Hyperalgesia is one of the symptoms of diabetic neuropathy, particularly in the early stages of diabetic neuropathy. The activation of neurokinin1 (NK1) receptors in the spinal cord by substance P results in thermal and mechanical hyperalgesia. The relationship between glucose and NK1 receptor expression has not been reported. We investigated the hypothesis that in the diabetic state, high glucose directly induce NK1 receptor expression in rat spinal neuronal cells. We used primary cultures of neonatal rat spinal neurons to elucidate whether NK1 receptor expression is regulated by glucose. NK1 receptor expression increased in cells cultured under a high glucose condition. Although inhibitors of protein kinase A, protein kinase C, and aldose reductase did not affect NK1 receptor expression, α-lipoic acid suppressed it under high glucose conditions. A specific inhibitor of mitochondrial complex II also suppressed the increase in NK1 receptor expression. These results indicate that high glucose increases NK1 receptor expression, which is due to oxidative stress and NK1 receptor expression contributes to mechanisms underlying hyperalgesia in diabetic neuropathy.
