Contribution of Ca(2+) -dependent protein kinase C in the spinal cord to the development of mechanical allodynia in diabetic mice.
In this paper, we directly demonstrate, for the first time, the activation of Ca(2+)-dependent protein kinase C (PKC) in the spinal cord of diabetic mice. In streptozotocin (STZ)-treated (200 mg/kg, i.v.) diabetic mice, hypersensitivity (allodynia) to mechanical stimulation appeared 7 d after STZ injection. This mechanical allodynia was inhibited by intrathecal injection of the PKC inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and calphostin C, but not the protein kinase A inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89). The activity of membrane-associated Ca(2+)-dependent PKC in the spinal cords of STZ-induced diabetic mice was significantly higher than that observed in non-diabetic mice. These results suggest that activation of Ca(2+)-dependent PKC in the spinal cord, contributes to the mechanical allodynia in the pain associated with diabetic neuropathy.
Honda
Kenji
K
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. khonda@fukuoka-u.ac.jp
Koguchi
Masako
M
Koga
Kohei
K
Nakajima
Kyoko
K
Kobayashi
Fumito
F
Migita
Keisuke
K
Ogata
Shigenori
S
Hirabara
Yasutoshi
Y
Takano
Yukio
Y
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D006930:Hyperalgesia / Q000201:enzymology* / Q000209:etiology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011493:Protein Kinase C / Q000378:metabolism*; D013116:Spinal Cord / Q000201:enzymology*
D011493:Protein Kinase C; D002118:Calcium