How a research response takes

time to build research of

whiplash
Michele Sterling
BPhty, MPhty, Grad Dip Manip Physio, FACP, PhD
NHMRC Senior Research Fellow
Associate Director, CONROD, UQ

Whiplash: The Problem

Poor health outcomes

Personal and economic costs
Clinically difficult to effectively treat
Other factors: environmental; sociocultural

WHIPLASH

2001........
QTF (1995):
Need more research
Clinical Guidelines (MAA, NSW)

Mostly consensus based

Whiplash: Where to Start ?

What is the recovery pathway like?
What processes underlie WAD ?
What is different about those who recover
and those who dont?
Can we predict those who will not recover?
Does current treatment work?
Can we develop better treatments?
CAN we improve health outcomes and.
reduce costs?

Recovery Pathways
Predicted disability trajectories & predicted probability of membership (%).
70.0
60.0

N=155
Chronic severe (16%)

Group based
trajectory
modeling

Predicted NDI

50.0
40.0
30.0

Moderate 39%)

2-3 months
important

20.0

Mild/recovered
Mild (45%)

10.0
0.0
1

7
8
Month

Sterling, Hendrikz, Kenardy 2010 Pain 150:22-28

10

11

12

13

Processes underlying WAD

Why bother looking? Isnt it just neck pain? Its
just a minor injury
Physical and psychological

Nociceptive (pain) processing

PTSD symptoms and stress responses
Motor/movement deficits
Psychological factors
Recovery expectations
Perceived injustice
Pain catastrophising

WHIPLASH

Different mechanisms seem to underlie

different neck pain conditions

Pressure Pain Thresholds

Cold Pain Thresholds

25

500
400
300
200
100
C2-3

C5-6

median
nerve

radial
nerve

ulnar
nerve

tibialis
anterior

Temperature (C)

Pressure (kPa)

600

20
15
10
5
0
cervical spine

Chronic WAD; NDI 44(12)%

Chronic Idiopathic; NDI 29(16)%
Controls

deltoid

tibialis anterior

Scott, Jull, Sterling 2005 Clin J Pain (21):175-181

Elliott et al Clinical Radiology 2008
Chien, Eliav, Sterling 2009 Manual Therapy

Sensory features predict poor functional

recovery following whiplash injury

PPT
degrees celsius

500

400
350
300
250
200
150
100

Change NPQ

kPa

450

<1

Cold pain
Threshold

23
21
19
17
15
13
11
9
7
5
<1

C5/6, C2/3, Upper limb nerve trunks

Tibialis Anterior
Control

Recovered NDI <8%

Treatment
Milder
pain NDI group
9-29% baselines
Moderate to severe pain NDI 30>%

33.813.3

41.014.1

42.314.4

Sterling et al (2003) Pain 104:509-517

Spinal cord hyperexcitability

Electrical stimulation

EMG biceps femoris

50
45
40
35

mA

30
25
20
15
10
5
0
WAD

Control

Sterling, Curatolo et al (2008) Clin J Pain

msec

Van Oosterwijck J et al, Europ J Pain 2012

Trajectories: PTSD symptoms

Predicted PDS trajectories with 95% confidence limits

Severe

35.0

Predicted PDS

30.0
25.0

Mod/severe

20.0
15.0

Moderate

10.0
5.0
0.0
1

Mild
PDS (40%)
Resilient

7
Month

Recovering (43%)

10

11

12

13

Chronic mod-severe (17%)

Sterling, Hendrikz, Kenardy 2010 Pain 150:22-28

Criteria met for probable PTSD diagnosis

(PDS)
Longitudinal cohort:
3 months: 22.3% (n=35)

Chronic WAD sample:

33/72: 45.8% PTSD

12 months: 17.1% (n= 27)

Sterling, Hendrikz, Kenardy
2010 Pain 150: 22-28

Dunne, Sterling, Kenardy 2012

Clin J Pain (in press)

PTSD symptoms

Other
psychological
factors

Nociceptive
processing

WHIPLASH
Movement/motor
deficits

Processes: Where to from here?

Pain processing mechanisms
fMRI studies
Exploration of descending
pain modulation

Stress system responses

Heart Rate Variability
COMT gene variation
Cortisol

Psychological processes
Beliefs and expectations

Relationships between
physical & psychological
factors

Nerve tissue changes

MRI Studies spinal cord
Inflammatory biomarkers

Modulation of PTSD and

effect on pain
Modulation of pain and
effect on psych
presentation

Can we predict those who dont

recover?

Most consistent predictors:

Initial pain intensity
Initial disability levels

most have been phase 1 (exploratory) studies

Phase 1 study (2000-2004) (Sterling et al, Pain, 2005, 2006)

Initial disability levels

Decreased neck movement
Cold hyperalgesia
PTSD symptoms - IES

Validation of Predictors
Phase 3 Study:
Multicentre international cohort study Brisbane,
Melbourne, Montreal, Reykjavik
n=286
Discrimination analysis
Between no/mild disability vs moderate/severe disability
Predicted
NDI 12
months

Area under
curve ROC

Std error

Significance

95% CI

Original
model

0.85

0.029

< 0.001

0.79 0.91

Validation
model

0.89

0.024

< 0.001

0.84 0.94

Sterling, Hendrikz, et al (2012) Pain 153: 1727-1734

Initial pain
Initial disability
Cold hyperalgesia
Neck movement
Psychological factors
PTSD symptoms
Recovery expectations
Depression
Pain catastrophising

PTSD symptoms

Other
psychological
factors

Cold hyperalgesia
PTSD symptoms
Pain levels
Disability levels

Other factors

Nociceptive
processing

Movement/motor
deficits

WHIPLASH

Does current treatment work?

Strongest evidence for activity/exercise ~ acute and chronic WAD ~ but

effects are modest
Insufficient evidence to support any treatment for sub-acute WAD
Chronic WAD Modest effects at best with rehabilitation (Jull et al 2007,

Stewart et al 2007)

- RFN

WHY not?
Those with sensory hypersensitivity dont do well
with standard rehabilitation.
18
16

RCT in chronic WAD

Change NPQ

14
12

Exercise
program/manual
therapy vs Act as
Usual

10
8
6
4
2
0
Total group

No sensory

mechanical
hperalgesia

Mechanical &
cold
hyperalgesia

Exercise
Treatment booklet/act
group baselines
Information
as usual 33.813.3

10 weeks treatment
pre post follow-up
41.014.1
42.314.4
Jull, Sterling
(2007) Pain

45

25

40

20

35

15
WL

10

TREAT

30

WL
TREAT

25
20
Pre

0
Pre

Post

PTSD symptoms - PDS

Post

6mo

6mo

Pain related disability - NDI

Management of acute whiplash: A randomized controlled

trial of multidisciplinary stratified treatments
(1)

(11)

(111)

medication

Physiotherapy

Psychology

a) NDI <30

Simple
Analgesia

a) No
hyperalgesia

MT + Th Ex

a) IES >26

CBT

b) NDI >30 +
Hyperalgesia

Opioid
Analgesia

b) Reduced
kinaesthesia

Add
proprioceptive
retaining

b) GHQ28
>30

CBT

c) NDI >30 +
Neuropathic
pain

Adjuvant
agents

c) NDI >30 +
hyperalgesia

Pain
management
Delayed MT +
ThEx

Management of acute whiplash: A randomized

controlled trial of multidisciplinary stratified
treatments
Jull, Sterling, Kenardy, Hendrikz,
Cohen, 2012, under review

100

Recovery NDI <8%

90
80

Pragmatic care

Frequency %

70

Usual care

60
50
40
30
20
10
0
Baseline

11 weeks

6 months

12 months

Ongoing Trials
RCT of exercise in chronic WAD (Brisbane &
Sydney) NHMRC, MAIC, MAA
RCT of dry needling & exercise for chronic
WAD (address sensory
hypersensitivity)NHMRC, MAIC, MAA
RCT physios addressing stress responses for
acute WAD (seek funding)

Trials in development
RCT : pre-treating PTSD followed by physio
exercise for chronic WAD
RCT: medication trials.
Propranolol for acute WAD (MS advisor for USA
trial)
Early pain relief, modulation of CNS
hyperexcitability

Internet delivered interventions

PTSD symptoms

Cold hyperalgesia
PTSD symptoms

Other
psychological
factors

Pain levels
Disability levels

Other factors

Nociceptive
processing

Movement/motor
deficits

WHIPLASH

Medications

Physical
Rehabilitation

Psych intervention

Translational Activities
Clinician focussed translation:
Clinical guidelines for WAD

Translational Activities
Clinician focussed translation: Clinical Measures of
Predictors

Clinical Screening Tool

NDI

<30

31-39

Age
<35

>40

Hyperarousal
<6

>35

Predicted:
Recovery

Neither recovered nor

chronic/severe

Predicted Recovery
Sensitivity
NDI <30 and
age <35

.483 (.39.57)

Specificity
.832 (.76.88)

+LR
2.87 (1.914.33)

PPV
70.7 (59-80)

Presence
of all 3
factors

>6

AGE
<35

>35

Predicted:
Chronic/Severe
Predicted Chronicity
Sensitivity Specificity
+LR
.435 (.31.938 (.89- 7.02 (3.81.55)
.96)
12.94)

Ritchie et al , under review

PPV
71.4 (5584)

Translational Activities
Consumer focussed translation:

http://www.som.uq.edu.au/whiplash

Whiplash Research Group

Dr Carrie Ritchie
Dr Rachael Dunne
Ash Pedler
Andrew Popple
Andrew Stone
Helena Motlagh
Amanda Sumner
Sam Maxwell
Ashley Smith
Tze Siong
Gail Durbridge