how a research response takes time to build whiplash michele sterling achrf 2012

7/17/2019 How a Research Response Takes Time to Build Whiplash Michele Sterling ACHRF 2012

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Michele Sterling

BPhty, MPhty, Grad Dip Manip Physio, FACP, PhD

NHMRC Senior Research FellowAssociate Director, CONROD, UQ

How a research response takes

time to build – research ofwhiplash



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 don’t?

• 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?



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

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

1 2 3 4 5 6 7 8 9 10 11 12 13Month

P r e d i c t e d N D I

Mild (45%)

Moderate 39%)

Chronic severe (16%)

Predicted disability trajectories & predicted probability of membership (%).

N=155

Group basedtrajectory

modeling

Recovery Pathways

2-3 months

important

Mild/recovered



Processes underlying WAD

• Why bother looking? Isn’t 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 underliedifferent neck pain conditions

100

200

300

400

500

600

C2-3 C5-6 mediannerve

radialnerve

ulnarnerve

tibialisanterior

P r e s s u r e ( k P a )

Pressure Pain Thresholds Cold Pain Thresholds

0

5

10

15

20

25

cervical spine deltoid tibialis anterior

T e m p e r a t u r e ( ° C )

Sc o tt, Jull, Ste rling 2005 C lin J Pa in (21) :175-181

Elliott et a l Clinic a l Ra d iolog y 2008

Ch ien, Elia v, Sterling 2009 M a nua l The ra p y

Chronic WAD; NDI 44(12)%

Chronic Idiopathic; NDI 29(16)%

Controls



Sensory features predict poor functionalrecovery following whiplash injury

C h a n g e N P Q

Treatment group baselines 33.8±13.3 41.0±14.1 42.3±14.4

100

150

200

250

300

350

400

450

500

<1 2 3 6

k P a

Control

Recovered NDI <8%

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

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

Tibialis Anterior

PPT

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

5

7

9

11

13

15

17

19

21

23

<1 2 3 6

d e g r e e s

c e l s i u s

Cold pain

Threshold



Spinal cord hyperexcitability

msec

Electrical stimulation

EMG biceps femoris

Sterling, Curatolo et al (2008) C lin J Pa in

0

5

10

15

20

25

30

35

40

45

50

WAD Control

m A



Van Oosterwijck J et al, Europ J Pain 2012



Trajectories: PTSD symptoms

Predicted PDS trajector ies with 95% confidence limits

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

1 2 3 4 5 6 7 8 9 10 11 12 13Month

P r e d i c t e d

P D S

Mild PDS (40%) Recovering (43%) Chronic mod-severe (17%)Resilient

Severe

Mod/severe

Moderate

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



Criteria met for probable PTSD diagnosis

(PDS)

Longitudinal cohort:

3 months: 22.3% (n=35)

12 months: 17.1% (n= 27)

Sterling, Hendrikz, Kenardy

2010 Pain 150: 22-28

Chronic WAD sample:

33/72: 45.8% PTSD

Dunne, Sterling, Kenardy 2012

Clin J Pain (in press)



WHIPLASH

Nociceptive

processing

PTSD symptoms

Other

psychological

factors

Movement/motor

deficits



Processes: Where to from here?

Pain processing mechanisms

• fMRI studies

• Exploration of descendingpain modulation

Psychological processes

• Beliefs and expectations

Nerve tissue changes

• MRI Studies spinal cord

Inflammatory biomarkers

Stress system responses• Heart Rate Variability•COMT gene variation• Cortisol

Relationships betweenphysical & psychologicalfactors

• Modulation of PTSD and

effect on pain

• Modulation of pain andeffect on psychpresentation



Can we predict those who don’trecover?

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 PredictorsPhase 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

Originalmodel

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



WHIPLASH

Nociceptive

processing

PTSD symptoms

Other

psychological

factors

Movement/motor

deficits

Pain levelsDisability levels

Cold hyperalgesia

PTSD symptoms

Other factors



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



• Those with sensory hypersensitivity don’t do wellwith standard rehabilitation.

0

2

4

6

8

10

12

14

16

18

Total group No sensory mechanical

hperalgesia

Mechanical &

cold

hyperalgesia

C h a n g e N P Q

Treatment group baselines 33.8±13.3 41.0±14.1 42.3±14.4Jull, Sterling (2007) Pain

• RCT in chronic WAD

• Exercise

program/manual

therapy vs Act as

Usual

• 10 weeks treatment

• pre – post follow-upExercise

Information booklet/act as usual

WHY not?



0

5

10

15

20

25

Pre Post 6mo

WL

TREAT

20

25

30

35

40

45

Pre Post 6mo

WL

TREAT

PTSD symptoms - PDS Pain related disability - NDI



Pain

management

Delayed MT +

ThEx

c) NDI >30 +

hyperalgesia

Adjuvant

agents

c) NDI >30 +

Neuropathic

pain

CBTb) GHQ28

>30

Add

proprioceptive

retaining

b) Reduced

kinaesthesia

Opioid

Analgesia

b) NDI >30 +

Hyperalgesia

CBTa) IES >26MT + Th Exa) No

hyperalgesia

Simple

Analgesia

a) NDI <30

PsychologyPhysiotherapymedication

(111)(11)(1)

Management of acute whiplash: A randomized controlledtrial of multidisciplinary stratified treatments



0

10

20

30

40

50

60

70

8090

100

Baseline 11 weeks 6 months 12 months

F r e q u e n c y %

Recovery NDI <8%

Pragma tic care

Usual care

Management of acute whiplash: A randomizedcontrolled trial of multidisciplinary stratified

treatments

Jull, Sterling, Kenardy, Hendrikz,

Cohen, 2012, under review



Ongoing Trials

• RCT of exercise in chronic WAD (Brisbane &Sydney) NHMRC, MAIC, MAA

• RCT of dry needling & exercise for chronicWAD (address sensoryhypersensitivity)NHMRC, MAIC, MAA

• RCT – physios addressing stress responses foracute WAD (seek funding)



Trials in development

RCT : pre-treating PTSD followed by physioexercise for chronic WAD

RCT: medication trials.• Propranolol for acute WAD (MS advisor for USA

trial)

• Early pain relief, modulation of CNShyperexcitability

Internet delivered interventions



WHIPLASHNociceptive

processing

PTSD symptoms

Other

psychologicalfactors

Movement/motor

deficits

Pain levelsDisability levels

Cold hyperalgesia

PTSD symptoms

Other factors

Physical

Rehabilitation Psych interventioMedications



Translational Activities

Clinician focussed translation:

Clinical guidelines for WAD



Translational ActivitiesClinician focussed translation: Clinical Measures of

Predictors



NDI

>40<30 31-39

>6

HyperarousalAGE

Age

>35

<35 >35

<6<35

>4031-39<30

Predicted:Chronic/Severe

Predicted:

Recovery

Neither recovered nor

chronic/severe

Clinical Screening Tool

Predicted Chronicity

Sensitivity Specificity +LR PPV

Presence

of all 3

factors

.435 (.31-

.55)

.938 (.89-

.96)

7.02 (3.81-

12.94)

71.4 (55-

84)

Predicted Recovery

Sensitivity Specificity +LR PPV

NDI <30 and

age <35

.483 (.39-

.57)

.832 (.76-

.88)

2.87 (1.91-

4.33)

70.7 (59-80)

Ritchie et al , under review



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 StoneHelena Motlagh

Amanda Sumner

Sam Maxwell

Ashley Smith

Tze Siong

Gail Durbridge

how a research response takes time to build whiplash michele sterling achrf 2012

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