Willemen, Hanneke L. D. M. and Eijkelkamp, Niels and Carbajal, Anibal Garza and Wang, Huijing and Mack, Matthias and Zijlstra, Jitske and Heijnen, Cobi J. and Kavelaars, Annemieke (2014) Monocytes/Macrophages Control Resolution of Transient Inflammatory Pain. JOURNAL OF PAIN, 15 (5). pp. 496-506. ISSN 1526-5900,
Full text not available from this repository. (Request a copy)Abstract
Insights into mechanisms governing resolution of inflammatory pain are of great importance for many chronic pain-associated diseases. Here we investigate the role of macrophages/monocytes and the anti-inflammatory cytokine interleukin-10 (IL-10) in the resolution of transient inflammatory pain. Depletion of mice from peripheral monocytes/macrophages delayed resolution of intraplantar IL-1 beta- and carrageenan-induced inflammatory hyperalgesia from 1 to 3 days to >1 week. Intrathecal administration of a neutralizing IL-10 antibody also markedly delayed resolution of IL-1 beta- and carrageenan-induced inflammatory hyperalgesia. Recently, we showed that IL-1 beta- and carrageenan-induced hyperalgesia is significantly prolonged in LysM-GRK2(+/-) mice, which have reduced levels of G-protein-coupled receptor kinase 2 (GRK2) in LysM(+) myeloid cells. Here we show that adoptive transfer of wild-type, but not of GRK2(+/-), bone marrow-derived monocytes normalizes the resolution of IL-1 beta-induced hyperalgesia in LysM-GRK2(+/-) mice. Adoptive transfer of IL-10(-/-) bone marrow-derived monocytes failed to normalize the duration of IL-1 beta-induced hyperalgesia in LysM-GRK2(+/-) mice. Mechanistically, we show that GRK2(+/-) macrophages produce less IL-10 in vitro. In addition, intrathecal IL-10 administration attenuated IL-1 beta-induced hyperalgesia in LysM-GRK2(+/-) mice, whereas it had no effect in wild-type mice. Our data uncover a key role for monocytes/macrophages in promoting resolution of inflammatory hyperalgesia via a mechanism dependent on IL-10 signaling in dorsal root ganglia. Perspective: We show that IL-10-producing monocytes/macrophages promote resolution of transient inflammatory hyperalgesia. Additionally, we show that reduced monocyte/macrophage GRK2 impairs resolution of hyperalgesia and reduces IL-10 production. We propose that low GRK2 expression and/or impaired IL-10 production by monocytes/macrophages represent peripheral biomarkers for the risk of developing chronic pain after inflammation. Published by Elsevier Inc. on behalf of the American Pain Society
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCED MECHANICAL ALLODYNIA; DORSAL-ROOT GANGLIA; NEUROPATHIC PAIN; SPINAL-CORD; NERVE INJURY; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; PATHOLOGICAL PAIN; PERIPHERAL-NERVE; TNF-ALPHA; Monocytes/macrophages; G-protein-coupled receptor kinase 2; interleukin-10; inflammatory pain |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Nov 2019 09:42 |
| Last Modified: | 13 Nov 2019 09:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10246 |
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