Decreased opioid-induced antinociception but unaltered G-protein activation in the genetic-diabetic NOD mouse

• Published in: European journal of pharmacology 2000-08, Vol.401 (3), p.375-379
• Main Authors: Pieper, Galen M, Mizoguchi, Hirokazu, Ohsawa, Masahiro, Kamei, Junzo, Nagase, Hiroshi, Tseng, Leon F
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - pharmacology; Animals; Antinociception; Associated diseases and complications; Benzamides - pharmacology; Binding, Competitive - drug effects; Biological and medical sciences; Diabetes mellitus; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enkephalin, Ala-MePhe-Gly- - pharmacology; Female; G-protein; GTP-Binding Proteins - drug effects; GTP-Binding Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Injections, Intraventricular; Medical sciences; Medulla Oblongata - drug effects; Medulla Oblongata - metabolism; Membranes - drug effects; Membranes - metabolism; Mice; Mice, Inbred NOD; Nociceptors - drug effects; Oligopeptides - pharmacology; Opioid; Pain - prevention & control; Piperazines - pharmacology; Pons - drug effects; Pons - metabolism; Receptors, Opioid - agonists; Receptors, Opioid - metabolism; Sulfur Radioisotopes; δ-Opioid receptor; μ-Opioid receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00459-3

Previous evaluation of antinociceptive action in experimental diabetes has been conducted almost exclusively in chemically induced diabetes mellitus. The purpose of the present study was to evaluate antinociceptive response and G-protein activation by μ-opioid receptor and δ-opioid receptor agonists in the genetic non-obese diabetic (NOD) mouse, a model of type I insulin-dependent diabetes mellitus (IDDM). Tail-flick latency before and after hyperglycemia was unaltered. Hyperglycemic NOD mice were hyporesponsive to intracerebroventricular (i.c.v.) injections of [ d-Ala 2]deltorphin II but not to [ d-Ala 2, N-MePhe 4, Gly-ol 5]enkephalin (DAMGO); however, G-protein activation in pons/medulla assessed by [ 35S]GTPγS binding was not diminished. This suggests that a G-protein defect in signaling cannot account for the hyporesponsiveness of antinociception in this genetic model of IDDM.