The Precursor of Resolvin D Series and Aspirin-triggered Resolvin D1 Display Anti-hyperalgesic Properties in Adjuvant-induced Arthritis in Rats

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2011 Mar 23

PMID 21418187

Citations 97

Authors

J F Lima-Garcia

R C Dutra

Kabs da Silva

E M Motta

M M Campos

J B Calixto

Affiliations

Soon will be listed here.

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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References

Cortes-Burgos L, Zweifel B, Settle S, Pufahl R, Anderson G, Hardy M . CJ-13610, an orally active inhibitor of 5-lipoxygenase is efficacious in preclinical models of pain. Eur J Pharmacol. 2009; 617(1-3):59-67. DOI: 10.1016/j.ejphar.2009.06.058. View

Bannenberg G, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger K . Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol. 2005; 174(7):4345-55. DOI: 10.4049/jimmunol.174.7.4345. View

Xu Z, Zhang L, Liu T, Park J, Berta T, Yang R . Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat Med. 2010; 16(5):592-7, 1p following 597. PMC: 2866054. DOI: 10.1038/nm.2123. View

Hegen M, Keith Jr J, Collins M, Nickerson-Nutter C . Utility of animal models for identification of potential therapeutics for rheumatoid arthritis. Ann Rheum Dis. 2007; 67(11):1505-15. DOI: 10.1136/ard.2007.076430. View

Vitor C, Figueiredo C, Hara D, Bento A, Mazzuco T, Calixto J . Therapeutic action and underlying mechanisms of a combination of two pentacyclic triterpenes, alpha- and beta-amyrin, in a mouse model of colitis. Br J Pharmacol. 2009; 157(6):1034-44. PMC: 2737662. DOI: 10.1111/j.1476-5381.2009.00271.x. View

Schaible H, Richter F, Ebersberger A, Boettger M, Vanegas H, Natura G . Joint pain. Exp Brain Res. 2009; 196(1):153-62. DOI: 10.1007/s00221-009-1782-9. View

Gilroy D, Lawrence T, Perretti M, Rossi A . Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov. 2004; 3(5):401-16. DOI: 10.1038/nrd1383. View

Spite M, Summers L, Porter T, Srivastava S, Bhatnagar A, Serhan C . Resolvin D1 controls inflammation initiated by glutathione-lipid conjugates formed during oxidative stress. Br J Pharmacol. 2009; 158(4):1062-73. PMC: 2785528. DOI: 10.1111/j.1476-5381.2009.00234.x. View

Narita M, Shimamura M, Imai S, Kubota C, Yajima Y, Takagi T . Role of interleukin-1beta and tumor necrosis factor-alpha-dependent expression of cyclooxygenase-2 mRNA in thermal hyperalgesia induced by chronic inflammation in mice. Neuroscience. 2008; 152(2):477-86. DOI: 10.1016/j.neuroscience.2007.10.039. View

10.

Schaible H, Ebersberger A, Segond von Banchet G . Mechanisms of pain in arthritis. Ann N Y Acad Sci. 2002; 966:343-54. DOI: 10.1111/j.1749-6632.2002.tb04234.x. View

11.

Schaible H, Grubb B . Afferent and spinal mechanisms of joint pain. Pain. 1993; 55(1):5-54. DOI: 10.1016/0304-3959(93)90183-P. View

12.

Serhan C . Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol. 2006; 25:101-37. DOI: 10.1146/annurev.immunol.25.022106.141647. View

13.

van Vollenhoven R . Treatment of rheumatoid arthritis: state of the art 2009. Nat Rev Rheumatol. 2009; 5(10):531-41. DOI: 10.1038/nrrheum.2009.182. View

14.

Lee K, Kang B, Lee H, Son S, Hwang S, Kim D . Spinal NF-kB activation induces COX-2 upregulation and contributes to inflammatory pain hypersensitivity. Eur J Neurosci. 2004; 19(12):3375-81. DOI: 10.1111/j.0953-816X.2004.03441.x. View

15.

Xu X, Lundberg J, Hokfelt T, Wiesenfeld-Hallin Z, Szallasi A . Effects of the capsaicin analogue resiniferatoxin on spinal nociceptive mechanisms in the rat: behavioral, electrophysiological and in situ hybridization studies. Brain Res. 1997; 752(1-2):52-60. DOI: 10.1016/s0006-8993(96)01444-8. View

16.

Manjavachi M, Quintao N, Campos M, Deschamps I, Yunes R, Nunes R . The effects of the selective and non-peptide CXCR2 receptor antagonist SB225002 on acute and long-lasting models of nociception in mice. Eur J Pain. 2009; 14(1):23-31. DOI: 10.1016/j.ejpain.2009.01.007. View

17.

Lawrence T, Willoughby D, Gilroy D . Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol. 2002; 2(10):787-95. DOI: 10.1038/nri915. View

18.

Leem J, Hwang J, Hwang S, Park H, Kim M, Choi Y . The role of peripheral N-methyl-D-aspartate receptors in Freund's complete adjuvant induced mechanical hyperalgesia in rats. Neurosci Lett. 2001; 297(3):155-8. DOI: 10.1016/s0304-3940(00)01662-1. View

19.

Firestein G . Evolving concepts of rheumatoid arthritis. Nature. 2003; 423(6937):356-61. DOI: 10.1038/nature01661. View

20.

Hay C, Trevethick M, Wheeldon A, Bowers J, de Belleroche J . The potential role of spinal cord cyclooxygenase-2 in the development of Freund's complete adjuvant-induced changes in hyperalgesia and allodynia. Neuroscience. 1997; 78(3):843-50. DOI: 10.1016/s0306-4522(96)00598-2. View