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Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain HELENE LANGEVIN, MD OSHER CENTER FOR INTEGRATIVE MEDICINE HARVARD MEDICAL SCHOOL BRIGHAM AND WOMEN’S HOSPITAL
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Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Aug 18, 2019

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Page 1: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 2: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

2 Immune

system

Disconnected physiological systems

Page 3: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

3 Immune

system

Cross system integration

Page 4: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

4 Immune

system

Cross system integration

Page 5: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Musculoskeletal system Immune system

Page 6: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Musculoskeletal system

Page 7: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Immune system

Page 8: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Musculoskeletal system Immune system

Can body movements influence immune processes

such as inflammation?

Page 9: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Fear

Normal wound healing vs. persistent inflammation and fibrosis

resolution failed resolution

chronic

inflammation

fibrosis

acute inflammation

Page 10: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Fear

Normal wound healing vs. persistent inflammation and fibrosis

resolution failed resolution

chronic

inflammation

fibrosis

acute inflammation

Subcutaneous

carrageenan

injection model

Page 11: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Fear

Normal wound healing vs. persistent inflammation and fibrosis

resolution failed resolution

chronic

inflammation

fibrosis

acute inflammation

stretch

sham

Subcutaneous

carrageenan

injection model

Page 12: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 13: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Effect of active and passive stretching 2 weeks after carrageenan injection

* p<0.05

** p<0.01

Page 14: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

n

Dietary Ω-3 fatty acids EPA, DHA

Resolution Neutrophils

Pro-resolving mediators

Injury

Inflammation and resolution pathways

Page 15: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 16: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 17: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 18: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Effect of stretching on neutrophil migration and resolvin production ex vivo

** p<0.01

Berrueta et al. J Cell Physiol 2016

Page 19: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Biomechanical consequences of connective tissue injury

Decreased mobility of fascia layers (adhesions)

Post-injury

Normal

Page 20: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 21: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

**P<0.001 *P<0.01

Ultrasound evaluation of thoracolumbar fascia in chronic low back pain

N=107 subjects

BMC Musculoskel Dis 2009

Page 22: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Connective tissue layers within thoracolumbar fascia

Page 23: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Shear plane motion of connective tissue layers within thoracolumbar fascia

Head Feet

No Low Back Pain Low Back Pain

Page 24: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Thoracolumbar fascia shear strain in subjects with and without low back pain

N=116

p<.001

BMC Musculoskel Dis 2011

Page 25: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Effect of stretching on connective tissue thickness in scleroderma GVHD model

*

No stretch Stretch

*p<.001

#p<.01

Xiong Frontiers Immunol 2017

Page 26: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

*

Effect of stretching on connective tissue mobility in scleroderma GvDH model

*

Segment A

Segment B

No stretch Stretch

#p<.01 #

Xiong Frontiers Immunol 2017

Page 27: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

What are the effects of NOT stretching?

Page 28: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 29: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Ultrasound measurement methods

Page 30: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Pig growth

Page 31: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Gait analysis

ANOVA effect of hobble p= .03

Page 32: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Ultrasound tissue thickness measurements

ANOVA effect of injury p = .007

Page 33: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Thoracolumbar shear strain measurements

ANOVA main effects of injury p = .027 and hobble p = .021

Page 34: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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

Page 35: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Fear

How would stretching impact this model?

inflammation resolution

improved tissue mobility

acute inflammation

PAIN

decreased

fear of

movement

Page 36: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Effect of stretching on gait velocity in pigs 4 weeks after removing hobbles

ANOVA p<.05

Page 37: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Effect of stretching on thoracolumbar fascia mobility in pigs 4 weeks after removing hobbles

ANOVA p<.05

Page 38: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Why did stretching work in rats but not in pigs?

Page 39: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Why did stretching work in rats but not in pigs?

Page 40: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

Integrative medicine: making new connections

Musculoskeletal system

Immune system

Movement Health

Page 41: Connective Tissue, Stretching, Inflammation and ... UVM IM lecture March 2017.pdf · Connective Tissue, Stretching, Inflammation and Musculoskeletal Pain H E L E N E L A N G E V I

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