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. 2022 Sep;179(18):4500-4515.
doi: 10.1111/bph.15897. Epub 2022 Jul 7.

RvD1 disrupts nociceptor neuron and macrophage activation and neuroimmune communication, reducing pain and inflammation in gouty arthritis in mice

Tiago H Zaninelli  1 , Victor Fattori  1   2 , Telma Saraiva-Santos  1 , Stephanie Badaro-Garcia  1 , Larissa Staurengo-Ferrari  1 , Ketlem C Andrade  1 , Nayara A Artero  1 , Camila R Ferraz  1 , Mariana M Bertozzi  1 , Fernanda Rasquel-Oliveira  1 , Marilia F Manchope  1 , Flávio A Amaral  3 , Mauro M Teixeira  3 , Sergio M Borghi  1 , Michael S Rogers  2 , Rubia Casagrande  4 , Waldiceu A Verri Jr  1
Affiliations
Free article

RvD1 disrupts nociceptor neuron and macrophage activation and neuroimmune communication, reducing pain and inflammation in gouty arthritis in mice

Tiago H Zaninelli et al. Br J Pharmacol. 2022 Sep.
Free article

Abstract

Background and purpose: Gouty arthritis is characterized by an intense inflammatory response to monosodium urate crystals (MSU), which induces severe pain. Current therapies are often ineffective in reducing gout-related pain. Resolvin D1 (RvD1) is a specialized pro-resolving lipid mediator with anti-inflammatory and analgesic proprieties. In this study, we evaluated the effects and mechanisms of action of RvD1 in an experimental mouse model of gouty arthritis, an aim that was not pursued previously in the literature.

Experimental approach: Male mice were treated with RvD1 (intrathecally or intraperitoneally) before or after intraarticular stimulation with MSU. Mechanical hyperalgesia was assessed using an electronic von Frey aesthesiometer. Leukocyte recruitment was determined by knee joint wash cell counting and immunofluorescence. IL-1β production was measured by ELISA. Phosphorylated NF-kB and apoptosis-associated speck-like protein containing CARD (ASC) were detected by immunofluorescence, and mRNA expression was determined by RT-qPCR. CGRP release was determined by EIA and immunofluorescence. MSU crystal phagocytosis was evaluated by confocal microscopy.

Key results: RvD1 inhibited MSU-induced mechanical hyperalgesia in a dose- and time-dependent manner by reducing leukocyte recruitment and IL-1β production in the knee joint. Intrathecal RvD1 reduced the activation of peptidergic neurons and macrophages as well as silenced nociceptor to macrophage communication and macrophage function. CGRP stimulated MSU phagocytosis and IL-1β production by macrophages. RvD1 downmodulated this phenomenon directly by acting on macrophages, and indirectly by inhibiting CGRP release and CGRP-dependent activation of macrophages.

Conclusions and implications: This study reveals a hitherto unknown neuro-immune axis in gouty arthritis that is targeted by RvD1.

Keywords: CGRP; MSU; gout; neuroimmune; phagocytosis; rheumatic diseases; specialized pro-resolving mediator.

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References

REFERENCES

    1. Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Beuve, A., Brouckaert, P., Bryant, C., Burnett, J. C., Farndale, R. W., Friebe, A., Garthwaite, J., … Waldman, S. A. (2021a). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Catalytic receptors. British Journal of Pharmacology, 178(S1), S264-S312. https://doi.org/10.1111/bph.15541
    1. Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Boison, D., Burns, K. E., Dessauer, C., Gertsch, J., Helsby, N. A., Izzo, A. A., Koesling, D., … Wong, S. S. (2021b). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes. British Journal of Pharmacology, 178(S1), S313-S411. https://doi.org/10.1111/bph.15542
    1. Alexander, S. P., Mathie, A., Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Aldrich, R. W., Attali, B., Baggetta, A. M., Becirovic, E., Biel, M., Bill, R. M., Catterall, W. A., … Zhu, M. (2021). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Ion channels. British Journal of Pharmacology, 178(S1), S157-S245. https://doi.org/10.1111/bph.15539
    1. Alexander, S. P. H., Roberts, R. E., Broughton, B. R. S., Sobey, C. G., George, C. H., Stanford, S. C., Cirino, G., Docherty, J. R., Giembycz, M. A., Hoyer, D., Insel, P. A., Izzo, A. A., Ji, Y., MacEwan, D. J., Mangum, J., & Wonnacott, S. (2018). Goals and practicalities of immunoblotting and immunohistochemistry: A guide for submission to the British Journal of Pharmacology. British Journal of Pharmacology, 175, 407-411. https://doi.org/10.1111/bph.14112
    1. Allen, B. L., Montague-Cardoso, K., Simeoli, R., Colas, R. A., Oggero, S., Vilar, B., McNaughton, P. A., Dalli, J., Perretti, M., Sher, E., & Malcangio, M. (2020). Imbalance of proresolving lipid mediators in persistent allodynia dissociated from signs of clinical arthritis. Pain, 161, 2155-2166. https://doi.org/10.1097/j.pain.0000000000001908

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