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IL-1 receptor antagonist improves morphine and buprenorphine efficacy in a rat neuropathic pain model.

Abstract
An interesting research and therapeutic problem is the reduced beneficial efficacy of opioids in the treatment of neuropathic pain. The present study sought to investigate the potential role of IL-1 family members in this phenomenon. We studied the time course of changes in IL-1alpha, IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist mRNA and protein levels experienced by rats after chronic constriction injury (CCI) of the sciatic nerve using qRT-PCR and Western blot analysis. In CCI-exposed rats, spinal levels of IL-1alpha mRNA were slightly downregulated on the 7th day, and protein levels were not changed on the 7th and 14th days. Levels of IL-1 receptor antagonist and IL-1 receptor type I were slightly upregulated in the ipsilateral part of the spinal cord on the 7th and 14th days; however, protein levels were not changed at those time points. Interestingly, we observed that IL-1beta mRNA and protein levels were strongly elevated in the ipsilateral part of the dorsal spinal cord on the 7th and 14th days following CCI. Moreover, in rats exposed to a single intrathecal administration of an IL-1 receptor antagonist (100 ng i.t.) on the 7th and 14th day following CCI, symptoms of neuropathic pain were attenuated, and the analgesic effects of morphine (2.5 µg i.t.) and buprenorphine (2.5 µg i.t.) were enhanced. In summary, restoration of the analgesic activity of morphine and buprenorphine by blockade of IL-1 signaling suggests that increased IL-1beta responses may account for the decreased analgesic efficacy of opioids observed in the treatment of neuropathy.
AuthorsDominika Pilat, Ewelina Rojewska, Agnieszka M Jurga, Anna Piotrowska, Wioletta Makuch, Barbara Przewlocka, Joanna Mika
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 764 Pg. 240-248 (Oct 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
PMID26043968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • Analgesics, Opioid
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1alpha
  • Interleukin-1beta
  • RNA, Messenger
  • Buprenorphine
  • Morphine
Topics
  • Analgesics, Opioid (pharmacology, therapeutic use)
  • Animals
  • Buprenorphine (pharmacology, therapeutic use)
  • Hyperalgesia (drug therapy, metabolism)
  • Interleukin 1 Receptor Antagonist Protein (genetics, metabolism)
  • Interleukin-1alpha (genetics, metabolism)
  • Interleukin-1beta (genetics, metabolism)
  • Male
  • Morphine (pharmacology, therapeutic use)
  • Neuralgia (drug therapy, metabolism)
  • RNA, Messenger (metabolism)
  • Rats, Wistar
  • Sciatic Nerve (injuries)
  • Spinal Cord (drug effects, metabolism)
  • Treatment Outcome

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