Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats.

Autor: Ahlström FHG; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland. fredrik.ahlstrom@helsinki.fi.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland. fredrik.ahlstrom@helsinki.fi., Mätlik K; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland., Viisanen H; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland., Blomqvist KJ; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland., Liu X; Systems Biology/Pathology Research Group and Proteomics Unit, Institute of Biotechnology, HiLIFE, University of Helsinki, 00014, Helsinki, Finland., Lilius TO; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Norre Allé 14, DK-2200, Copenhagen, Denmark.; Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Tukholmankatu 8 C, 00014, Helsinki, Finland.; Emergency Medicine, University of Helsinki and Department of Emergency Medicine and Services, Helsinki University Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland., Sidorova Y; Laboratory of Molecular Neuroscience, Institute of Biotechnology, HiLIFE, University of Helsinki, Viikinkaari 5D, 00014, Helsinki, Finland., Kalso EA; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.; Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, Helsinki University Hospital and University of Helsinki, Stenbäckinkatu 9, P.O. Box 440, 00029, Helsinki, Finland.; SleepWell Research Programme, Faculty of Medicine, University of Helsinki, Haartmaninkatu 3, 00014, Helsinki, Finland., Rauhala PV; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8 (Biomedicum 1), 00014, Helsinki, Finland.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2021 Oct; Vol. 58 (10), pp. 5396-5419. Date of Electronic Publication: 2021 Jul 30.
DOI: 10.1007/s12035-021-02447-1
Abstrakt: Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.
(© 2021. The Author(s).)
Databáze: MEDLINE
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