kg) dose-dependently reduced tactile allodynia in diabetic rats. Both antinociceptive and antiallodynic effects were not related to motor changes as melatonin did not modify number of falls in the rotarod test. Results indicate that melatonin is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that melatonin MT(2) and delta opioid receptors may play an important role in these effects.
Arreola-Espino
Rosaura
R
Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
Urquiza-Marín
Héctor
H
Ambriz-Tututi
Mónica
M
Araiza-Saldaña
Claudia Ivonne
CI
Caram-Salas
Nadia L
NL
Rocha-González
Héctor I
HI
Mixcoatl-Zecuatl
Teresa
T
Granados-Soto
Vinicio
V
D000700:Analgesics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D005260:Female; D005557:Formaldehyde; D006146:Guanidines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors
C503316:6'-guanidinonaltrindole; D000700:Analgesics; D006146:Guanidines; D007211:Indoles; C121418:K 185; D009292:Narcotic Antagonists; D044123:Receptor, Melatonin, MT2; D005557:Formaldehyde; D009271:Naltrexone; D008550:Melatonin