The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats
Article first published online: 22 AUG 2011
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
British Journal of Pharmacology
Volume 164, Issue 2, pages 278–293, September 2011
How to Cite
Lima-Garcia, J., Dutra, R., da Silva, K., Motta, E., Campos, M. and Calixto, J. (2011), The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats. British Journal of Pharmacology, 164: 278–293. doi: 10.1111/j.1476-5381.2011.01345.x
- Issue published online: 22 AUG 2011
- Article first published online: 22 AUG 2011
- Accepted manuscript online: 21 MAR 2011 01:27PM EST
- Received; 13 September 2010; Revised; 4 February 2011; Accepted; 7 February 2011
- RvD series precursor;
- inflammatory pain;
BACKGROUND AND PURPOSE 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).
EXPERIMENTAL APPROACH 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.
KEY 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 AND IMPLICATIONS 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