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Ultra-low dose naloxone restores the antinocicepitve effect of morphine in PTX-treated rats: association of IL-10 upregulation in the spinal cord.

Authors: Lin, YS  Tsai, RY  Shen, CH  Chien, CC  Tsai, WY  Guo, SL  Wong, CS 
Citation: Lin YS, etal., Life Sci. 2012 Sep 4;91(5-6):213-20. doi: 10.1016/j.lfs.2012.07.005. Epub 2012 Jul 20.
Pubmed: (View Article at PubMed) PMID:22820166
DOI: Full-text: DOI:10.1016/j.lfs.2012.07.005

AIMS: Ultra-low dose naloxone has been shown to restore the antinociceptive effect of morphine in pertussis toxin (PTX)-treated rats by suppressing spinal microglia activation and inhibiting inflammatory cytokine expression. This study was further investigated the mechanism by which ultra-low dose naloxone promotes analgesia in pertussis toxin-treated rats. MAIN METHODS: Male Wistar rats were implanted with an intrathecal (i.t.) catheter and injected either saline or PTX (1 mug). Four days later, rats randomly received either saline, or ultra-low dose naloxone, or recombinant rat interleukin-10 (rrIL-10) (1 mug) injection followed by saline or morphine (10 mug) 30 min later. In some experiments, mouse anti-rat IL-10 antibody (10 mug) was injected intrathecally into PTX injected rats daily on days 4, 5, 6, and 7. On day 7, ultra-low dose naloxone was given 1h after antibody injection with or without subsequent morphine injection. KEY FINDINGS: PTX injection induced notable thermal hyperalgesia and mechanical allodynia. Injection of ultra-low dose naloxone preserved the antinociceptive effect of morphine in PTX-treated rats and associated an increasing of IL-10 protein expression. Intrathecal injection rrIL-10 alone or in combination with morphine, not only reversed mechanical allodynia but also partially restored the antinociceptive effect of morphine; injection of anti-rat IL-10 antibody attenuated the effect of morphine plus ultra-low dose naloxone on mechanical allodynia and completely inhibited the antinociceptive effect of morphine. SIGNIFICANCE: These results indicate that intrathecal ultra-low dose naloxone induces IL-10 expression in spinal neuron and microglia, which suppresses PTX-induced neuroinflammation and restores the antinociceptive effect of morphine.

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RGD ID: 7364827
Created: 2013-10-01
Species: All species
Last Modified: 2013-10-01
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.