Accumulation of sorbitol in the sciatic nerve modulates circadian properties of diabetes-induced neuropathic pain hypersensitivity in a diabetic mouse model.
The intensity of pain in diabetic neuropathy varies in a circadian time-dependent manner. It is well known that diabetes has two distinct types, which are differentiated based on the cause of the disease. Previous studies have yet to compare the circadian properties of the pain intensity of diabetic neuropathy between type I and type II diabetes. In this study, we demonstrated that the pain intensity of diabetic peripheral neuropathy in a db/db mouse model of type II diabetes showed a significant diurnal oscillation, but such time-dependent oscillation was not detected in a streptozotocin (STZ)-induced type I diabetic mouse model. The polyol pathway-induced accumulation of sorbitol in peripheral nerve cells suppresses Na+/K+-ATPase activity, which is associated with the intensity of pain in diabetic neuropathy. In db/db mice, this accumulation of sorbitol in peripheral nerve cells showed significant diurnal oscillation. In addition, pain intensity and Na+/K+-ATPase activity were decreased at the peak time of sorbitol accumulation in these mice. Although STZ-induced diabetic mice also showed sorbitol accumulation and Na+/K+-ATPase dysfunction, these measures did not oscillate in a time-dependent manner. These findings reveal differences in the circadian properties of pain hypersensitivity in mouse models of type I and type II diabetes, and also provide ideas for developing novel approaches to the management of diabetic neuropathy.
['Akamine|Takahiro|T|', 'Kusunose|Naoki|N|', 'Matsunaga|Naoya|N|', 'Koyanagi|Satoru|S|', 'Ohdo|Shigehiro|S|']
D000818:Animals D002940:Circadian Rhythm D003921:Diabetes Mellitus, Experimental D003922:Diabetes Mellitus, Type 1 D003924:Diabetes Mellitus, Type 2 D003929:Diabetic Neuropathies D004791:Enzyme Inhibitors D008297:Male D051379:Mice D008813:Mice, Inbred ICR D008817:Mice, Mutant Strains D009437:Neuralgia D012236:Rhodanine D012584:Sciatic Nerve D000254:Sodium-Potassium-Exchanging ATPase D013012:Sorbitol D053778:Thiazolidines
Sorbitol Neuropathic pain Diabetes Circadian rhythm Na(+)/K(+)-ATPase