An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US

Abstract

Neuropathic pain (NeuP) is a syndrome that results from damaged nerves and/or aberrant regeneration. Common etiologies of neuropathy include chronic illnesses and medication use. Chronic disorders, such as diabetes and alcoholism, can cause neuronal injury and consequently NeuP. Certain medications with antineoplastic effects also carry an exquisitely high risk for neuropathy. These culprits are a few of many that are fueling the NeuP epidemic, which currently affects 7%-10% of the population. It has been estimated that approximately 10% and 7% of US adults carry a diagnosis of diabetes and alcohol disorder, respectively. Despite its pervasiveness, many physicians are unfamiliar with adequate treatment of NeuP, partly due to the few reviews that are available that have integrated basic science and clinical practice. In light of the recent Centers for Disease Control and Prevention guidelines that advise against the routine use of μ-opioid receptor-selective opioids for chronic pain management, such a review is timely. Here, we provide a succinct overview of the etiology and treatment options of diabetic and alcohol- and drug-induced neuropathy, three different and prevalent neuropathies fusing the combined clinical and preclinical pharmacological expertise in NeuP of the authors. We discuss the anatomy of pain and pain transmission, with special attention to key ion channels, receptors, and neurotransmitters. An understanding of pain neurophysiology will lead to a better understanding of the rationale for the effectiveness of current treatment options, and may lead to better diagnostic tools to help distinguish types of neuropathy. We close with a discussion of ongoing research efforts to develop additional treatments for NeuP.

Keywords: alcohol use disorder; chemotherapy; diabetes mellitus; opioid receptors; pain; small-fiber neuropathy.

Figure 1

Overview of neuropathies affecting pain pathways. Notes: C and Aδ fibers are affected by diabetes, drugs, and alcohol (and its metabolite acetaldehyde), whereas large, myelinated Aα and Aβ fibers are affected by drugs and thiamine deficiency. Channels (sodium, calcium) and receptors (NMDA, serotonin, adrenergic, opioid) along the pain pathway serve as drug targets for treatment of chronic neuropathic pain. Abbreviations: NMDA, N-methyl-d-aspartate; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; TRP, transient receptor potential; CGRP, calcitonin gene-related peptide.