Effects of cytidine 5'-diphosphocholine (CDP-choline) on the thermal nociceptive threshold in streptozotocin-induced diabetic mice.
Neuropathy accompanied by abnormal sensory perception is the most common complication in insulin-dependent and -independent diabetes mellitus. Since there are very few effective therapeutic regimens for sensory abnormalities in diabetes, we examined the effect of cytidine 5'-diphosphocholine (CDP)-choline on the thermal nociceptive threshold in streptozotocin-induced diabetic mice using the tail-flick test. Diabetic mice showed a shorter tail-flick latency at 1-4 weeks after streptozotocin treatment and a longer tail-flick latency after 8-12 weeks. This hyper- and hypoalgesia in diabetic mice was almost completely inhibited by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning on the day of streptozotocin treatment. Daily treatment with CDP-choline beginning 5 weeks after streptozotocin treatment attenuated the development of hypoalgesia. Diabetic mice showed a significant increase in Na(+)-K(+)-ATPase activity at 3 weeks after streptozotocin treatment, whereas Na(+)-K(+)-ATPase activity was decreased at 12 weeks after treatment. These alterations were normalized by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning the day of streptozotocin treatment. These results provide evidence to support the therapeutic potency of CDP-choline on the development of thermal hyper- and hypoalgesia and the progression of thermal hypoalgesia in diabetic mice. Moreover, these effects of CDP-choline may result from the normalization of Na(+)-K(+)-ATPase activity.
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp
Junzo
J
Kamei
Masahiro
M
Ohsawa
Shigeo
S
Miyata
Kazuki
K
Endo
Hiroyuki
H
Hayakawa
D000818:Animals; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000523:psychology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000523:psychology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000517:prevention & control / Q000523:psychology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018697:Nootropic Agents / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D012584:Sciatic Nerve / Q000187:drug effects / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline; D000254:Sodium-Potassium-Exchanging ATPase