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-alleviation 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)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(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 Ttype 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 channel, 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.

Therapeutic Approaches for Peripheral and Central Neuropathic Pain

“…Due to its high frequency, PDP was the prototype disorder for the development of anti-NP therapeutic strategies. The first-line drugs in PDP as recommended by different international therapeutic guidelines are the following: duloxetine, gabapentin, pregabalin, TCAs (amitriptyline), and venlafaxine ER (extended release) [12, 39, 40]. Cochrane meta-analyses concluded that gabapentin, pregabalin, and duloxetine are effective for pain relief in PDP [31, 41, 42].…”

Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

“…The development of DNP is dependent on two critical pathogenic factors: the metabolic factor and the vascular factor. The primary metabolic mechanisms include hyperglycemia-activated polyhydric alcohol pathway, accumulation of sorbitol and fructose, inositol reduction, non-enzymatic protein glycosylation, and oxidative stress 3 , 4 . The vascular mechanism is the consequence of diabetes-induced systemic microvascular damage; it leads to energy and nutrient deficiency, inducing a hypoxic and ischemic injury of neural cells.…”

Reproducibility of a battery of human evoked pain models to detect pharmacological effects of analgesic drugs

“…Pregabalin is a structural analogue of the inhibitory neurotransmitter gamma‐aminobutyric acid (GABA) and binds to the α 2 δ auxiliary subunit of voltage‐gated calcium channels in the central nervous system. In clinical trials, pregabalin has been shown to have analgesic effects in diabetic neuropathy, post‐herpetic neuralgia and spinal cord injury (Offord & Isom, ; Patel & Dickenson, ; Tatji et al, ). In controlled clinical trials involving peripheral neuropathic pain, 35% of pregabalin‐treated patients had an improvement in their pain scores (Satoh et al, ).…”