Mechanisms of the Antinociceptive Action of Gabapentin

Abstract

Abstract. Gabapentin, a γ-aminobutyric acid (GABA) analogue anticonvulsant, is also an effective analgesic agent in neuropathic and inflammatory, but not acute, pain systemically and intrathecally. Other clinical indications such as anxiety, bipolar disorder, and hot flashes have also been proposed. Since gabapentin was developed, several hypotheses had been proposed for its action mechanisms. They include selectively activating the heterodimeric GABA B receptors consisting of GABA B1a and GABA B2 subunits, selectively enhancing the NMDA current at GABAergic interneurons, or blocking AMPA-receptor-mediated transmission in the spinal cord, binding to the L-α-amino acid transporter, activating ATP-sensitive K + channels, activating hyperpolarization-activated cation channels, and modulating Ca 2+ current by selectively binding to the specific binding site of [3 H]gabapentin, the α 2 δ subunit of voltage-dependent Ca 2+ channels. Different mechanisms might be involved in different therapeutic actions of gabapentin. In this review, we summarized the recent progress in the findings proposed for the antinociceptive action mechanisms of gabapentin and suggest that the α 2 δ subunit of spinal N-type Ca 2+ channels is very likely the analgesic action target of gabapentin.

Preventive Analgesia and Novel Strategies for the Prevention of Chronic Post-Surgical Pain

“…The lack of standardized gabapentin doses between studies may have contributed to inconsistencies in the drug's efficacy at reducing the incidence and severity of CPSP. It has been well documented that the absorption profile of gabapentin in humans is inconsistent due to the active and saturable aamino acid transport system [29]. Thus, the bioavailability of any given dose varies from 35-90 % [29].…”

“…It has been well documented that the absorption profile of gabapentin in humans is inconsistent due to the active and saturable aamino acid transport system [29]. Thus, the bioavailability of any given dose varies from 35-90 % [29]. Without plasma samples, one cannot confirm therapeutic drug concentrations of gabapentin, as such it is possible that the higher doses of gabapentin may enable therapeutic plasma levels needed to demonstrate preventive effects with respect to the reduction of CPSP.…”

Gabapentin Attenuates the Activation of Transient Receptor Potential A1 by Cinnamaldehyde

“…(Garry et al, 2005;Cheng and Chiou, 2006;Arnold et al, 2007;Dworkin et al, 2007;Gilron et al, 2007;Nishiyori et al, 2008). The mechanism of the analgesic action of gabapentin is still not clear but the recent reports proposed that gabapentin might act on several receptors and ion channels expressed in the dorsal root ganglia (DRG) or in the spinal cord dorsal horn neurons (Luo et al, 2001).…”

Impact of oral meloxicam administered alone or in combination with gabapentin on experimentally induced lameness in beef calves1

“…Gabapentin is a γ-aminobutyric acid analogue originally developed for the treatment of spastic disorders and epilepsy in humans (Cheng and Chiou, 2006). Studies have established that GABA is also effective for the management of chronic pain of inflammatory or neuropathic origin (Hurley et al, 2002).…”

“…Inflammatory pain responds modestly to treatment with nonsteroidal anti-inflammatory drugs (NSAID; Whay et al, 2005;Flower et al, 2008) but neuropathic pain is considered refractory to the effects of NSAID (Woolf and Mannion, 1999). Gabapentin (GABA) is a γ-aminobutyric acid analogue used extensively for the management of chronic pain in humans (Hurley et al, 2002;Cheng and Chiou, 2006). Meloxicam (MEL) is a NSAID that is approved outside the United States as an adjunctive therapy of acute respiratory disease, diarrhea, and acute mastitis.…”