Quantitative analysis revealed that the ZT2-ZT14 difference in nociceptive thresholds was amplified by 1.8-fold in shNRF2-treated db/db mice relative to AAV9-sc controls (p < 0.001), demonstrating that NRF2 knockdown potentiates diabetes-induced circadian disruption of pain sensitivity. The gene discussed is NFE2L2; the disease is diabetes mellitus.