The impact of endogenous N/OFQ on DPN: Insights into lower limb blood flow regulation in rats

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, often accompanied by impaired vascular endothelial function in the lower limbs. This dysfunction is characterized by a reduced vasodilatory response, leading to decreased blood flow in the lower limbs and ultimately contributing to the development of diabetic peripheral neuropathy. To delve deeper into this pathological process, the study employed bioinformatics to identify and analyze genes highly active in DPN. The investigation revealed that Membrane metalloendopeptidase (MME) was effectively mitigated by its antagonist. Male Sprague-Dawley (SD) rats served as the model to systematically explore the intrinsic connection among the nociceptible/orphanin FQ-N/OFQ receptor (N/OFQ-NOP) system, femoral artery blood flow in the lower extremities, MME, and DPN. The rats were randomized into two groups: a control group and a DPN group induced by a single intraperitoneal injection of 55 mg/kg streptozotocin (STZ), with 6 rats in each group. The findings indicated that compared to the control group, the DPN group exhibited a significant reduction in femoral artery blood flow. This was accompanied by a notable increase in serum N/OFQ concentration, heightened expression of opioid-related nociceptive protein receptor 1 (OPRL1) and MME in femoral artery tissues of the lower limbs, and an elevated sciatic nerve stimulation threshold. These results suggest that the serum N/OFQ level in DPN rats is increased, which may promote the occurrence of peripheral neuropathy by up regulating MME and reducing peripheral flow distribution.