Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice

S. Lee; S. H. Jang; M. Suzuki-Narita; S. Gregoire; M. Millecamps; L. S. Stone

doi:10.1016/j.joca.2021.06.014

Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice

S. Lee, S. H. Jang, M. Suzuki-Narita, S. Gregoire, M. Millecamps, L. S. Stone

Anesthesiology

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Objective: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model. Methods: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1β, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1β, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR. Results: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1β, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males. Conclusions: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.

Original language	English (US)
Pages (from-to)	110-123
Number of pages	14
Journal	Osteoarthritis and Cartilage
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.joca.2021.06.014
State	Published - Jan 2022

Bibliographical note

Funding Information:
This work was supported by Canadian Institutes of Health Research grant MOP-142291 to LSS and MM. SL was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation . The authors thank the staff of the McGill University Comparative Medicine and Animal Resources Centre (CMARC), and Lina Naso, HyungMo Kang, Raquel Farias, Michael Ogundeji for their support.

Funding Information:
This work was supported by Canadian Institutes of Health Research grant MOP-142291 to LSS and MM. SL was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation. The authors thank the staff of the McGill University Comparative Medicine and Animal Resources Centre (CMARC), and Lina Naso, HyungMo Kang, Raquel Farias, Michael Ogundeji for their support.

Publisher Copyright:
© 2021 The Authors

Keywords

Cytokines
Inflammation
Macrophages
Running
SPARC-null

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't
Comparative Study

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10.1016/j.joca.2021.06.014

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title = "Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice",

abstract = "Objective: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model. Methods: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1β, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1β, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR. Results: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1β, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males. Conclusions: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.",

keywords = "Cytokines, Inflammation, Macrophages, Running, SPARC-null",

author = "S. Lee and Jang, {S. H.} and M. Suzuki-Narita and S. Gregoire and M. Millecamps and Stone, {L. S.}",

note = "Funding Information: This work was supported by Canadian Institutes of Health Research grant MOP-142291 to LSS and MM. SL was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation . The authors thank the staff of the McGill University Comparative Medicine and Animal Resources Centre (CMARC), and Lina Naso, HyungMo Kang, Raquel Farias, Michael Ogundeji for their support. Funding Information: This work was supported by Canadian Institutes of Health Research grant MOP-142291 to LSS and MM. SL was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation. The authors thank the staff of the McGill University Comparative Medicine and Animal Resources Centre (CMARC), and Lina Naso, HyungMo Kang, Raquel Farias, Michael Ogundeji for their support. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2022",

month = jan,

doi = "10.1016/j.joca.2021.06.014",

language = "English (US)",

volume = "30",

pages = "110--123",

journal = "Osteoarthritis and Cartilage",

issn = "1063-4584",

publisher = "W.B. Saunders Ltd",

number = "1",

}

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T1 - Voluntary running attenuates behavioural signs of low back pain

T2 - dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice

AU - Lee, S.

AU - Jang, S. H.

AU - Suzuki-Narita, M.

AU - Gregoire, S.

AU - Millecamps, M.

AU - Stone, L. S.

N1 - Funding Information: This work was supported by Canadian Institutes of Health Research grant MOP-142291 to LSS and MM. SL was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation . The authors thank the staff of the McGill University Comparative Medicine and Animal Resources Centre (CMARC), and Lina Naso, HyungMo Kang, Raquel Farias, Michael Ogundeji for their support. Funding Information: This work was supported by Canadian Institutes of Health Research grant MOP-142291 to LSS and MM. SL was supported by the Catherine Bushnell postdoctoral fellowship from the Louise and Alan Edwards Foundation. The authors thank the staff of the McGill University Comparative Medicine and Animal Resources Centre (CMARC), and Lina Naso, HyungMo Kang, Raquel Farias, Michael Ogundeji for their support. Publisher Copyright: © 2021 The Authors

PY - 2022/1

Y1 - 2022/1

N2 - Objective: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model. Methods: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1β, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1β, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR. Results: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1β, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males. Conclusions: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.

AB - Objective: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model. Methods: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1β, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1β, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR. Results: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1β, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males. Conclusions: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.

KW - Cytokines

KW - Inflammation

KW - Macrophages

KW - Running

KW - SPARC-null

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Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice

Abstract

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