Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine

Molecular and Cellular Neurosciences
Dominika PilatJoanna Mika

Abstract

Currently, the low efficacy of antinociceptive drugs for the treatment of neuropathic pain is a major therapeutic problem. Here, we show the potential role of interleukin (IL)-18 signaling in this phenomenon. IL-18 is an important molecule that performs various crucial functions, including the alteration of nociceptive transmission in response to neuropathic pain. We have studied the changes in the mRNA and protein levels (qRT-PCR and Western blot analysis, respectively) of IL-18, IL-18-binding protein (IL-18BP) and the IL-18 receptor (IL-18R) over time in rats following chronic constriction injury (CCI) of the sciatic nerve. Our study demonstrated that the spinal levels of IL-18BP were slightly downregulated at days 7 and 14 in the rats subjected to CCI. In contrast, the IL-18 and IL-18R mRNA expression and protein levels were elevated in the ipsilateral spinal cord on days 2, 7 and 14. Moreover, in rats exposed to a single intrathecal administration of IL-18BP (50 and 100 ng) 7 or 14 days following CCI, symptoms of neuropathic pain were attenuated, and the analgesia pursuant to morphine and buprenorphine (0.5 and 2.5 μg) was enhanced. In summary, the restoration of the analgesic activity of morphine and buprenorphine via the ...Continue Reading

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Citations

Mar 20, 2018·Current Opinion in Supportive and Palliative Care·Alexandra M DurrantNicholas Beazley-Long
Aug 21, 2018·Pharmacological Reports : PR·Klaudia Kwiatkowski, Joanna Mika
Mar 25, 2017·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Klaudia KwiatkowskiJoanna Mika
May 23, 2020·Brain, Behavior, and Immunity·Katrien PletinckxTorsten R Dunkern
Mar 4, 2021·The Journal of Experimental Medicine·Hana StarobovaIrina Vetter
May 26, 2020·Pharmacology & Therapeutics·Bao-Chun JiangYong-Jing Gao
Oct 17, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Cosmin I Ciotu, Michael J M Fischer

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