4.0 Review

Novel treatment modalities for painful diabetic neuropathy

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ELSEVIER SCI LTD
DOI: 10.1016/j.dsx.2021.01.004

Keywords

Diabetic peripheral neuropathy; Neuropathic pain; m-opioid receptor agonist-norepinephrinereuptake inhibitor (MONRI); Dual serotonin-noradrenergic reuptake inhibitor (SNRI); Purinergic receptors; Quality of life

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Novel pharmacological agents such as MONRI, SNRI, and cannabinoid receptor agonists have shown promise in alleviating neuropathic pain in human trials, targeting different aspects of pain pathways for therapeutic success. Further research and regulatory approvals are needed for these agents to be used clinically in managing painful diabetic neuropathy.
Background and aims: Painful diabetic neuropathy significantly affects the quality of life in people with diabetic peripheral neuropathy (DPN). Existing pharmacological agents have limited efficacy and development of tolerance is a limitation. Methods: The present review focuses on novel pharmacological (systemic and topical) and non pharmacological modalities for the alleviation of pain in people with DPN. We identified English language articles concerning studies with novel agents (animal or human) targeting symptomatic relief of painful diabetic neuropathy. Results: Though the pathophysiology of pain in DPN is complex, a better understanding of pain pathways (peripheral and central) have helped to identify potential targets for therapeutic success. Studies of pharmacological agents acting on various aspects of pain pathways including m-opioid receptor agonistnorepinephrine reuptake inhibitor (MONRI), cannabinoid receptor, dual serotonin-nor-adrenergic (SNRI)-and triple dopamine reuptake inhibitor (SNDRI), purinergic receptors and sodium channel v1.7 blockers have undergone trials in humans and shown to improve pain symptoms and quality of life in people with DPN. A few other investigational agents targeting acetylcholine receptor, vanilloid channel, chemokine signaling, micro-RNA or mesenchymal stem cell based therapies (animal studies) have demonstrated promise in alleviation of pain. Topical agents like high-dose lidocaine, capsaicin, clonidine, amitriptyline and ketamine may benefit refractory neuropathic pain. Conclusions: Novel MONRI, SNRI and cannabinoid receptor agonists have shown some promise for neuropathic pain relief in human trials, but await regulatory approvals. However, most of the novel pharmacological agents (systemic or topical) require appropriately powered placebo-controlled studies for clinical usage in painful diabetic neuropathy. (C) 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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