title: Treatment of painful diabetic neuropathy.
abstract: Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists.
authors.affiliation: Centre for Endocrinology and Diabetes, University of Manchester, Core Technology Facility (3rd floor), 46 Grafton Street, Manchester, M13 9NT, UK.
authors.forename: Saad
authors.initials: S
authors.lastname: Javed
authors.affiliation: School of Medicine, Institute of Human Development, Centre for Endocrinology and Diabetes, Manchester, UK.
authors.forename: Ioannis N
authors.initials: IN
authors.lastname: Petropoulos
authors.affiliation: School of Medicine, Institute of Human Development, Centre for Endocrinology and Diabetes, and Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Uazman
authors.initials: U
authors.lastname: Alam
authors.affiliation: School of Medicine, Institute of Human Development, Centre for Endocrinology and Diabetes, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, and Weill Cornell Medical College, Qatar.
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
keywords: diabetes mellitus; management; neuropathy