Pharmacotherapy of Painful Diabetic Neuropathy: A Clinical Update

Abstract

The rising prevalence of diabetes mellitus (DM) leads on to an increase in chronic diabetic complications. Diabetic peripheral neuropathies (DPNs) are common chronic complications of diabetes. Distal symmetric polyneuropathy is the most prevalent form. Most patients with DPN will remain pain-free; however, painful DPN (PDPN) occurs in 6-34% of all DM patients and is associated with reduced health-related-quality-of-life and substantial economic burden. Symptomatic treatment of PDPN and diabetic autonomic neuropathy is the key treatment goals. Using certain patient related characteristics, subjects with PDPN can be stratified and assigned targeted therapies to produce better pain outcomes. The aim of this review is to discuss the various pathogenetic mechanisms of DPN with special reference to the mechanisms leading to PDPN and the various pharmacological and non-pharmacological therapies available for its management. Recommended pharmacological therapies include anticonvulsants, antidepressants, opioid analgesics, and topical medications.

Keywords: Diabetes mellitus; Diabetic peripheral neuropathy; Gabapentinoids; Opioids; Painful diabetic peripheral neuropathy.

Figure 1.

The pathophysiological mechanisms of PDPN and agents acting on the corresponding mechanisms. TRPV1: Transient receptor potential vanilloid 1, TRPM8: Transient receptor potential melastatin 8, P2X3: Purinoceptor 3, α2 A-R: α2-AdrenoReceptor, 5HT3-R: 5-Hydroxytryptamine receptor, SERT: Serotonin transporter, NET: Norepinephrine transporter, CGRP-R: Calcitonin gene-related peptide receptor, NK1-R: Neurokinin 1 receptor (NK1-R acts as receptor for substance P), NMDA-R: N-methyl-D-aspartate receptor, AMPA-R: α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (NAMDA-R and AMPA-R acts as receptor for glutamate), GABA A-R: Gamma aminobutyric acid A receptor, Glycine-R: Glycine receptor, TNF: Tumor necrosis factor, IL1-β: Interleukin 1 beta, Cytokine-R: Cytokine receptor (acts as receptor for TNF and IL1-β).