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Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain
H E L E N E L A N G E V I N , M D
O S H E R C E N T E R F O R I N T E G R A T I V E M E D I C I N E H A R V A R D M E D I C A L S C H O O L
B R I G H A M A N D W O M E N ’ S H O S P I T A L
Musculoskeletal system Immune system
Can body movements influence immune processes
such as inflammation?
Fear
Normal wound healing vs. persistent inflammation and fibrosis
resolution failed resolution
chronic
inflammation
fibrosis
acute inflammation
Fear
Normal wound healing vs. persistent inflammation and fibrosis
resolution failed resolution
chronic
inflammation
fibrosis
acute inflammation
Subcutaneous
carrageenan
injection model
Fear
Normal wound healing vs. persistent inflammation and fibrosis
resolution failed resolution
chronic
inflammation
fibrosis
acute inflammation
stretch
sham
Subcutaneous
carrageenan
injection model
Daily stretching for 10 minutes reduces chronic inflammation of connective tissue
stretch
sham
Corey et al. PLoS One 2012
* p<0.05
** p<0.01
N=24 rats
2 weeks after carrageenan injection
n
Dietary Ω-3 fatty acids EPA, DHA
Resolution Neutrophils
Pro-resolving mediators
Injury
Inflammation and resolution pathways
n
Dietary Ω-3 fatty acids EPA, DHA
Failed resolution
Chronic inflammation
Fibrosis
Neutrophils
Pro-resolving mediators
Pro-inflammatory mediators
Injury
Persistent inflammation and failed resolution
Effect of stretching on acute inflammation 48 hours after carrageenan injection
* p<0.05
** p<0.01
*** p<0.001
Berrueta et al. J Cell Physiol 2016
Effect of stretching on pro-resolving and pro-inflammatory mediators within the inflammatory lesion
* p<0.05
** p<0.01
Berrueta et al. J Cell Physiol 2016
Effect of stretching on neutrophil migration and resolvin production ex vivo
** p<0.01
Berrueta et al. J Cell Physiol 2016
Biomechanical consequences of connective tissue injury
Decreased mobility of fascia layers (adhesions)
Post-injury
Normal
Ultrasound evaluation of thoracolumbar fascia in chronic low back pain
•107 human subjects
•60 chronic LBP
•47 No-LBP
•LBP >12 mo
•Matched for age, sex, BMI
BMC Musculoskel Dis 2009
**P<0.001 *P<0.01
Ultrasound evaluation of thoracolumbar fascia in chronic low back pain
N=107 subjects
BMC Musculoskel Dis 2009
Shear plane motion of connective tissue layers within thoracolumbar fascia
Head Feet
No Low Back Pain Low Back Pain
Thoracolumbar fascia shear strain in subjects with and without low back pain
N=116
p<.001
BMC Musculoskel Dis 2011
Effect of stretching on connective tissue thickness in scleroderma GVHD model
*
No stretch Stretch
*p<.001
#p<.01
Xiong Frontiers Immunol 2017
*
Effect of stretching on connective tissue mobility in scleroderma GvDH model
*
Segment A
Segment B
No stretch Stretch
#p<.01 #
Xiong Frontiers Immunol 2017
Experimental design 20 pigs randomized for 8
weeks to:
• Control
• Connective tissue injury
• Movement restriction
• Injury plus movement
restriction
20 pigs randomized for 8 weeks to:
• Control
• Connective tissue injury
• Movement restriction
• Injury plus movement restriction
Fear
Model linking connective tissue, inflammation, fibrosis and musculoskeletal pain
resolution failed resolution
reduced tissue
mobility
chronic
inflammation
fibrosis
acute inflammation
PAIN
Fear of
movement
Fear
How would stretching impact this model?
inflammation resolution
improved tissue mobility
acute inflammation
PAIN
decreased
fear of
movement
Effect of stretching on thoracolumbar fascia mobility in pigs 4 weeks after removing hobbles
ANOVA p<.05
Acknowledgements
Sarah Corey
Nicole Bouffard
Jim Fox
Cathryn Koptiuch
Sharon Henry
Funding from:
Osher Foundation
NCCIH RO1 AT003479, RO1 AT004400, RO1 AT009267 and F31 AT005559
University of Vermont
Lisbeth Berrueta
Sara Olenich
Igla Muskaj
Charles Serhan
Antonios Aliprantis
Katia Urso
Taylor Butler
Osher Center Connective Tissue Lab Harvard Medical School Brigham and Women’s Hospital