title: Norisoboldine attenuates inflammatory pain via the adenosine A1 receptor.
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.
  
  
  CONCLUSIONS
  Our data demonstrate that NOR produces the analgesic effect in inflammatory pain by a mechanism related to the adenosine system.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China; Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, USA.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: Q
authors.initials: Q
authors.lastname: Lu
authors.forename: G
authors.initials: G
authors.lastname: Chou
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Pan
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D043682:Receptor, Adenosine A1; C464745:norisoboldine