Pregabalin in neuropathic pain: evidences and possible mechanisms

Abstract

Pregabalin is an antagonist of voltage gated Ca2+ channels and specifically binds to alpha-2-delta subunit to produce antiepileptic and analgesic actions. It successfully alleviates the symptoms of various types of neuropathic pain and presents itself as a first line therapeutic agent with remarkable safety and efficacy. Preclinical studies in various animal models of neuropathic pain have shown its effectiveness in treating the symptoms like allodynia and hyperalgesia. Clinical studies in different age groups and in different types of neuropathic pain (peripheral diabetic neuropathy, fibromyalgia, post-herpetic neuralgia, cancer chemotherapy-induced neuropathic pain) have projected it as the most effective agent either as monotherapy or in combined regimens in terms of cost effectiveness, tolerability and overall improvement in neuropathic pain states. Preclinical studies employing pregabalin in different neuropathic pain models have explored various molecular targets and the signaling systems including Ca2+ channel-mediated neurotransmitter release, activation of excitatory amino acid transporters (EAATs), potassium channels and inhibition of pathways involving inflammatory mediators. The present review summarizes the important aspects of pregabalin as analgesic in preclinical and clinical studies as well as focuses on the possible mechanisms.

Keywords: Pregabalin; diabetic neuropathy; neuropathic pain; post-herpetic neuralgia..

Fig. (1)

The mechanism of action for pain alleviation by pregabalin: Pregabalin blocks the VGCC and hence decrease glutamate and sensory neuropeptides (substance P and CGRP) release at synapse by decreasing Ca2+ influx. EAATs (excitatory amino acid transporters) activity is increased by pregabalin which caused more decrease in synaptic availability of glutamate. Decreased glutamate levels further inhibited the activation of NMDA and decreased the neuronal firing. Additionally pregabalin also activates the KATP channels, which also contributes to inhibition of neuronal excitation. Pregabalin through all these pathways ultimately provides significant pain relief in various neuropathic pain states.