title: Gabapentin enhances the morphine anti-nociceptive effect in neuropathic pain via the interleukin-10-heme oxygenase-1 signalling pathway in rats.
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.
authors.affiliation: Pain Management Center, Shanghai Six People's Hospital, Shanghai Jiaotong University, No. 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Bao
authors.forename: Quan-Hong
authors.initials: QH
authors.lastname: Zhou
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Zeng
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Du
mesh_terms: D000588:Amines / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000077206:Gabapentin; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D053583:Interleukin-1beta; D015850:Interleukin-6; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C017803:zinc protoporphyrin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D051547:Heme Oxygenase-1