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Whiplash Associated Disorders (WAD): Responses to pharmacological challenges and psychometric tests

  • Mats Persson EMAIL logo , Jan Sörensen and Björn Gerdle



The present study challenges chronic Whiplash Associated Disorders (WAD)-subjects to a pharmacological intravenous (i.v.) test with morphine, ketamine, and active placebo (midazolam). The aim was to describe the short-term responses to drugs and the assumed heterogeneity in the patterns of responses. We related the different responder groups to the results from psychometric tests.


The study includes 95 patients, all with chronic WAD and referred to our departments. They answered a questionnaire including the following psychometric instruments relevant for chronic pain: Beck Depression Inventory, Coping Strategies Questionnaire, Multidimensional Pain Inventory, Life Satisfaction Checklist, SF36 and EuroQol. The subjects also went through sessions with separate infusions of morphine (0.3 mg/kg), ketamine (0.3 mg/kg) and midazolam (0.05 mg/kg). Infusion time was 30 min followed by a 2-h post-infusion assessment. Assessments were made using a Visual Analogue Scale (VAS) for pain intensity and unpleasantness and by statements of per cent pain relieved. A categorical pain rating scale was also used. A positive response was defined as ≥50% decrease of the VAS-level on two consecutive assessment points during the test sessions, anything less was a non response. The placebo responders were defined as those with a positive response to the active placebo infusion.


The tests were completed by 94 subjects and 26% of these were placebo responders. Among the placebo non responders, 47% responded to morphine, 41% to ketamine, 25% to both drugs and 37% to neither morphine nor ketamine (pain intensity assessments). Similar proportions were found in the assessments of pain unpleasantness and per cent pain relieved. Approximately one in four subjects (27%, pain intensity assessment) did not respond to any of the drugs tested. This relatively high proportion of non responders seemed to be worst cases in some aspects of the psychometric tests. Generally, this non responder group had a trend to score worse for most items in the psychometric tests with some reaching significance in a univariate analysis. This result was confirmed in a multivariate context, although the results indicated only small differences between the groups. All three substances showed significant pain relief compared to baseline on all assessment points. On most variables, morphine and ketamine were significantly more effective compared to the active placebo.


There are different subgroups among subjects with chronic WAD with variations in responses to i.v. morphine, ketamine, and midazolam (active placebo). Subjects with chronic WAD who did not respond to any of the drugs tested scored badly in some aspects of the psychometric instruments.


The present study confirms one aspect of the heterogeneity in the population with chronic WAD. The study does not elucidate precise pain mechanisms but taken together with other studies exploring other aspects, it stresses the importance of individualizing the assessment and treatment of subjects with chronic WAD. A common clinical experience is that depression, anxiety and maladaptive coping strategies often are obstacles for successful medical treatment of chronic pain. The present study supports this experience and emphasizes the need for assessment of psychometric variables when planning the treatment of chronic WAD.

DOI of refers to article: 10.1016/j.sjpain.2012.02.008.

Clinical Department of Operation and Intensive Care, Pain Unit, County Hospital Ryhov, SE-551 85 Jönköping, Sweden. Tel.: +46 (0) 36325050; fax: +46 (0) 36325055.

  1. Conflict of interest

    Conflict of interest statement: None.


This study was supported by the Medical Research Council of Southeast Sweden. We wish to express our thanks to the pain nurses, study nurses, and assistant nurses and to the logistic personnel in our institutions – without them there had been no study.

Appendix A. Abbreviations of Fig. 1a and b

PlaceboresPlacebo responders
ActiveRespActive responders
NonglobalNon responders
WADduratioDuration of pain
BasePainiBaseline pain intensity
BaseUnpleaBaseline pain unpleasantness
CSQ43Coping Strategies Questionnaire/perceived control of pain
CSQ44CSQ/ability to minimize pain
CSQDACSQ Diverting attention
CSQRSCSQ Reinterpreting pain sensations
CSQ_CSSCSQ Coping self-statements
CSQ_ISCSQ Ignoring pain sensations
CSQ_PHCSQ Praying and hoping
CSQ_CATCSQ Catastrophizing
CSQJBACSQ Increased Behavioural activities
BDIindexBeck Depression Inventory index
LSQ01_lifeLife Satisfaction Checklist (LiSat-11) Satisfaction with life as a whole
LSQ02_workLiSat-11 Satisfaction with vocational situation
LSQP3_econLiSat-11 Satisfaction with financial situation
LSQ04_leisLiSat-11 Satisfaction with leisure situation
LSQ05_frieLiSat-11 Satisfaction with contacts with friends and acquaintances
LSQ06_sexlLiSat-11 Satisfaction with sexual life
LSQ07_ADLLiSat-11 Satisfaction with Activities of Daily Life
LSQ08_famiLiSat-11 Satisfaction with family life
LSQ09_marrLiSat-11 Satisfaction with partnership
LSQ10_physLiSat-11 Satisfaction with physical health
LSQ11_psycLiSat-11 Satisfaction with mental health
MPI1aMultidimensional Pain Inventory (MPI) Pain severity
MPI1bMPI Interference - pain related interference in everyday life
MPI1cMPI Perceived Life Control
MPI1dMPI Affective Distress
MPI1eMPI Social Support - perceived support from spouse of significant others
MPI2aMPI Punishing Responses
MPI2bMPI Solicitous Responses
MPI2cMPI Distracting Responses
MPIGAMPI General Activity Index
EQ5D1_mobEuroQol mobility
EQ5D2_ADLEuroQol self-care
EQ5D3_actiEuroQol usual activities
EQ5D4_painEuroQol pain/discomfort
EQ5D5_anxEuroQol anxiety/depression
EQ5D7VASEuroQol VAS - self estimation of perceived health
SF36_PFSF36 Physical functioning
SF36_RPSF36 Role limitations due to physical pain
SF36_BPSF36 Bodily pain
SF36_GHSF36 General Health
SF36_VTSF36 Vitality
SF36_SFSF36 Social functioning
SF36_RESF36 Role limitations due to emotional problems
SF36_MHSF36 Mental health
SF36_pcsSF36 Physical score
SF36_mcsSF36 Mental score


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Received: 2011-08-13
Revised: 2012-01-09
Accepted: 2012-01-30
Published Online: 2012-07-01
Published in Print: 2012-07-01

© 2012 Scandinavian Association for the Study of Pain

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