Painful and painless diabetic neuropathy: one disease or two?

Abstract Painful diabetic polyneuropathy (PDPN) is generally considered a variant of diabetic polyneuropathy (DPN) but the identification of distinctive aspects that characterize painful compared with painless DPN has however been addressed in many studies, mainly with the purpose of better understanding the mechanisms of neuropathic pain in the scenario of peripheral nerve damage of DPN, of determining risk markers for pain development, and also of recognizing who might respond to treatments. This review is aimed at examining available literature dealing with the issue of similarities and differences between painful and painless DPN in an attempt to respond to the question of whether painful and painless DPN are the same disease or not and to address the conundrum of why some people develop the insensate variety of DPN whilst others experience distressing pain. Thus, from the perspective of comparing painful with painless forms of DPN, this review considers the clinical correlates of PDPN, its distinctive framework of symptoms, signs, and nerve functional and structural abnormalities, the question of large and small fiber involvement, the peripheral pain mechanisms, the central processing of pain and some new insights into the pathogenesis of pain in peripheral polyneuropathies and PDPN.