Implications and mechanism of action of gabapentin in neuropathic pain

Abstract

Gabapentin is an anti-epileptic agent but now it is also recommended as first line agent in neuropathic pain, particularly in diabetic neuropathy and post herpetic neuralgia. α2δ-1, an auxillary subunit of voltage gated calcium channels, has been documented as its main target and its specific binding to this subunit is described to produce different actions responsible for pain attenuation. The binding to α2δ-1 subunits inhibits nerve injury-induced trafficking of α1 pore forming units of calcium channels (particularly N-type) from cytoplasm to plasma membrane (membrane trafficking) of pre-synaptic terminals of dorsal root ganglion (DRG) neurons and dorsal horn neurons. Furthermore, the axoplasmic transport of α2δ-1 subunits from DRG to dorsal horns neurons in the form of anterograde trafficking is also inhibited in response to gabapentin administration. Gabapentin has also been shown to induce modulate other targets including transient receptor potential channels, NMDA receptors, protein kinase C and inflammatory cytokines. It may also act on supra-spinal region to stimulate noradrenaline mediated descending inhibition, which contributes to its anti-hypersensitivity action in neuropathic pain.

The distinctive significance of analgesic drugs and olfactory stimulants on learned pain in mice

“…It acts on the presynaptic GABAergic terminals in the locus coeruleus and presynaptically reduces GABAergic synaptic transmission. Consequently, in neuropathic pain states, the inhibitory influence on neurons in the locus coeruleus is removed, leading to activation of the descending noradrenergic system (Kukkar et al, 2013;Snedecor et al, 2013). Our finding that the CR was resistant to gabapentin may explain the limitations of this drug in the treatment of chronic pain syndromes that include a CR.…”

Anticonvulsant and antinociceptive activity of new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in mice

“…A particularly important issue is the treatment of neuropathic pain. This type of pain is caused by a disease or injury of the nervous system and is characterized by distinctive symptoms, such as spontaneous nociceptor activity, decreased nociceptive threshold (allodynia), and increased response to supra-threshold stimuli (hyperalgesia) (Kukkar et al, 2013). There are various conditions associated with neuropathic pain, like diabetic neuropathy, post-herpetic neuralgia, trigeminal neuralgia, and cancer.…”

“…In particular, recent studies have documented beneficial effects of anticonvulsant drugs in ameliorating different types of neuropathic pain. Gabapentin and pregabalin have proven to be potent antiallodynic drugs in the treatment of diabetic neuropathic pain and post-herpetic neuralgia, whereas carbamazepine and oxcarbazepine are efficacious agents for the treatment of trigeminal neuralgia (Kukkar et al, 2013;Mendlik and Uritsky, 2015). However, evidence suggests that neuropathic pain is variable in its severity, as well as in response to cure.…”

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What Has Been Investigated, and What Is in the Pipeline?

“…Low dose topiramate has also been used in the treatment of alcohol dependence [181]. Three other drugs which may also offer some utility for smoking cessation include zonisamide which is in the same class of medications (marketed as Topamax) [182]; gabapentin, an antiepileptic drug that acts on voltage gated calcium channels (particularly N and Ltypes) and binds to GABA-B receptors to inhibit their function [183,184]; and tiagabine, a blocker of GABA reuptake (marketed under Gabitril) [185,186].…”