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

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Ahlström , F H G , Mätlik , K , Viisanen , H , Blomqvist , K J , Liu , X , Lilius , T O , Sidorova , Y , Kalso , E A & Rauhala , P V 2021 , ' Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats ' , Molecular Neurobiology , vol. 58 , no. 10 , pp. 5396-5419 . https://doi.org/10.1007/s12035-021-02447-1

Title: Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats
Author: Ahlström, F. H. G.; Mätlik, K.; Viisanen, H.; Blomqvist, K. J.; Liu, X.; Lilius, T. O.; Sidorova, Y.; Kalso, E. A.; Rauhala, P. V.
Contributor organization: Department of Pharmacology
Faculty of Medicine
University of Helsinki
INDIVIDRUG - Individualized Drug Therapy
Research Programs Unit
Medicum
Institute of Biotechnology
Molecular Systems Biology
Helsinki Institute of Life Science HiLIFE
HUSLAB
Department of Clinical Pharmacology
HUS Emergency Medicine and Services
Helsinki University Hospital Area
Divisions of Faculty of Pharmacy
HUS Perioperative, Intensive Care and Pain Medicine
Eija Kalso / Principal Investigator
Department of Diagnostics and Therapeutics
Clinicum
Anestesiologian yksikkö
Pekka Rauhala / Principal Investigator
Date: 2021-10
Language: eng
Number of pages: 24
Belongs to series: Molecular Neurobiology
ISSN: 0893-7648
DOI: https://doi.org/10.1007/s12035-021-02447-1
URI: http://hdl.handle.net/10138/340509
Abstract: 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.
Subject: Neuropathic pain
Rat
Sex-differences
Behaviour
Transcriptomics
Proteomics
DIPEPTIDYL PEPTIDASE-IV
NEUROPATHIC PAIN
FEMALE RATS
MAP KINASE
ACTIVATION
CONTRIBUTES
LOCALIZATION
RECEPTORS
MICROGLIA
CANCER
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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