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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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Il-10 anti-body abolished the effect of gabapentin on morphine in SNL exposed rats. a IL-10 protein levels were measured in the experimental group. Co-administration of gabapentin (25 μg) with morphine (30 μg) for 7 days twice daily significantly increased IL-10 expression in rats; anti-IL-10 antibody (10 μg) neutralised IL-10 expression induced by this co-administration; gabapentin delayed morphine tolerance development in SNL-exposed rats, as measured using the tail–flick (b) and Von Frey (c) tests. The maximum anti-nociceptive effect of morphine occurred on days 1–3. From days 4 to 7, there was no difference between the morphine and saline groups. When gabapentin was co-administered with morphine and prevented morphine tolerance. The anti-IL-10 antibody partially reversed the potentiating effect of gabapentin on morphine in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group; $p < 0.05, $$p < 0.01, $$$p < 0.001 compared with the gabapentin/morphine group
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Fig2: Il-10 anti-body abolished the effect of gabapentin on morphine in SNL exposed rats. a IL-10 protein levels were measured in the experimental group. Co-administration of gabapentin (25 μg) with morphine (30 μg) for 7 days twice daily significantly increased IL-10 expression in rats; anti-IL-10 antibody (10 μg) neutralised IL-10 expression induced by this co-administration; gabapentin delayed morphine tolerance development in SNL-exposed rats, as measured using the tail–flick (b) and Von Frey (c) tests. The maximum anti-nociceptive effect of morphine occurred on days 1–3. From days 4 to 7, there was no difference between the morphine and saline groups. When gabapentin was co-administered with morphine and prevented morphine tolerance. The anti-IL-10 antibody partially reversed the potentiating effect of gabapentin on morphine in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group; $p < 0.05, $$p < 0.01, $$$p < 0.001 compared with the gabapentin/morphine group

Mentions: In SNL rats, chronic morphine tolerance was attenuated by co-administration of gabapentin with morphine twice a day for 7 days in the behavioural tests (Fig. 2b, c). The efficacy of morphine was diminished after 4 days of injection, but the efficacy was maintained on day 7 when morphine was co-administered with gabapentin. The anti-IL-10 antibody abolished the effect of gabapentin on morphine. Moreover, there was no difference in anti-nociception effect in the saline group or the gabapentin and anti-IL-10 antibody-treated animals.Fig. 2


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)

Il-10 anti-body abolished the effect of gabapentin on morphine in SNL exposed rats. a IL-10 protein levels were measured in the experimental group. Co-administration of gabapentin (25 μg) with morphine (30 μg) for 7 days twice daily significantly increased IL-10 expression in rats; anti-IL-10 antibody (10 μg) neutralised IL-10 expression induced by this co-administration; gabapentin delayed morphine tolerance development in SNL-exposed rats, as measured using the tail–flick (b) and Von Frey (c) tests. The maximum anti-nociceptive effect of morphine occurred on days 1–3. From days 4 to 7, there was no difference between the morphine and saline groups. When gabapentin was co-administered with morphine and prevented morphine tolerance. The anti-IL-10 antibody partially reversed the potentiating effect of gabapentin on morphine in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group; $p < 0.05, $$p < 0.01, $$$p < 0.001 compared with the gabapentin/morphine group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Il-10 anti-body abolished the effect of gabapentin on morphine in SNL exposed rats. a IL-10 protein levels were measured in the experimental group. Co-administration of gabapentin (25 μg) with morphine (30 μg) for 7 days twice daily significantly increased IL-10 expression in rats; anti-IL-10 antibody (10 μg) neutralised IL-10 expression induced by this co-administration; gabapentin delayed morphine tolerance development in SNL-exposed rats, as measured using the tail–flick (b) and Von Frey (c) tests. The maximum anti-nociceptive effect of morphine occurred on days 1–3. From days 4 to 7, there was no difference between the morphine and saline groups. When gabapentin was co-administered with morphine and prevented morphine tolerance. The anti-IL-10 antibody partially reversed the potentiating effect of gabapentin on morphine in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group; $p < 0.05, $$p < 0.01, $$$p < 0.001 compared with the gabapentin/morphine group
Mentions: In SNL rats, chronic morphine tolerance was attenuated by co-administration of gabapentin with morphine twice a day for 7 days in the behavioural tests (Fig. 2b, c). The efficacy of morphine was diminished after 4 days of injection, but the efficacy was maintained on day 7 when morphine was co-administered with gabapentin. The anti-IL-10 antibody abolished the effect of gabapentin on morphine. Moreover, there was no difference in anti-nociception effect in the saline group or the gabapentin and anti-IL-10 antibody-treated animals.Fig. 2

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