Metformin attenuates increase of synaptic number in the rat spinal dorsal horn with painful diabetic neuropathy induced by type 2 diabetes: a stereological study.

In our previous study, we have shown that number of synapses in the L5 segment of spinal dorsal horn increased significantly in a rat model of painful diabetic neuropathy (PDN) induced by high-dose of streptozotocin (an animal model of type 1 diabetes). The aims of this study were: (1) to determine whether high fat diet/low dose streptozotocin-diabetes, a rat model for type 2 diabetes, related PDN was also associated with this synaptic plasticity, (2) to reveal the range of this synaptic plasticity change occurred (in the whole length of spinal dorsal horn or only in the L5 lumbar segment of spinal dorsal horn) and (3) to discover whether treatment with metformin had effect on this synaptic plasticity. Male adult Sprague-Dawley rats were randomly allocated into the control group (n = 7), the PDN group (n = 6) and the PDN treated with metformin (PDN + M) group (n = 7), respectively. 28 days after medication, synaptic and neuronal numbers in the whole length of spinal dorsal horn or in 1 mm length of the L5 segment of spinal dorsal horn were estimated by the optical disector (a stereological technique). Compared to the control group and the PDN + M group, number of synapses in the L5 segment of spinal dorsal horn increased significantly in the PDN group (P < 0.05). There was no significant change between the control group and the PDN + M group in terms of the parameters in the L5 segment of the spinal dorsal horn (P > 0.05). Parameters of the whole length of spinal dorsal horn showed no significant changes (P > 0.05). Our results suggest that high fat diet/low dose streptozotocin diabetes related PDN is also associated with a numerical increase of synapses in the L5 segment of spinal dorsal horn but not in the whole length of spinal dorsal horn. Furthermore, the analgesic effect of metformin against PDN is related to its inhibition of numerical increase of synaptic number in the rat spinal dorsal horn.