The role of spinal delta1-opioid receptors in inhibiting the formalin-induced nociceptive response in diabetic mice.
Injection of formalin into the hindpaw of mice produced a biphasic nociceptive response consisting of immediate (first-phase) and tonic (second-phase) components. In diabetic mice, the flinching response of the first phase was increased while that in the second phase was decreased in diabetic mice relative to the results in non-diabetic mice. To examine the role of supraspinal and/or spinal endogenous delta1-opioid receptors in inhibiting the formalin-induced nociceptive response in diabetic mice, we assessed the effect of 7-benzylidenenaltrexone, a selective delta1-opioid receptor antagonist, and naltriben, a selective delta2-opioid receptor antagonist, administered either i.c.v. or i.t., on the formalin-induced flinching response. The second-phase response appeared when diabetic mice were pretreated with 7-benzylidenenaltrexone (0.1 and 0.3 mg/kg, s.c.), but not with naltriben (0.3 and 1 mg/kg, s.c.). On the other hand, while 7-benzylidenenaltrexone (0.1, 0.3 and 1 microg/mouse) administered i.t. had no significant effect on the first phase, it significantly and dose-dependently increased the second phase of the formalin-induced flinching response in diabetic mice. 7-Benzylidenenaltrexone (1 and 3 microg/mouse) administered i.c.v. had no significant effect on either the first- or the second-phase response in both non-diabetic and diabetic mice. These results suggest that a spinal delta1-opioid receptor-mediated endogenous antinociceptive system may inhibit the formalin-induced second phase of the nociceptive response in diabetic mice.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa-ku, Tokyo, Japan. kamei@hoshi.ac.jp
Kashiwazaki
T
T
Hitosugi
H
H
Nagase
H
H
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001597:Benzylidene Compounds / Q000008:administration & dosage / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D001597:Benzylidene Compounds; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C077358:7-benzylidenenaltrexone; D005557:Formaldehyde; D009271:Naltrexone