title: The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats.
abstract: OBJECTIVE
  Resolution of inflammation is mediated by endogenous molecules with anti-inflammatory and pro-resolving activities and they have generated new possibilities for the treatment of inflammatory diseases. Here, we have investigated the possible anti-hyperalgesic effects of two lipids, aspirin-triggered resolvin D1 (AT-RvD1) and its precursor, 17(R)-hydroxy-4Z,7Z,10Z,13Z,15E,17R,19Z-docosahexaenoic acid (17(R)HDoHE).
  
  
  METHODS
  The anti-hyperalgesic effects of both lipid mediators were evaluated, using mechanical and thermal stimuli, at different time-points in adjuvant-induced arthritis in rats. Cytokine levels were measured, and immunohistochemistry and real-time PCR for pro-inflammatory mediators were also performed.
  
  
  RESULTS
  The precursor of resolvin D series, 17(R)HDoHE, given systemically, inhibited the development and the maintenance of mechanical hyperalgesia in acute inflammation. Such effects were likely to be associated with modulation of both NF-κB and COX-2 in dorsal root ganglia and spinal cord. 17(R)HDoHE was also effective against sub-chronic pain. Unexpectedly, repeated treatment with 17(R)HDoHE did not modify paw and joint oedema in the sub-chronic model, while joint stiffness was prevented. Notably, AT-RvD1 exhibited marked anti-hyperalgesic effects in acute inflammation when given systemically. The efficacy of long-term treatment with either 17(R)HDoHE or AT-RvD1 was partly related to decreased production of TNF-α and IL-1β in rat hind paw.
  
  
  CONCLUSIONS
  Our findings provide fresh evidence for the anti-hyperalgesic properties of 17(R)HDoHE and its pro-resolution metabolite AT-RvD1. Such lipid mediators might be useful for treating pain associated with acute or chronic inflammation. LINKED ARTICLE This article is commented on by Xu and Ji, pp. 274-277 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01348.x.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: J F
authors.initials: JF
authors.lastname: Lima-Garcia
authors.forename: R C
authors.initials: RC
authors.lastname: Dutra
authors.forename: Kabs
authors.initials: K
authors.lastname: da Silva
authors.forename: E M
authors.initials: EM
authors.lastname: Motta
authors.forename: M M
authors.initials: MM
authors.lastname: Campos
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000150:complications; D002908:Chronic Disease; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant / Q000633:toxicity; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats
chemical_list: C518399:resolvin D1; D004281:Docosahexaenoic Acids; D005620:Freund's Adjuvant; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid