An Insight into Potential Pharmacotherapeutic Agents for Painful Diabetic Neuropathy.

Diabetes is the 4th most common disease affecting the world's population. It is accompanied by many complications that deteriorate the quality of life. Painful diabetic neuropathy (PDN) is one of the debilitating consequences of diabetes that effects one-third of diabetic patients. Unfortunately, there is no internationally recommended drug that directly hinders the pathological mechanisms that result in painful diabetic neuropathy. Clinical studies have shown that anticonvulsant and antidepressant therapies have proven fruitful in management of pain associated with PDN. Currently, the FDA approved medications for painful diabetic neuropathies include duloxetine, pregabalin, tapentadol extended release, and capsaicin (for foot PDN only). The FDA has also approved the use of spinal cord stimulation system for the treatment of diabetic neuropathy pain. The drugs recommended by other regulatory bodies include gabapentin, amitriptyline, dextromethorphan, tramadol, venlafaxine, sodium valproate, and 5 % lidocaine patch. These drugs are only partially effective and have adverse effects associated with their use. Treating painful symptoms in diabetic patient can be frustrating not only for the patients but also for health care workers, so additional clinical trials for novel and conventional treatments are required to devise more effective treatment for PDN with minimal side effects. This review gives an insight on the pathways involved in the pathogenesis of PDN and the potential pharmacotherapeutic agents. This will be followed by an overview on the FDA-approved drugs for PDN and commercially available topical analgesic and their effects on painful diabetic neuropathies.

Diabetic Neuropathy Pain Management: A Global Challenge.

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.