Painful and Painless Diabetic Neuropathies: What Is the Difference?

Abstract

Purpose of review: The prevalence of diabetes mellitus and its chronic complications are increasing to epidemic proportions. This will unfortunately result in massive increases in diabetic distal symmetrical polyneuropathy (DPN) and its troublesome sequelae, including disabling neuropathic pain (painful-DPN), which affects around 25% of patients with diabetes. Why these patients develop neuropathic pain, while others with a similar degree of neuropathy do not, is not clearly understood. This review will look at recent advances that may shed some light on the differences between painful and painless-DPN.

Recent findings: Gender, clinical pain phenotyping, serum biomarkers, brain imaging, genetics, and skin biopsy findings have been reported to differentiate painful- from painless-DPN. Painful-DPN seems to be associated with female gender and small fiber dysfunction. Moreover, recent brain imaging studies have found neuropathic pain signatures within the central nervous system; however, whether this is the cause or effect of the pain is yet to be determined. Further research is urgently required to develop our understanding of the pathogenesis of pain in DPN in order to develop new and effective mechanistic treatments for painful-DPN.

Keywords: Diabetes; Diabetic neuropathy; Neuropathic pain; Painful diabetic neuropathy; Peripheral neuropathy; Small fiber neuropathy.

Fig. 1

An overview of the current postulated pathogenesis of painful-DSPN. The risk factors for the generation of neuropathic pain in DSPN may include glycemic burden (duration of diabetes), obesity, female gender, and genetic variants of voltage-gated sodium channels (VGSC). Both the central and peripheral mechanisms have been postulated in the pathogenesis of painful-DSPN. ACC, anterior cingulate cortex. (Adapted from: Sloan G, et al. Diabetes Res Clin Pract. 2018; 144: 177–91, with permission from Elsevier) [17]