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Gabapentin enhances the morphine anti-nociceptive effect in neuropathic pain via the interleukin-10-heme oxygenase-1 signalling pathway in rats.

Bao YH, Zhou QH, Chen R, Xu H, Zeng LL, Zhang X, Jiang W, Du DP - J. Mol. Neurosci. (2014)

Bottom Line: Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were measured.Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression.Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Pain Management Center, Shanghai Six People's Hospital, Shanghai Jiaotong University, No. 600 Yishan Road, Shanghai, 200233, People's Republic of China.

ABSTRACT
In the present study, we investigated the anti-inflammatory mechanisms by which gabapentin enhances morphine anti-nociceptive effect in neuropathic pain in rats and the interaction between the anti-nociceptive effects of gabapentin on morphine and the interleukin (IL)-10-heme-oxygenase (HO)-1 signal pathway in a rat model of neuropathic pain. The neuropathic pain model was induced via a left L5/6 spinal nerve ligation (SNL) in rats. The anti-nociceptive effect of gabapentin and IL-10 on morphine was examined over a 7-day period, and the effects of the anti-IL-10 and HO-1 inhibitor zinc protoporphyrin (ZnPP) on gabapentin/morphine co-injection were assessed. Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were measured. Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression. The effect of gabapentin on morphine was partially blocked using the anti-IL-10 antibody or the HO-1 inhibitor zinc protoporphyrin. Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.

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Anti-IL-10 antibody dose-dependently reversed gabapentin-induced heme oxygenase-1 (HO-1) expression in gabapentin/morphine co-injected SNL rats. Western blotting analyses of HO-1 in the spinal cord dorsal horn of the various treatment groups; β-actin was used as the internal control. Importantly, the upregulated HO-1 protein observed in animals co-administered with gabapentin and morphine was suppressed by different concentrations of anti-IL-10 antibody (n = 6, each). **p < 0.01, ***p < 0.001 compared with the saline group; ##p < 0.01, ###p < 0.001 compared with the morphine group; $$p < 0.01 compared with the gabapentin/morphine group
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Fig4: Anti-IL-10 antibody dose-dependently reversed gabapentin-induced heme oxygenase-1 (HO-1) expression in gabapentin/morphine co-injected SNL rats. Western blotting analyses of HO-1 in the spinal cord dorsal horn of the various treatment groups; β-actin was used as the internal control. Importantly, the upregulated HO-1 protein observed in animals co-administered with gabapentin and morphine was suppressed by different concentrations of anti-IL-10 antibody (n = 6, each). **p < 0.01, ***p < 0.001 compared with the saline group; ##p < 0.01, ###p < 0.001 compared with the morphine group; $$p < 0.01 compared with the gabapentin/morphine group

Mentions: Co-injection of gabapentin and morphine for 7 days significantly increased HO-1 expression compared with the morphine-treated animal group (Fig. 4). In addition, daily i.t. injection of different doses of anti-IL-10 antibody for 7 days dose-dependently reversed the gabapentin-induced upregulation of HO-1 expression. These results suggested that IL-10 is involved in the increase in HO-1 expression in gabapentin/morphine–injected neuropathic pain rats.Fig. 4


Gabapentin enhances the morphine anti-nociceptive effect in neuropathic pain via the interleukin-10-heme oxygenase-1 signalling pathway in rats.

Bao YH, Zhou QH, Chen R, Xu H, Zeng LL, Zhang X, Jiang W, Du DP - J. Mol. Neurosci. (2014)

Anti-IL-10 antibody dose-dependently reversed gabapentin-induced heme oxygenase-1 (HO-1) expression in gabapentin/morphine co-injected SNL rats. Western blotting analyses of HO-1 in the spinal cord dorsal horn of the various treatment groups; β-actin was used as the internal control. Importantly, the upregulated HO-1 protein observed in animals co-administered with gabapentin and morphine was suppressed by different concentrations of anti-IL-10 antibody (n = 6, each). **p < 0.01, ***p < 0.001 compared with the saline group; ##p < 0.01, ###p < 0.001 compared with the morphine group; $$p < 0.01 compared with the gabapentin/morphine group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4125805&req=5

Fig4: Anti-IL-10 antibody dose-dependently reversed gabapentin-induced heme oxygenase-1 (HO-1) expression in gabapentin/morphine co-injected SNL rats. Western blotting analyses of HO-1 in the spinal cord dorsal horn of the various treatment groups; β-actin was used as the internal control. Importantly, the upregulated HO-1 protein observed in animals co-administered with gabapentin and morphine was suppressed by different concentrations of anti-IL-10 antibody (n = 6, each). **p < 0.01, ***p < 0.001 compared with the saline group; ##p < 0.01, ###p < 0.001 compared with the morphine group; $$p < 0.01 compared with the gabapentin/morphine group
Mentions: Co-injection of gabapentin and morphine for 7 days significantly increased HO-1 expression compared with the morphine-treated animal group (Fig. 4). In addition, daily i.t. injection of different doses of anti-IL-10 antibody for 7 days dose-dependently reversed the gabapentin-induced upregulation of HO-1 expression. These results suggested that IL-10 is involved in the increase in HO-1 expression in gabapentin/morphine–injected neuropathic pain rats.Fig. 4

Bottom Line: Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were measured.Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression.Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Pain Management Center, Shanghai Six People's Hospital, Shanghai Jiaotong University, No. 600 Yishan Road, Shanghai, 200233, People's Republic of China.

ABSTRACT
In the present study, we investigated the anti-inflammatory mechanisms by which gabapentin enhances morphine anti-nociceptive effect in neuropathic pain in rats and the interaction between the anti-nociceptive effects of gabapentin on morphine and the interleukin (IL)-10-heme-oxygenase (HO)-1 signal pathway in a rat model of neuropathic pain. The neuropathic pain model was induced via a left L5/6 spinal nerve ligation (SNL) in rats. The anti-nociceptive effect of gabapentin and IL-10 on morphine was examined over a 7-day period, and the effects of the anti-IL-10 and HO-1 inhibitor zinc protoporphyrin (ZnPP) on gabapentin/morphine co-injection were assessed. Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were measured. Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression. The effect of gabapentin on morphine was partially blocked using the anti-IL-10 antibody or the HO-1 inhibitor zinc protoporphyrin. Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.

Show MeSH
Related in: MedlinePlus