Diabetes-induced peripheral neuropathic pain is characterized by hypersensitivity to innocuous stimuli, known as tactile allodynia. Pregabalin (PGN) is currently used to treat diabetes-induced peripheral neuropathy and allodynia. The present study demonstrated that the antiallodynic effect of PGN on diabetic mice was modulated by circadian changes in intestinal absorption. The intensity of tactile allodynia in streptozotocin-induced diabetic mice was alleviated by the oral administration of PGN. The antiallodynic effect of PGN was enhanced by its administration at the times of day when its intestinal absorption was accelerated. Organic cation transporter novel type-1 (Octn1) mediated the uptake of PGN into intestinal epithelial cells. The expression of Octn1 in the small intestine of diabetic mice oscillated in a circadian time-dependent manner. This oscillation in Octn1 appeared to cause the time-of-day–dependent changes in the intestinal absorption of PGN.
See article at J Pharmacol Exp Ther 2015, 354:65–72.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics