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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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Effects of IL-10 on the anti-nociceptive effects of morphine in SNL rats. Time-course of the tail–flick (a) and Von Frey filament (b) tests after 7 days of daily injection of various doses (1, 2 or 5 μg) of recombinant rat IL-10 (rrIL-10) combined with continuous i.t. morphine injection. A large dose injection of rrIL-10 (5 μg) with morphine for 7 days produced a significantly anti-nociceptive effect, whilst rrIL-10 (5 μg) administered alone did not produce an anti-nociceptive effect in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group
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Fig3: Effects of IL-10 on the anti-nociceptive effects of morphine in SNL rats. Time-course of the tail–flick (a) and Von Frey filament (b) tests after 7 days of daily injection of various doses (1, 2 or 5 μg) of recombinant rat IL-10 (rrIL-10) combined with continuous i.t. morphine injection. A large dose injection of rrIL-10 (5 μg) with morphine for 7 days produced a significantly anti-nociceptive effect, whilst rrIL-10 (5 μg) administered alone did not produce an anti-nociceptive effect in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group

Mentions: Recombinant rat IL-10 (rrIL-10) was used to investigate the effect of IL-10 in the attenuation of the development of morphine tolerance. Daily intrathecally injections of rrIL-10 (5 μg) alone did not produce any anti-nociceptive effect via the 7-day treatment compared with the saline group (Fig. 3a, b). The anti-nociceptive effect of continuous morphine injection was partially maintained via a daily intrathecal rrIL-10 (5 μg) injection during tolerance induction but not by an injection of lower doses of rrIL-10 (1 or 2 μg) compared with the morphine group. These data demonstrated that IL-10 attenuated morphine tolerance in neuropathic pain rats.Fig. 3


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)

Effects of IL-10 on the anti-nociceptive effects of morphine in SNL rats. Time-course of the tail–flick (a) and Von Frey filament (b) tests after 7 days of daily injection of various doses (1, 2 or 5 μg) of recombinant rat IL-10 (rrIL-10) combined with continuous i.t. morphine injection. A large dose injection of rrIL-10 (5 μg) with morphine for 7 days produced a significantly anti-nociceptive effect, whilst rrIL-10 (5 μg) administered alone did not produce an anti-nociceptive effect in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Effects of IL-10 on the anti-nociceptive effects of morphine in SNL rats. Time-course of the tail–flick (a) and Von Frey filament (b) tests after 7 days of daily injection of various doses (1, 2 or 5 μg) of recombinant rat IL-10 (rrIL-10) combined with continuous i.t. morphine injection. A large dose injection of rrIL-10 (5 μg) with morphine for 7 days produced a significantly anti-nociceptive effect, whilst rrIL-10 (5 μg) administered alone did not produce an anti-nociceptive effect in SNL rats (n = 6, each). ***p < 0.001 compared with the saline group; ###p < 0.001 compared with the morphine group
Mentions: Recombinant rat IL-10 (rrIL-10) was used to investigate the effect of IL-10 in the attenuation of the development of morphine tolerance. Daily intrathecally injections of rrIL-10 (5 μg) alone did not produce any anti-nociceptive effect via the 7-day treatment compared with the saline group (Fig. 3a, b). The anti-nociceptive effect of continuous morphine injection was partially maintained via a daily intrathecal rrIL-10 (5 μg) injection during tolerance induction but not by an injection of lower doses of rrIL-10 (1 or 2 μg) compared with the morphine group. These data demonstrated that IL-10 attenuated morphine tolerance in neuropathic pain rats.Fig. 3

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