Alleviation of pain in painful diabetic neuropathy

ABSTRACT

Introduction: Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain management treatment is currently available.

Areas covered: The origin of PDN is enigmatic, and the evidence-based therapeutic guidelines therefore consist only of antidepressants and antiepileptics as first-line recommended drugs. This article relates to a MEDLINE/PubMed systematic search (2005-2015).

Expert opinion: The results of the meta-analysis from the aspect of the efficacy of amitriptyline, duloxetine, venlafaxine, gabapentin and pregabalin are favorable, but the placebo response rate is relatively high in patients with neuropathic pain. For personalization of the medication of PDN patients, the optimum dosing, the genotyping of the metabolizing enzymes and optimum biomarkers are needed. As concerns the future perspectives, specific sodium channel subtype inhibitors acting on peripheral nociceptive neurons or modified T-type voltage-gated calcium channel blockers may be promising targets for pharmaceutical innovations. Another attractive strategy for the treatment is based on the effects of monoclonal antibodies against nerve growth factor, sodium channels, specific receptor and cytokines. Botulinum toxin A, capsaicin patch and spinal cord stimulation therapies are the nearest future therapeutic options for the treatment of PDN patients.

KEYWORDS:

• Antidepressants
• antiepileptics
• diabetes
• metabolism
• painful neuropathy
• pharmacodynamics
• pharmacokinetics
• treatment

Article highlights

• The pathomechanism of painful diabetic neuropathy is unknown, and therefore only symptomatic non-specific treatment is available.

• As a tricyclic antidepressant, amitriptyline has multimodal action, and is effective with a favorable number needed to treat, but it exerts many unfavorable adverse eventAEs related to its pharmacological profile.

• The selective serotonin-norepinephrine reuptake inhibitor duloxetine has been subjected to pharmacogenomic studies.

• Venlafaxine has a strong dose-dependent effect and due to its extended release formulation, the treatment-related adverse events are low.

• Gabapentin as an antiepileptic has no metabolism and no drug–drug interactions with a high adherence level.

• Pregabalin as a gabapentinoid with linear kinetics, has been strongly recommended for the treatment of painful diabetic neuropathy.

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Declaration of interests

This work was supported by the project TÁMOP-4.2.2.A-11/1/KONV-2012-0052, by the Hungarian Brain Research Programme (NAP, Grant No. KTIA_13_NAP-A-III/9. and by the MTA-SZTE Neuroscience Research Group of the Hungarian Academy of Sciences and the University of Szeged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.