Analgesic Effect of Intrathecal Gabapentin in a Rat Model of Persistent Muscle Pain

Abstract

ObjectiveTo evaluate the analgesic effect of intrathecal gabapentin therapy on secondary hyperalgesia in a rat model of persistent muscle pain.MethodsIntrathecal catheters were implanted into rats. Mechanical secondary hyperalgesia was induced by repeated intramuscular injections of acidic solution into the gastrocnemius muscle. Gabapentin was administrated intrathecally. Rats were allocated to control and experimental (gabapentin 30, 100, 300, and 1,000 µg) group. After gabapentin administration, mechanical withdrawal threshold was measured every 15 minutes and the motor function was measured 30 minutes later.ResultsMechanical hyperalgesia was evoked after the second acidic buffer injection. There was a significant improvement on the mechanical threshold after administration of 100, 300, and 1,000 µg gabapentin compared to pre-injection and the control group. The analgesic effect continued for 105, 135, and 210 minutes, respectively. To discern side effects, motor function was measured. Motor function was preserved in both groups after gabapentin administration, except for rats who received 1,000 µg gabapentin.ConclusionIntrathecal gabapentin administration produces dose-dependent improvements in mechanical hyperalgesia in a persistent muscle pain rat model. This implicates the central nervous system as having a strong influence on the development of persistent mechanical hyperalgesia. These results are helpful in understanding the pathophysiology of secondary hyperalgesia and in the treatment of patients with chronic muscle pain.

Gabapentin Effects on PKC-ERK1/2 Signaling in the Spinal Cord of Rats with Formalin-Induced Visceral Inflammatory Pain

“…Through Western blot analysis, our data show that gabapentin significantly diminishes the membrane translocation of PKC and the phosphorylation levels of ERK1/2, suggesting that the analgesic effect of gabapentin is mediated through the suppression of PKC and ERK1/2 signaling pathways. In addition, numerous studies have identified gabapentin as a NMDA receptor blocker and a voltage-gated calcium channel blocker [ 6 – 8 ]. NMDA and calcium receptor activation in the peripheral and central nervous systems have been shown to be involved in the development and maintenance of various pain states, including neuropathic pain and visceral pain [ 14 , 15 , 39 ].…”

“…In 2002, the USA Food and Drug Administration approved gabapentin, a γ-aminobutyric acid derivative, for clinical use in the treatment of neuropathic pain. Since then, gabapentin has been extensively applied in the field of analgesia [ 6 – 9 ]. Preliminary data from animal experiments have confirmed the analgesic effects of gabapentin on visceral pain, but the mechanism of this effects remains unknown [ 10 , 11 ].…”

“…In a variety of pain models, including visceral pain, the persistence of chronic pain is known to occur through constitutive activation of N-methyl-D-aspartate (NMDA) receptors and calcium channels [ 14 – 16 ], which in turn, causes increased activation of PKC and ERK1/2 signaling, resulting in the chronic hyper-excitability of neurons involved in pain transmission [ 17 ]. In addition, the mechanism of gabapentin-mediated analgesia in treating pain has been shown to occur through the inhibition of NMDA receptors and calcium channels in the central nervous system [ 6 – 8 , 18 ]. Therefore, we hypothesized that the gabapentin-induced analgesia in visceral inflammatory pain is mediated through an inhibitory effect on the PKC-ERK1/2 signaling.…”

Avaliação do efeito da gabapentina em modelo de dor muscular crônica em ratos.

“…Desta forma, o efeito antinociceptivo da gabapentina em modelo de dor muscular crônica induzida por CFA foi constatado. Estes resultados corroboram com um único estudo prévio de dor musculoesquelética tratada com gabapentina que demonstrou seu efeito analgésico em ratos com hiperalgesia mecânica após injeção de salina ácida no músculo gastrocnêmio (Kang et al, 2014).…”

“…Estudos têm demonstrado que a gabapentina pode inibir respostas dolorosas por meio de sua ligação à subunidade α2/δ-1 de canais de cálcio dependentes de voltagem presente em neurônios e redução de substâncias como glutamato, substância P, NF-kB e CGRP (Fink et al, 2000;Kukkar et al, 2013;Park et al, 2008;Quintero et al, 2011;Yaksh, 2006). Além disso, sabe-se que a gabapentina apenas prejudica funções motoras em doses elevadas (Kang et al, 2014).…”