The role of neutrophils in pain: systematic review and meta-analysis of animal studies.

Autor:	Huerta MÁ; Department of Pharmacology, Faculty of Medicine, University of Granada, Granada, Spain.; Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.; Biosanitary Research Institute ibs.GRANADA, Granada, Spain., Molina-Álvarez M; Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Rey Juan Carlos University, Asociated Unit I+D+i Instituto de Química Médica (IQM) CSIC-URJC, Alcorcón, Spain.; High Performance Experimental Pharmacology Research Group, Rey Juan Carlos University (PHARMAKOM), Alcorcón, Spain., García MM; Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Rey Juan Carlos University, Asociated Unit I+D+i Instituto de Química Médica (IQM) CSIC-URJC, Alcorcón, Spain.; High Performance Experimental Pharmacology Research Group, Rey Juan Carlos University (PHARMAKOM), Alcorcón, Spain., Tejada MA; Department of Pharmacology, Faculty of Medicine, University of Granada, Granada, Spain.; Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.; Biosanitary Research Institute ibs.GRANADA, Granada, Spain., Goicoechea C; Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Rey Juan Carlos University, Asociated Unit I+D+i Instituto de Química Médica (IQM) CSIC-URJC, Alcorcón, Spain.; High Performance Experimental Pharmacology Research Group, Rey Juan Carlos University (PHARMAKOM), Alcorcón, Spain., Ghasemlou N; Pain Chronobiology & Neuroimmunology Laboratory, Departments of Anesthesiology and Biomedical & Molecular Sciences, Queen's University, Kingston, ON, Canada., Ruiz-Cantero MC; Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain., Cobos EJ; Department of Pharmacology, Faculty of Medicine, University of Granada, Granada, Spain.; Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.; Biosanitary Research Institute ibs.GRANADA, Granada, Spain.; Teófilo Hernando Institute for Drug Discovery, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1097/j.pain.0000000000003450
Abstrakt:	Abstract: The peripheral inflammatory response is an attractive therapeutic target for pain treatment. Neutrophils are the first circulating inflammatory cells recruited to sites of injury, but their contribution to pain outcomes is unclear. We performed a systematic review and meta-analysis of original preclinical studies, which evaluated the effect of preemptive neutrophil depletion on pain outcomes (PROSPERO registration number: CRD42022364004). Literature search (PubMed, January 19, 2023) identified 49 articles, which were meta-analyzed using a random-effects model. The risk of bias was evaluated using SYRCLE's tool. The pooled effect considering all studies showed that neutrophil depletion induced a consistent pain reduction. Inflammatory, joint, neuropathic, and visceral pain showed significant pain alleviation by neutrophil depletion with medium-large effect sizes. However, muscle and postoperative pain were not significantly alleviated by neutrophil depletion. Further analysis showed a differential contribution of neutrophils to pain outcomes. Neutrophils had a higher impact on mechanical hyperalgesia, followed by nociceptive behaviors and mechanical allodynia, with a smaller contribution to thermal hyperalgesia. Interspecies (mice or rats) differences were not appreciated. Analyses regarding intervention unveiled a lower pain reduction for some commonly used methods for neutrophil depletion, such as injection of antineutrophil serum or an anti-Gr-1 antibody, than for other agents such as administration of an anti-Ly6G antibody, fucoidan, vinblastine, CXCR1/2 inhibitors, and etanercept. In conclusion, the contribution of neutrophils to pain depends on pain etiology (experimental model), pain outcome, and the neutrophil depletion strategy. Further research is needed to improve our understanding on the mechanisms of these differences. (Copyright © 2024 International Association for the Study of Pain.)
Databáze:	MEDLINE
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