Abstract
Background: Painful Diabetic Neuropathy (PDN) is a devastating condition affecting one in three people with diabetes.
Introduction: Keeping in mind the unceasingly escalating prevalence of diabetes mellitus worldwide, the number of PDN patients is also expected to rise with a reduced quality of life in patients and a staggering increase in healthcare costs. Despite relentless efforts and continuous research, the commercially available medications for relieving diabetic neuropathy pain are only partially effective with substantial side effects. This is, in part, due to our partial awareness of the underlying complexities causing PDN. The pathogenesis of PDN remains elusive because of the difficulty in obtaining damaged nerve samples and the absence of non-invasive methods to investigate the pathogenesis at different stages of disease progression. The purpose of this review was to describe pathogenesis, clinical manifestations and treatment options for PDN. Methods: The keywords relevant to the scope of this paper were put in electronic databases (PubMed and Google Scholar) to fetch the relevant data. The data were then analyzed and compiled. Results: A simplified overview of PDN for researchers new to the field has been provided in an attempt to clarify common confusions. The changes in skin structure and functions in response to diabetes, diabetic neuropathy and painful diabetic neuropathy are also discussed. The unavailability of an efficacious pain reliever for PDN stresses on the need for identifying the microenvironmental factors that are altered in PDN and manipulate them to tailor targeted theranostics. Conclusion: In the end, we proposed to consider the altered skin structure, function and microenvironmental factors in the diabetic population for devising smart, targeted, stimuli-responsive treatment options to attain maximum pain relief with minimum side effects.Keywords: Pathogenesis of painful diabetic neuropathy, pDSPN, classification of painful diabetic neuropathy, cutaneous alterations in PDN, alterations in diabetic skin, diabetic neuropathy management, PDN management, localized drug delivery, diabetic foot.
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