Blockade of either Notch1 or TLR4 signaling pathway produced anti-nociceptive effects and inhibited the expression of TLR4 mRNA and protein, Notch1 mRNA, NICD1 protein, which suggests that they may be putative interactions when the pain of diabetic neuropathy is developed and may be the target for future pharmacological pain relief tools. Here, NOTCH1 is linked to diabetic neuropathy.