Norisoboldine attenuates inflammatory pain via the adenosine A1 receptor

X. Gao, Q. Lu, G. Chou, Z. Wang, R. Pan, Y. Xia, Huijuan Hu, Yue Dai

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background Norisoboldine (NOR) is a benzylisoquinoline alkaloid isolated from Radix Linderae, a traditional Chinese medicine. Our previous studies have demonstrated that it produces anti-inflammatory and anti-rheumatoid arthritis effects. Methods The present study was undertaken to explore the analgesic effects of NOR and its potential mechanism in the formalin test and the acetic acid writhing test. Results Oral administration of NOR dose dependently attenuated the formalin-induced pain responses in the second phase, and reduced formalin-induced paw oedema. It also diminished acetic acid-induced writhing responses but had no effect on acute thermal pain in the hotplate test. The mechanistic studies suggested that the adenosine system, but not the opioid receptor system, is involved in NOR-induced antinociception. Naloxone, a non-selective opioid receptor antagonist, had no effect on NOR-induced analgesic action. However, caffeine (a non-selective adenosine receptor antagonist) completely reversed the analgesic effect of NOR in formalin-induced nociceptive responses in the second phase, and 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, a selective adenosine A1 receptor antagonist) completely inhibited NOR-induced analgesia in both formalin-induced nociceptive responses and acetic acid-induced writhing responses. In addition, NOR reduced formalin-induced activation of extracellular signal-regulated kinase and calcium/calmodulin-dependent protein kinase II in the spinal cord, which is also blocked by DPCPX. Furthermore, NOR decreased forskolin-evoked cyclic adenosine monophosphate levels in mouse spinal cord neuronal cultures through the adenosine A1 receptor. Conclusion Our data demonstrate that NOR produces the analgesic effect in inflammatory pain by a mechanism related to the adenosine system.

Original languageEnglish (US)
Pages (from-to)939-948
Number of pages10
JournalEuropean Journal of Pain (United Kingdom)
Volume18
Issue number7
DOIs
StatePublished - Aug 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

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