Abstract
Painful diabetic polyneuropathy (DPN) remains a significant persistent pain problem which detracts significantly from the quality of life of many patients. Multiple analgesics including antidepressants, antiepileptic drugs, opioids, topical local anesthetics, tramadol preparations, as well as other enteral, parenteral, and topical analgesics have been utilized to treat painful diabetic polyneuropathy with varying degrees of success. Insulin has been administered to some patients with painful DPN in efforts to achieve “tight glycemic control”–hoping to minimize the morbidity and mortality of various diabetic complications as well as improve symptoms of painful DPN. This article proposes that the administration of insulin and/or C-peptide and its signaling may contribute to relief from painful DPN–not wholly due to effects on glucose but in part due to their specific “inherent” effects on other processes including: oxidative stress, inflammation, apoptosis, and PARP function.