Orofacial sensory changes after streptozotocin-induced diabetes in rats

Peripheral neuropathy is a common complication of diabetes and is often accompanied by episodes of pain. There is evidence that diabetic neuropathy may affect the trigeminal nerve, altering the transmission of orofacial sensory information. Structural changes in the trigeminal ganglia may be involved in the development of these sensory alterations. Herein, we evaluate the development of orofacial sensory changes after streptozotocin-induced diabetes in rats, and their sensitivity to pregabalin and morphine treatments. Furthermore, stereological analysis of the trigeminal ganglia was performed. Diabetic rats showed similar responses to 1% formalin applied into the upper lip compared to normoglycemic rats on weeks 1, 2 and 4 after streptozotocin. Additionally, there was no difference in the facial mechanical threshold of normoglycemic and diabetic rats, on weeks 1 up to 5 after streptozotocin, while the paw mechanical threshold of diabetic rats was significantly reduced. In contrast, diabetic rats developed long-lasting orofacial heat and cold hyperalgesia. Moreover, stereological analyses revealed significant neuronal loss in the trigeminal ganglia of diabetic compared to normoglycemic rats. Pregabalin treatment (30 mg/kg, p.o.) of diabetic rats resulted in marked and prolonged (up to 6 h) reduction of heat and cold orofacial hyperalgesia. Likewise, morphine treatment (2.5 mg/kg, s.c.) abolished orofacial heat and cold hyperalgesia, but its effect was significant only up to 1 h after the administration. In conclusion, the results of the present study demonstrated that streptozotocin-treated rats developed long-lasting orofacial heat and cold hyperalgesia, which is more amenable to reduction by pregabalin than morphine.

► Diabetic rats showed similar responses of control rats to orofacial formalin.
► Diabetic rats did not develop orofacial mechanical hyperalgesia.
► STZ-induced diabetes led to the development of orofacial thermal hyperalgesia.
► Diabetic rats exhibited significant trigeminal neuronal loss.
► Pregabalin and morphine reduced orofacial thermal hyperalgesia in STZ-rats.