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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Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats. / Ahlstrom, F. H. G.; Matlik, K.; Viisanen, H.; Blomqvist, K. J.; Liu, X.; Lilius, T. O.; Sidorova, Y.; Kalso, E. A.; Rauhala, P. V.

In: Molecular Neurobiology, Vol. 58, 2021, p. 5396–5419.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ahlstrom, FHG, Matlik, K, Viisanen, H, Blomqvist, KJ, Liu, X, Lilius, TO, Sidorova, Y, Kalso, EA & Rauhala, PV 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, pp. 5396–5419. https://doi.org/10.1007/s12035-021-02447-1

APA

Ahlstrom, F. H. G., Matlik, 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, 58, 5396–5419. https://doi.org/10.1007/s12035-021-02447-1

Vancouver

Ahlstrom FHG, Matlik K, Viisanen H, Blomqvist KJ, Liu X, Lilius TO et al. Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats. Molecular Neurobiology. 2021;58:5396–5419. https://doi.org/10.1007/s12035-021-02447-1

Author

Ahlstrom, F. H. G. ; Matlik, K. ; Viisanen, H. ; Blomqvist, K. J. ; Liu, X. ; Lilius, T. O. ; Sidorova, Y. ; Kalso, E. A. ; Rauhala, P. V. / Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats. In: Molecular Neurobiology. 2021 ; Vol. 58. pp. 5396–5419.

Bibtex

@article{fed94ca8ce734c46a589044fa4aa063f,
title = "Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats",
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.",
keywords = "Neuropathic pain, Rat, Sex-differences, Behaviour, Transcriptomics, Proteomics, DIPEPTIDYL PEPTIDASE-IV, NEUROPATHIC PAIN, FEMALE RATS, MAP KINASE, ACTIVATION, CONTRIBUTES, LOCALIZATION, RECEPTORS, MICROGLIA, CANCER",
author = "Ahlstrom, {F. H. G.} and K. Matlik and H. Viisanen and Blomqvist, {K. J.} and X. Liu and Lilius, {T. O.} and Y. Sidorova and Kalso, {E. A.} and Rauhala, {P. V.}",
year = "2021",
doi = "10.1007/s12035-021-02447-1",
language = "English",
volume = "58",
pages = "5396–5419",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats

AU - Ahlstrom, F. H. G.

AU - Matlik, K.

AU - Viisanen, H.

AU - Blomqvist, K. J.

AU - Liu, X.

AU - Lilius, T. O.

AU - Sidorova, Y.

AU - Kalso, E. A.

AU - Rauhala, P. V.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Neuropathic pain

KW - Rat

KW - Sex-differences

KW - Behaviour

KW - Transcriptomics

KW - Proteomics

KW - DIPEPTIDYL PEPTIDASE-IV

KW - NEUROPATHIC PAIN

KW - FEMALE RATS

KW - MAP KINASE

KW - ACTIVATION

KW - CONTRIBUTES

KW - LOCALIZATION

KW - RECEPTORS

KW - MICROGLIA

KW - CANCER

U2 - 10.1007/s12035-021-02447-1

DO - 10.1007/s12035-021-02447-1

M3 - Journal article

C2 - 34331199

VL - 58

SP - 5396

EP - 5419

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

ER -

ID: 275817266