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
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.