The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats.

Abstract

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.

• Authors: J F Lima-Garcia, R C Dutra, Kabs da Silva, E M Motta, M M Campos, J B Calixto
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 164 Issue 2 Pg. 278-93 (Sep 2011) ISSN: 1476-5381 [Electronic] England
• PMID: 21418187 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• resolvin D1
• Docosahexaenoic Acids
• Freund's Adjuvant
• 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid

Topics

• Animals
• Arthritis (chemically induced, complications)
• Chronic Disease
• Docosahexaenoic Acids (chemistry, therapeutic use)
• Dose-Response Relationship, Drug
• Freund's Adjuvant (toxicity)
• Hot Temperature
• Inflammation (chemically induced, complications)
• Male
• Pain (drug therapy, etiology)
• Rats