The conundrum and enigma of painful and painless neuropathy

The natural history and pathophysiology of diabetic painful and painless neuropathy remain an enigma to most clinicians, researchers, and persons with diabetes. The condition is clinically very well observed and described hundreds of years ago already, but a lack of robust clinical endpoints and methodologies continues to hamper diagnostics, therapeutics, and research investigations. Adding to this, signs and symptoms may differ widely from one person to another, seemingly associated with gender, age, type of diabetes, and other complications of diabetes. Some suffer only sensory loss, while others also experience uncomfortable, at times excruciating pain, and some go completely free in spite of many years of diabetes. Currently recommendations and conventional screening programs hamper the implementation of timely preventative measures in the individual person with diabetes and allows progression of complications. There is a clear need for robust and validated test methods and clinical endpoints to detect painful and painless peripheral neuropathy separately before it becomes clinically significant, and more so to target and focus on small fiber neuropathy as the location of earliest detectable neuropathy impairment. Theoretically, this could be a key to better compare and understand the associations, causative, or reflective, between painful and painless neuropathies. But, most of all it could prove to be invaluable for early detection and prevention of peripheral neuropathy. Recently, however, novel technologies have shone some light on possible associations between painful and painless diabetic neuropathy offering a new understanding of these joint conditions. This is hypothesis generating and gives hope for coming clinical studies aimed at early detection, prevention, and description of pathophysiological mechanisms, not only for painful and painless diabetic peripheral neuropathy, but also for diabetic neuropathy in general.