The role of spinal delta sub(1)-opioid receptors in inhibiting the formalin-induced nociceptive response in diabetic mice

• Published in: European journal of pharmacology Vol. 326; no. 1; pp. 31 - 36
• Main Authors: Kamei, J, Kashiwazaki, T, Hitosugi, H, Nagase, H
• Format: Journal Article
• Language: English
• Published: 01.05.1997
• ISSN: 0014-2999

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 delta sub(1)-opioid receptors in inhibiting the formalin-induced nociceptive response in diabetic mice, we assessed the effect of 7-benzylidenenaltrexone, a selective delta sub(1)-opioid receptor antagonist, and naltriben, a selective delta sub(2)-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 mu g/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 mu g/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 delta sub(1)-opioid receptor-mediated endogenous antinociceptive system may inhibit the formalin-induced second phase of the nociceptive response in diabetic mice.