Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
Implications
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.
Conflict of interest
Conflict of interest statement: None.
Acknowledgements
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
| Placebores | Placebo responders |
| ActiveResp | Active responders |
| Nonglobal | Non responders |
| WADduratio | Duration of pain |
| BasePaini | Baseline pain intensity |
| BaseUnplea | Baseline pain unpleasantness |
| CSQ43 | Coping Strategies Questionnaire/perceived control of pain |
| CSQ44 | CSQ/ability to minimize pain |
| CSQDA | CSQ Diverting attention |
| CSQRS | CSQ Reinterpreting pain sensations |
| CSQ_CSS | CSQ Coping self-statements |
| CSQ_IS | CSQ Ignoring pain sensations |
| CSQ_PH | CSQ Praying and hoping |
| CSQ_CAT | CSQ Catastrophizing |
| CSQJBA | CSQ Increased Behavioural activities |
| BDIindex | Beck Depression Inventory index |
| LSQ01_life | Life Satisfaction Checklist (LiSat-11) Satisfaction with life as a whole |
| LSQ02_work | LiSat-11 Satisfaction with vocational situation |
| LSQP3_econ | LiSat-11 Satisfaction with financial situation |
| LSQ04_leis | LiSat-11 Satisfaction with leisure situation |
| LSQ05_frie | LiSat-11 Satisfaction with contacts with friends and acquaintances |
| LSQ06_sexl | LiSat-11 Satisfaction with sexual life |
| LSQ07_ADL | LiSat-11 Satisfaction with Activities of Daily Life |
| LSQ08_fami | LiSat-11 Satisfaction with family life |
| LSQ09_marr | LiSat-11 Satisfaction with partnership |
| LSQ10_phys | LiSat-11 Satisfaction with physical health |
| LSQ11_psyc | LiSat-11 Satisfaction with mental health |
| MPI1a | Multidimensional Pain Inventory (MPI) Pain severity |
| MPI1b | MPI Interference - pain related interference in everyday life |
| MPI1c | MPI Perceived Life Control |
| MPI1d | MPI Affective Distress |
| MPI1e | MPI Social Support - perceived support from spouse of significant others |
| MPI2a | MPI Punishing Responses |
| MPI2b | MPI Solicitous Responses |
| MPI2c | MPI Distracting Responses |
| MPIGA | MPI General Activity Index |
| EQ5D1_mob | EuroQol mobility |
| EQ5D2_ADL | EuroQol self-care |
| EQ5D3_acti | EuroQol usual activities |
| EQ5D4_pain | EuroQol pain/discomfort |
| EQ5D5_anx | EuroQol anxiety/depression |
| EQ5D7VAS | EuroQol VAS - self estimation of perceived health |
| SF36_PF | SF36 Physical functioning |
| SF36_RP | SF36 Role limitations due to physical pain |
| SF36_BP | SF36 Bodily pain |
| SF36_GH | SF36 General Health |
| SF36_VT | SF36 Vitality |
| SF36_SF | SF36 Social functioning |
| SF36_RE | SF36 Role limitations due to emotional problems |
| SF36_MH | SF36 Mental health |
| SF36_pcs | SF36 Physical score |
| SF36_mcs | SF36 Mental score |
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