Intrathecal Gabapentin Increases Interleukin-10 Expression and Inhibits Pro-Inflammatory Cytokine in a Rat Model of Neuropathic Pain

Abstract

We examined the possible anti-inflammatory mechanisms of gabapentin in the attenuation of neuropathic pain and the interaction between the anti-allodynic effects of gabapentin and interleukin-10 (IL-10) expression in a rat model of neuropathic pain. The anti-allodynic effect of intrathecal gabapentin was examined over a 7-day period. The anti-allodynic effects of IL-10 was measured, and the effects of anti-IL-10 antibody on the gabapentin were assessed. On day 7, the concentrations of pro-inflammatory cytokines and IL-10 were measured. Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-α, 316.0 ± 69.7 pg/mL vs 88.8 ± 24.4 pg/mL; IL-1β, 1,212.9 ± 104.5 vs 577.4 ± 97.1 pg/mL; IL-6, 254.0 ± 64.8 pg/mL vs 125.5 ± 44.1 pg/mL; IL-10, 532.1 ± 78.7 pg/mL vs 918.9 ± 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody. Expression of pro-inflammatory cytokines was significantly attenuated by daily injections of IL-10. The anti-allodynic effects of gabapentin may be caused by upregulation of IL-10 expression in the spinal cord, which leads to inhibition of the expression of pro-inflammatory cytokines in the spinal cords.

Correlation Dependencies between Nociceptive Sensitivity and Cytokine Level in Biological Fluids of Rats after Administration of Lipopolysaccharide

“…Importantly, the concentration of an anti-infl ammatory cytokine IL-10 in peripheral blood serum of rats correlates negatively with the emotional and perceptual components of nociception. Our results provide indirect support for published data that IL-10 has an antinociceptive effect on mammals, which is probably associated with its ability to inhibit the synthesis of pro-infl ammatory cytokines [9]. Negative correlations were found between the contents of antiinfl ammatory cytokines IL-4 and IL-10 in peripheral blood serum of rats after intraperitoneal injection of LPS and baseline parameters for the emotional and perceptual components of nociception.…”

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

“…Gabapentin (Gb) also enhances the antinociceptive effect of Mo and attenuates Mo tolerance probably through upregulation of the anti-inflammatory cytokine IL-10 and inhibition of proinflammatory cytokines in the rat spinal cord (Lee et al, 2013;Bao et al, 2014); effects that may explain the decreased TNF-α levels in the Gb-treated rats from our investigation. Rossi and colleagues (2013) demonstrated that Gb also reduced reactive gliosis and dendritic loss caused by glutamate excitotoxicity after pilocarpine-induced status epilecticus.…”

Does preemptive gabapentin modulate cytokine response in total knee arthroplasty? A placebo controlled study

“…22 Apart from that, in a rat model of neuropathic pain, antinociception was observed as a result of inhibited expression of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 by gabapentin. 23 Unfortunately, we could not find many studies showing a one-to-one correspondence with our study to compare our results. Some other analgesic agents have been tried in this aspect in a few other studies.…”