Effect of diabetes on bradykinin-induced thermal hyperalgesia in mice

• Published in: European journal of pharmacology Vol. 390; no. 1; pp. 113 - 118
• Main Authors: Kamei, Junzo, Ohsawa, Masahiro, Hitosugi, Hideki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.02.2000; Elsevier
• Subjects: Analgesics; Animals; Biological and medical sciences; Bradykinin; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Calphostin C; Diabetes; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Activators - pharmacology; Enzyme Inhibitors - pharmacology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Hot Temperature; Hyperalgesia - chemically induced; Hyperalgesia - physiopathology; Injections, Spinal; Male; Medical sciences; Mice; Mice, Inbred ICR; Mouse; Naphthalenes - pharmacology; Neuropharmacology; Pharmacology. Drug treatments; Phorbol 12,13-Dibutyrate - pharmacology; Phorbol-12, 13-dibutyrate; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Reaction Time - drug effects; Thermal hyperalgesia; Protein kinase C; Calphostin C; Mouse; Bradykinin; Phorbol-12, 13-dibutyrate; Diabetes; Thermal hyperalgesia; Endocrinopathy; Spinal cord; Enzyme; Transferases; Diabetes mellitus; Rodentia; Cytokine; Central nervous system; Normal; Intrathecal administration; Hyperalgesia; Vertebrata; Regulation(control); Mammalia; Analgesic; Animal; Mechanism of action
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00917-6

To investigate the role of protein kinase C in the attenuation of bradykinin-induced thermal hyperalgesia in diabetic mice, we examined the effects of a protein kinase C activator or inhibitor on the i.t. bradykinin-induced hyperalgesia in diabetic and non-diabetic mice. Intrathecal injection of bradykinin caused a transient antinociceptive effect, which diminished within 30 min, and then produced a thermal hyperalgesia, which lasted about 120 min, in non-diabetic mice. Although the duration of the antinociceptive phase was longer in diabetic mice than in non-diabetic mice, the hyperalgesic response was not observed in diabetic mice. The bradykinin-induced hyperalgesia was dose-dependently and significantly enhanced by pretreatment with calphostin C (0.3 to 3 pmol, i.t.), a specific protein kinase C inhibitor, in diabetic mice. However, calphostin C (3 pmol, i.t.) had no significant effect on bradykinin-induced hyperalgesia in non-diabetic mice. On the other hand, pretreatment with phorbol-12, 13-dibutyrate (12.5 to 50 pmol, i.t.), a protein kinase C activator, significantly and dose-dependently reduced bradykinin-induced hyperalgesia in non-diabetic mice. However, phorbol-12, 13-dibutyrate (50 pmol, i.t.) had no significant effect on bradykinin-induced hyperalgesia in diabetic mice. These results suggest that the change in bradykinin-induced thermal hyperalgesia in diabetic mice may be due, at least in part, to the modification of nociceptive transmission in the spinal cord by the activation of protein kinase C.