HMOX1 and Hyperglycemia: Moreover, given that oxidative stress induced by hyperglycemia is a key factor for the progress of diabetic neuropathy and that HO-1 triggered by the transcription factor Nrf2 potentiated the effects of delta-opioid receptors (DOR) in type 2 diabetic mice [20], we hypothesized that pre-treatment with CoPP or sulforaphane (SFN), a Nrf2 transcription factor activator, might increase the analgesic efficacy produced by selective CB2R agonists in animals with type 2 diabetes.