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

Authors

  • JF Lima-Garcia,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
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  • RC Dutra,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
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  • KABS da Silva,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
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  • EM Motta,

    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
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  • MM Campos,

    1. Faculty of Dentistry and Institute of Toxicology, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
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  • JB Calixto

    Corresponding author
    1. Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
      João B Calixto, Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Bloco D-CCB – Cx. Postal: 476, Florianópolis, Santa Catarina, 88040-900, Brazil. E-mail: calixto@farmaco.ufsc.br; calixto3@terra.com.br
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João B Calixto, Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Bloco D-CCB – Cx. Postal: 476, Florianópolis, Santa Catarina, 88040-900, Brazil. E-mail: calixto@farmaco.ufsc.br; calixto3@terra.com.br

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

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