Pain, motor control & plasticity

in the motor system:

How are they related & is it
relevant for rehabilitation?
Paul Hodges
PhD MedDr DSc BPhty(Hons) FACP
Professor & NHMRC Senior Principal Research Fellow
 Pain & motor control

People in pain move differently

For many (but not all) movement is related to

pain experience

Assumed to be relevant for symptoms and

“optimising” movement/motor control may be
helpful for recovery
 Outline

What is pain?

How does motor control relate to pain?

What does this mean for rehabilitation?

 Outline

What is pain?

How does motor control relate to pain?

What does this mean for rehabilitation?

 What is pain?

Pain is a sensory and emotional

experience….
IASP

Pain is also a multi-system output

that motivates and assists the
individual to get out of a situation
that threatens body tissue
Patrick Wall
Pain is an output
 Pain
motivates
Pain is a multisystem output
 Pain neurobiology
• Pain is a non-linear phenomenon
– Not a simple input-output system
Complex
reasoning &
Pain? emotional
mechanisms

Central
sensitisation

Nociceptive input
Biology Pain neurobiology
• Not all pain is the same
– Nociceptive
• Assumed to be predominantly driven by activation of
peripheral nociceptive fibres Scholz & Woolf, 2002
– Central sensitization
• Amplification of neural signaling within the central nervous
system that elicits pain hypersensitivity – from cellular to
widespread network Woolf 2011
– Neuropathic
• Pain attributable to a lesion or dysfunction in the peripheral or
central nervous system Woolf, 2004
• Different mechanisms - Different treatments
• Overlap
Biology
Pain neurobiology:
Treatment
• Different pain mechanisms require different
approaches
– Nociceptive – reduce/block input
• Modify tissue loading – motor control
• Blocks, etc

– Central sensitisation – reduce amplification

• Psychological targets
• Pharmacological
• Movement and physical activity

– Neuropathic - Target source

• Address mechanical/inflammatory site
• Pharmacological
 Outline

What is pain?

How does motor control relate to pain?

What does this mean for rehabilitation?

PAIN
PAIN
 Suboptimal
tissue loading

Injury

PAIN
 Why don’t all people with a
“suboptimal” strategy end up with
injury/pain?

Load
Tissue
tolerance
threshold
Exposure
(Frequency/duration
of loading)

Dye (1996) Clin Orthop Rel Res

 Excessive force/force
combination
Excessive Sustained
motion force

Excessive
Tissue
Load
muscle
creep
tension

Exposure
Poor (Frequency/duration Poor
coordination of loading) coordination
between Poor control of between
adjacent axis of rotation rotation/translati
segments on
 Suboptimal loading

May explain the onset of injury/pain

But may not be the reason it persists

 Suboptimal
tissue loading

Injury

interference/
PAIN inaccuracy
 Planning & initiation of voluntary
movement (incl. postural components)
Primary
somatosensory cortex Primary motor cortex
Posterior parietal Supplementary motor cortex
cortex Premotor cortex
Prefrontal cortex

Basal ganglia
Vestibular nuclei
Cerebellum Reticular formation

Sensory motor Basic movement

integration & posture
& learning

Muscle
Spinal
Reflex networks
(involuntary
Movement)
 Injury:
Atrophy & reflex inhibition

L3-4 intervertebral disc

lesion

0.8

Proportion peak amplitude

0.6

0.4
Difference between

0 0.2
5
sides (%)

*
10 0
15 Pre 15 min
20 injury post
injury
25

Hodges, Kaigle-Holm, Holm 2006 Spine Hodges et al, 2007 Eur J Neurosci
 Cytokines: Role in Sub-
acute/chronic muscle structural
Growth Factor
change
Ubiquitin-Proteasome
Control Lesion - injured Lesion - uninjured pathway pathway

IGF-1 NFkB

PI3k Foxo3 Foxo1

15 Connective tissue 150

adipose CSA (mm2)
Connective tissue &

Muscle CSA (mm2)

MuRF1 Atrogin-
Muscle Akt1
1
Adipose *
10 * 100
mTOR Ubiquitin
5 50
Muscle atrophy
0 0
Slow-to-fast transition

6 *
Fold difference

Cytokines *
control mean

* Collagen synthesis
4 TNFa
IL-1b Fatty infiltration
2 TGF-b1
TNFa
0 TGF-b1
Control Injured Non-
IL-1b Cytokines
injured
Hodges et al, 2015 Spine
Where do the cytokines come
from?
Where do the cytokines come
from?
Merge - high
M1 macrophages Total macrophages Merge magnification

# #
Control

$
Injured

#
$

Merge - high
M2 macrophages Total macrophages Merge magnification

#
Injured

# $

200µm 100µm
James et al, 2016 submitted
 Where do the cytokines come
from?
Acute phase Injury
Initial lesion Reflex inhibition
Pain Reduced tonic muscle activation

Altered muscle
function

James et al, 2016 submitted

 Where do the cytokines come
from?
Acute phase Injury
Initial lesion Reflex inhibition
Pain Reduced tonic muscle activation

Altered muscle
function

Subacute-early
Muscle fiber transition Increased muscle Sensitization of
chronic phase Slow fibres (3 months);  Fast fibres (6 months) fatigability nociceptors
3 months

6 months M2-M1 transition of muscle Pain

& adipose macrophages

Inflammatory Muscle fibrosis featuring

Increased Increased expression increased collagen
response
adipose of TNF and IL-1β expression
in adipose

James et al, 2016 submitted

 Where do the cytokines come
from?
Acute phase Injury
Initial lesion Reflex inhibition
Pain Reduced tonic muscle activation

Altered muscle
function

Subacute-early
Muscle fiber transition Increased muscle Sensitization of
chronic phase Slow fibres (3 months);  Fast fibres (6 months) fatigability nociceptors
3 months

6 months M2-M1 transition of muscle Pain

& adipose macrophages

Inflammatory Muscle fibrosis featuring

Increased Increased expression increased collagen
response
adipose of TNF and IL-1β expression
in adipose

Chronic Muscle unloading

phase
Beyond 6 Muscle Atrophy
months

James et al, 2016 submitted

Time-dependent multifidus muscle
plasticity: Different mechanisms

Acute Subacute-Early chronic Chronic

Acute inhibitory/ Pro-inflammatory Disuse/ deconditioning
regeneration phase cytokine phase phase
Muscle inhibition Slow-to-fast muscle fiber Muscle/muscle fiber
Acute size reduction transformation atrophy
(?vascular/other mechanism) Fibrosis Fibrosis
Acute adipose activation Fatty infiltration Fatty infiltration
Regeneration pathway
activation

Maximum intervertebral
disc degeneration

1 week 3 months 6 months 9 months 12 months

Hodges et al, 2015 Spine

 Cytokines: Treatment
• Does not simply mean anti-inflammatory
drugs are required!

• Exercise can change macrophages

– Exercise promotes M2 (anti-inflammatory)
– Muscle fibre-type changes micro-environment
• Exercise can change peripheral and central
sensitivity
 Compromised behaviour
1.00
Preamplifier
LBP
Respitrace
0.80 Control
ES TrA
MD RA
MS OE
Flexion OI 0.60
No pa in
Short MF
Foot switch 0.40
TrA
Long MF Onset Onset *
TrA deltoid 0.20
RA OE SM DM
Deltoid OI
TrA OI
Pa in 0.00
Short MF TrA TrA OI OE RA MD MS ES
Saunders & Hodges, 2005
Long MF OI OE

OE

RA
-20 0 20 40 60
RA 80 100 120
EMG onset relative to deltoid (ms)
RA
MacDonald, Moseley,ES Hodges 2009 Pain OE
OI ES
50 ms TrA

-100 0 100

Time (ms)

Hodges & Richardson, 1996 Spine

 Pain:
Motor cortex organisation/excitability
A. Transcranial magnetic B. Paraspinal muscle EMG
stimulation recordings
over scalp grid Motor cortex
(M1)
Are there differences in the motor cortex?

Medulla
Corticospi
Vertex nal tract Spinal
(Cz) cord
LES
DM

Vertex
(Cz)

E. Motor cortical
map

D. MEPs superimposed
over scalp sites C. MEP recorded at each site
 Chronic LBP:
Motor cortex organisation
Are there differences in the motor cortex?

5
4
3
2
4 Arm Flexion 1
Cz 1 2 3 4 5
CoG-lateral (cm)

Healthy
2 LBP

1
r=0.57 p<0.001
0
-100 -50 0 50 100
Relative onset of TrA (ms) Tsao, Galea, Hodges 2008 Brain
 Chronic LBP:
Motor cortex organisation
Vertex
(Cz)
DM – fine wire LES – fine wire
Are there differences in the motor cortex?

Healthy

2 cm
2 cm

Prop. Peak
1.0
0.8
LBP

0.6
0.4
0.2
0
Tsao, Danneels, Hodges (2011) Spine
 Chronic elbow pain:
Motor cortex organisation
Extensor digitorum Extensor carpi radialis brevis
Are there differences in the motor cortex?

Lateral
epicondylalgia

Painfree
control

Schabrun, Hodges, Vicenzino, Jones, Chipchase, (2014) Med Sci Sports Exer
 Chronic elbow pain:
Motor cortex organisation
Extensor digitorum Extensor carpi radialis brevis
Are there differences in the motor cortex?

Lateral
epicondylalgia

Painfree
control

Schabrun, Hodges, Vicenzino, Jones, Chipchase, (2014) Med Sci Sports Exer
 Knee OA:
Motor cortex organisation
Are there differences in the motor cortex?

Knee Knee
Control OA

Shanahan, Hodges, Bennell, Wrigley, Farrell 2008 Arth Res Therapy

 Suboptimal proprioception
• If your nervous system doesn’t know
where you are or how you are moving
 cannot control movement
accurately
Inacurate input
Panjabi 2006

Inaccurate use of input

Brumagne et al. 2004

Different central representation

and integration of input
Flor et al. 1997
 Suboptimal
tissue loading

interference/
PAIN inaccuracy
 Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy
 Real or threatened
nociceptive input/pain/injury
 Real or threatened
nociceptive input/pain/injury

Changes in motor behaviour

Subtle Major
Redistributed activity Avoidance of
within & between muscles movement
 Real or threatened
nociceptive input/pain/injury

Changes in motor behaviour Experience

Subtle Major
Redistributed activity Pain cognition
Avoidance of
within & between muscles movement Pain beliefs
 Real or threatened
nociceptive input/pain/injury

Changes in motor behaviour Experience

Subtle Major
Redistributed activity Pain cognition
Avoidance of
within & between muscles movement Pain beliefs

Changed motor output/mechanical behaviour:

Stiffness, force direction, load distribution,
variability, force & movement amplitude
 Real or threatened
nociceptive input/pain/injury

Changes in motor behaviour Experience

Subtle Major
Redistributed activity Pain cognition
Avoidance of
within & between muscles movement Pain beliefs

Changed motor output/mechanical behaviour:

Stiffness, force direction, load distribution,
variability, force & movement amplitude

Short term benefit:

Protection of the injured/painful region
muscle activity/stress, movement, potential for error
Does the adaptation protect
the painful part?
 Adaptation of trunk muscles to an
acute noxious input:
Does the adaptation to pain protect the painful part?

The overall outcome is “protection”

350
OE
330
RA 310

Stability Index (Nm/rad)

OI 290
*
270
250
*

230
210
190 Front-back
TES
LD 170 Back-front
150
LES
Pre-pain Pain

Hodges, Cholewicki, et al, (2013) Eur J Pain

 Adaptation of trunk muscles to an
acute noxious input:
Does the adaptation to pain protect the painful part?

But the individual solution varies

RA r OE r OI r LD r TES r LES r RA l OE l OI l LD l TES l LES l
S1
S2
S3
S4
S5
S6
S7
S8
S9
S10
S11
S12
S13
S14
S15
S16
S17

Hodges, Cholewicki, et al, (2013) Eur J Pain

Is the interpretation that simple?
 Radial
Side view Clamp deviation

Ulnar
Sensor deviation
Lateral
epicondyle
 Radial
Side view Clamp deviation

Ulnar
Sensor deviation
Lateral
epicondyle

Top view
Clamp Flexion
F
* Baseline
N
variation
# E
Lateral
epicondyle Extension
 Is the movement strategy with
reduced noxious input selected?
Pain reduction: -3

Minimal
Pronation-supination

change in
position –
greater use of
painfree
region

Flexion-extension
 Pan reduction: -3
“Taking action” to
protect
- individual
solutions
Minimal change
in position –
greater use of
painfree region
Pan reduction: -2 Pan reduction: -2.5
Is it really that simple?

Small change in Large change in

position – no use position – no use
of painfree region of painfree region
 “Taking action” to protect
- All achieve pain reduction,
despite no reduction in noxious
stimulation for most
8
7
6
Pain (NRS)

5
4
3
2
Is it really that simple?

1
0
No overall Minor Large Combined
change change change
 Interpretation

In the presence of noxious input –

• “Taking action” to reduce threat leads
to reduced pain
• May not depend on reduced
nociceptive input
• May not reduce tissue load
• Implications for interpretation of
treatment outcome
 Real or threatened
nociceptive input/pain/injury

Changes in motor behaviour Experience

Subtle Major
Redistributed activity Pain cognition
Avoidance of
within & between muscles movement Pain beliefs

Changed motor output/mechanical behaviour:

Stiffness, force direction, load distribution,
variability, force & movement amplitude

Short term benefit:

Protection of the injured/painful region
muscle activity/stress, movement, potential for error

Long term consequence:

Suboptimal tissue loading
 Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy
Is there a long term consequence of adaptation to protect?

Long term consequences

Reduces movement which is Reduced movement
important for dissipation of variability
forces

Performance
-8
-7 r = 0.34
Resultant motion

-6
-5
-4
-3
-2
-1
0
1 Variability
-2 0 2 4 6 8 10 12
Preparatory motion

Increases joint
loading
 Delayed “offset” of trunk muscle
Is there a long term consequence of adaptation to protect?

activity predicts future LBP

N=292 college athletes

Episode of LBP
Longer delay: 77 [36] vs. 63 [31] ms
Fewer muscles off: 0.8[1] vs. 1.3[1.1]

Odds of low back pain  3% for

each 1 ms delay

Cholewicki et al., 2005 Spine

 Is there a cost? Medial knee muscle co-
Is there a long term consequence of adaptation to protect?
there

contraction increases knee OA progression

Medial tibial annual cartilage

10
volume change

-5

-10
10 20 30 40 50 60

Hodges, Bennell, Wrigley, van den Hoorn, (2015) Man Ther

 Interpretation
• Motor adaptation may provide short
term benefit, but with long term
consequences if not resolved
– Pain motivates adaptation, reduction of
pain
– Adaptation might contribute to
Is it really that simple?

persistence of pain
– Development of secondary issues
 Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy

Conditioned
pain response
 Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy

Conditioned
pain response
 Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy

Conditioned
pain response
 How are movement and
acute pain related

• Motor response assists the individual to

get out of a situation that threatens
body tissue
 How are movement and
chronic pain related

• Chronic pain serves no benefit to the

individual
• Threat to tissues may be resolved
• Nociceptive input may continue +
peripheral and central sensitization
• Motor response may be
– Excessive, Prolonged, Irrelevant
– Part of the problem
 Why does pain persist?

No
Ongoing
ongoing
threat to
Bio- threat to
tissues
tissues

Psycho- Social
 Outline

What is pain?

How does motor control relate to pain?

What does this mean for rehabilitation?

Do we need to treat the “body”
or just the “mind” in back pain?
 Is the “body” relevant in
“musculoskeletal” pain?

Educatiion;
Motor control
behavioural
approach
therapy

Nociceptive Central
input changes
Biology Treatment by pain “type”

Nociceptive pain Central pain Neuropathic pain

Detailed assessment of Detailed assessment Detailed assessment

strategy of suboptimal of pain cognitions, of neurodynamics,
tissue loading: Posture, psychosocial features, nerve loading
Movement, Muscle function, goals for peripheral
activity, and Sensation neuropathic pain

• Individually tailored pain

• Individually tailored motor
education • If peripheral nerve
control training program
• Targeted psychological involvement - Individually
• Optimise tissue
program tailored
loading
• Fear conditioning neurodynamic/motor
• Other interventions to
• Pain coping skills control program to change
enable change in
• Acceptance nerve loading
biomechanics
• etc • Other treatments as per
• Manual therapy
• Graded activity Central pain
• etc
• Social intervention
 Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy

Conditioned
pain response
 Tx: Change motor
control to optimize
loading

Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy

Conditioned
pain response
 If load on tissues (potentially
sensitized) causes nociceptor discharge
which contributes to the pain
experience

Then it may be helpful to change

motor control to optimise load on tissues
 Outcomes of treatment
• Improved structure & behaviour of deep trunk
muscles
Suboptimal Suboptimal Suboptimal
(Hides et al. 2001; Tsao et al. 2008)
muscle
• Reduced activity of superficial trunk muscles
sensory muscle
activity function activity
(Tsao, Druit & Hodges, 2010)
• Improved
(Compromised proprioception (Augmented
activity) activity)
(Falla, Jull & Hodges, 2007)
• Improved spine posture
(Falla, Jull & Hodges, 2007)
• Improved movement
Suboptimal Suboptimal
(Scholtes et al, 2010)
posture movement
 Effect of treatment
Pregnancy-related
pelvic pain
↓ pain & disability
Stuge et al 2003

Acute unilateral LBP

↓ LBP recurrence
Hides et al, 2001

Spondylolisthesis
pain & disability
O’Sullivan et al 1997
 Effect of treatment
More effective for specific LBP phenotypes
Pregnancy-related Chronic non-specific LBP
pelvic pain ↓ pain & disability & better
↓ pain & disability early vs. graded exercise
Stuge et al 2003 Ferreira et al, 2007

Acute unilateral LBP Chronic non-specific LBP

↓ LBP recurrence no additional benefit
Hides et al, 2001 Cairns et al, 2006

Spondylolisthesis Chronic non-specific LBP

pain & disability no additional benefit
O’Sullivan et al 1997 Koumantakis et al, 2005
Biology
Motor control:
Treatment
• Different motor control presentations require
different approaches

– Address individual specific loading strategy –

muscle activation, alignment, movement
 Tx: Change motor
control to optimize
loading

Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy
Tx:  inter-
ference
Counteract
effects

Conditioned
pain response
 Tx: Change motor
control to optimize
loading

Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy
Tx:  inter-
Tx: Reduce ference
excessive Counteract
protection effects

Conditioned
pain response
 Tx: Change motor
control to optimize
loading

Suboptimal
tissue loading

Protective interference/
response PAIN inaccuracy
Tx:  inter-
Tx: Reduce ference
excessive Counteract
protection effects

Conditioned
pain response

Tx: Extinguish
conditioning
Psych-
Social
Psychology & Social:
ology
Treatment
• Different psychological presentations
require different approaches

• Different social features require

different approaches

• Specificity in all domains

 Key messages
Pain and motor control interact in multiple
dimensions

Motor control in pain may have positive and

negative implications

Persistent pain – nociceptive input may still be

relevant, but not necessarily

Motor control can be changed with positive

clinical outcomes

Relevance of interventions to change motor

control depend on the individual
Program Grant Team UQ Collaborators A/Prof Thomas Graven-Nielsen, Centre for
Prof Bill Vicenzino Prof Gwen Jull Sensorimotor Interac on, Aalborg, Denmark
Prof Kim Bennell A/Prof Sandy Brauer
Prof David Hunter Dr Kylie Tucker Prof Alf Thorstensson, Karolinska Ins tutet,
Dr Andrew Claus Stockholm, Sweden
Post-docs Dr Michelle Smith
A/Prof Jacek Cholewicki, Yale University, New Haven,
Dr Natalie Collins Doctoral students (Past) CT, USA
Dr Welber Marinovic Andrew Briggs
Dr Mary Massery
Dr Sauro Salomoni Angela Chang
Dr Ryan Stafford Andrew Chapman Chicago USA
Dr Ruth Sapsford Andrew Claus Dr Paul Cordo, Dr Fay Horak, Oregon Health Sciences
A/Prof Francois Hug Sallie Cowan University, Portland, OR, USA
Dr Rachel Park Anna Dawson Prof Victor Gurfinkel, Russian Ins tute of Informa on
Janine Gray Transmission Problems, Moscow, Russia
Research staff Allison Greig
Wolbert van den Hoorn Leanne Hall Prof Sten Holm & Dr Allison Kaigle, Sahlgrenska
Markus Kiel Nick Karayannis University Hospital, Göteborg, Sweden
Greg James Jo Knox
Mandy Nielsen Linda-Joy Lee Dr Anne Mannion, Schultes Klinik, Zurich Switzerland
Glenn Russell David Macdonald
Rebecca Mellor Prof Jaap van Dieen, Vrije University, Amsterdam,
Doctoral students (Present) Nicola Mok Netherlands
Kim Allison Lorimer Moseley
Rafeef Aljuraifani Rachel Park Dr Paulo Ferreira, Dr Manuela Ferreira, Universidade
Michael Bergin Peter Poortvliet Federal de Minas Gerais, Belo HorizonteBrazil
Catharina Bexander Ruth Sapsford
Edith Elgueta-Cancino Ryan Stafford
Prof. Shinn-Zong Lin, Tzu Chi University, Taiwan
Alessio Gallina Steven Saunders
Jan Gildea Annina Schmid
Prof Lieven Dannees, Gent University, Belgium
Luke Heales Michelle Smith
David Klyne Natalie Spearing Prof Simon Brumagne & Prof Sabine Verschueren,
Liam Maclachlan Ryan Stafford University of Leuven, Belgium
Laura Morrison Narelle Stubbs
Camille Shanahan Henry Tsao A/Prof Francois Hug, Nantes University, France
Viana Vuvan Donna Urquhart
Peter Window Richard Yang
Prof Jayne Garland, Uni. Bri sh Columbia
Prof Simon Gandevia, Dr Jane Butler, NeuRA, Sydney
Prof Chris Maher, Prof Chris Li le, Sydney University Prof Laurent Bouyer, Uni Laval, Quebec, Canada
Dr Siobhan Schabrun, Prof Lucy Chipchase, Uni Western Sydney
Prof Lorimer Moseley, Uni South Australia
Prof Michele Sterling, Griffith Uni, Gold Coast Dr Janine Gray, University of Cape Town, South Africa
Acknowledgements

@paulwhodges