Exercise and pain
Walter R. Frontera, MD, PhD
Professor and Chair (Inaugural)
Department of Physical Medicine and Rehabilitation
Vanderbilt University School of Medicine
And
Medical Director of Rehabilitation Services
Vanderbilt University Medical Center
No disclosures
“To be ignorant of motion is to be
ignorant of nature”
“There is perhaps nothing in nature
older than motion”
Knowledge
Base
“Exercise and Pain” in PubMed
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What is the clinical
evidence that exercise is
analgesic?
Forest plots (eight studies, 11 exercise groups)
Exercise and knee OA Ryo Tanaka et al. Clin Rehabil
2013;27:1059-1071
Exercise and knee OA pain
Ryo Tanaka et al. Clin Rehabil
2013;27:1059-1071
Non-weight-bearing strengthening
exercise
Weight-bearing strengthening
exercise
Aerobic exercise
total
Central sensitization
A description CJ Woolf, Pain 2011
Nociceptor inputs can trigger a prolonged but reversible increase in the excitability
and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon
of central sensitization. Central sensitization manifests as pain hypersensitivity,
particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia,
aftersensations, and enhanced temporal summation. It can be readily and rapidly
elicited in human volunteers by diverse experimental noxious conditioning stimuli to
skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in
secondary changes in brain activity that can be detected by electrophysiological or
imaging techniques.
Molecular systems
Effects of Exercise on pain at the molecular level?
• The opiate/endorphin system
• The endo-cannabinoid system
• Inflammation and the toll-like receptor (TLR) 4 system
Exercise reverses hypersensitivy in neuropathic pain – a
rat model (Stagg et al., Anesthesiology 114:940, 2011)
• Exercise training consisted of
running on a 10-lane motor-driven
rodent treadmill
• 5 days per week, for 5 weeks at a
speed of 14–16 m/min and an 8%
grade.
• Duration was increased to 30
min/day over 14 days.
• An electric grid behind the treadmill
was activated with a weak current.
• Mid-brain periaqueductal gray area
Exercise reverses hypersensitivy in neuropathic pain – a
rat model (Stagg et al., Anesthesiology 114:940, 2011)
• Exercise training consisted of
running on a 10-lane motordriven rodent treadmill
• 5 days per week, for 3 or 5
weeks at a speed of 14–16
m/min and an 8% grade).
• Duration was increased to 30
min/day over 14 days.
• 10 m/min (lower intensity) or 16
m/min (higher intensity)
Immobilization, hyperalgesia
and exercise
(Chuganji et al., Neurosci Letters 584:66, 2015)
• Male Wistar rats
• Immobilized right hindlimb by casting
• 3 groups: immobilization,
immobilization and treadmill exercise,
controls
• Exercise: 30 min/day; 5 days/week
• Mechanical sensitivity test, 10 times
with 4- and 15-g von Frey filaments for
paw withdrawal
• beta-endorphin in hypothalamus and
mid-brain periaqueductal gray
Immobilization, hyperalgesia
and exercise
(Chuganji et al., Neurosci Letters 584:66, 2015)
• Male Wistar rats
• Immobilized right hindlimb by casting
• 3 groups: immobilization,
immobilization and treadmill exercise,
controls
• Exercise: 30 min/day; 5 days/week
• Mechanical sensitivity test, 10 times
with 4- and 15-g von Frey filaments for
paw withdrawal
• beta-endorphin in hypothalamus and
mid-brain periaqueductal gray
“The physiological mechanisms explaining endogenous analgesia following exercise …
due to the release of endogenous opioids and activation of the (supra)spinal
nociceptive inhibitory mechanisms orchestrated by the brain. However, aerobic
exercise activates pain facilitation rather than inhibition in some patients with chronic
pain and central sensitization (fibromyalgia, whiplash, and chronic fatigue
syndrome). Exercising local muscle groups results in increased generalized pain
sensitivity in fibromyalgia …”
Endocannabinoid system
(Raichlen et al., EJAP 113:869, 2013)
• Natural system that includes:
– endogenous ligands including anandamide (AEA) and 2-arachidonylglycerol (2AG)
– CB1 and CB2 cannabinoid receptors (receptors activated by THC) present in
brain, muscle, GI tract, liver, adipose tissue, pancreas
• Ligands released by neurons to modulate synaptic activity and plasticity
– Cross blood-brain barrier
• Activation of this system reduces pain
– Linked to stress-induced analgesia
– Changes associated with the use of THC
First evidence that exercise activates endocannabinoid system
(Sparling et al., NeuroReport 14:2209, 2003)
• Trained young subjects
• 45 minutes on treadmill
or bike at 70-85% max
HR
• Significant increases in
runners and cyclists but
not in controls that did
not exercise
Exercise induce increases in eCBs
• Recreationally fit human
runners
• Treadmill exercise at 4
intensities for 30
minutes
• Significant increases
only at moderate
intensities (~70-85%
age-adjusted max HR)
Raichlen et al., EJAP 113:869, 2013
Exercise and endocannabinoids (Heyman et al., Psychoneuroendo 37:844,
2012)
• Healthy trained cyclists
• 60 min at 55% Wmax
followed by 30 min at
75%
• Plasma levels of
endocannabinoids
• Increase in cortisol,
brain-derived
neurotrophic factor, and
endorphins
The importance of genetics
•
Heritability estimate for VO2
max is 47%
•
Variance in exercise behavior
explained by genetics 23% to
71%
•
Variability in response to
training with aerobic training (0
to 100% increase)
The Human Gene Map for Performance and Health-Related Fitness
Phenotypes: The 2005 Update. RANKINEN et al., MSSE 38:1863, 2006.