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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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Time course of paw withdrawal threshold after spinal nerve ligation (SNL) and sham surgery over a 7-day period. All data points are expressed as the mean ± SEM (n = 6, each). *p < 0.05, ***p < 0.001 compared with sham group
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Fig1: Time course of paw withdrawal threshold after spinal nerve ligation (SNL) and sham surgery over a 7-day period. All data points are expressed as the mean ± SEM (n = 6, each). *p < 0.05, ***p < 0.001 compared with sham group

Mentions: As shown in Fig. 1, 1 week after SNL, the mechanical withdrawal threshold of the hind paw ipsilateral to the nerve injury was significantly decreased in SNL rats (p < 0.001) compared to the sham-operated animals. In addition, no difference in the withdrawal threshold was observed in the contralateral hind paw. These results suggested that the neuropathic pain model with monolateral mechanical allodynia has been successfully established and was consistent with previous reports.Fig. 1


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)

Time course of paw withdrawal threshold after spinal nerve ligation (SNL) and sham surgery over a 7-day period. All data points are expressed as the mean ± SEM (n = 6, each). *p < 0.05, ***p < 0.001 compared with sham group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Time course of paw withdrawal threshold after spinal nerve ligation (SNL) and sham surgery over a 7-day period. All data points are expressed as the mean ± SEM (n = 6, each). *p < 0.05, ***p < 0.001 compared with sham group
Mentions: As shown in Fig. 1, 1 week after SNL, the mechanical withdrawal threshold of the hind paw ipsilateral to the nerve injury was significantly decreased in SNL rats (p < 0.001) compared to the sham-operated animals. In addition, no difference in the withdrawal threshold was observed in the contralateral hind paw. These results suggested that the neuropathic pain model with monolateral mechanical allodynia has been successfully established and was consistent with previous reports.Fig. 1

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