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The responses to pharmacological challenges and experimental pain in patients with chronic whiplash-associated pain
Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences.
Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Denmark.
Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Denmark.
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2005 (English)In: The Clinical Journal of Pain, ISSN 0749-8047, Vol. 21, no 5, 412-421 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: This study evaluates the analgesic responses to intravenous administration of morphine, lidocaine, and ketamine and their relations to duration of chronic pain after whiplash trauma. In addition, experimental muscle pain sensitivity and its correlation to pain duration and pharmacological responses were assessed.

Methods: Thirty-three patients with diagnosed whiplash-associated disorder grade II in the chronic stage, according to the Quebec classification, were included. The pharmacological evaluation was performed in a randomized, double-blind, cross-over design and consisted of a 30-minute period of intravenous administration of morphine (0.3 mg/kg), lidocaine (5 mg/kg), ketamine (0.3 mg/kg), or placebo (isotonic saline). Intensity ratings of habitual pain on a visual analogue scale were taken before, during, and after the infusion. The patients were classified as nonresponders, placebo-responders, or responders (minimum 50% decrease of pain intensity) of the drugs. Pressure pain thresholds and intramuscular and cutaneous electrical stimulation pain thresholds were measured. The pain intensity during experimental muscle pain by intramuscular hypertonic saline was also recorded. Experimental pain assessments were performed on the lower legs outside the habitual painful area.

Results: Thirty patients completed the study; 2 were placebo responders and 10 were nonresponders. Of 18 responders, there were 15 morphine responders, 11 lidocaine responders, and 14 ketamine responders. In the patients with whiplash-associated disorder duration less than 2 years, 7 responded to morphine, 5 to lidocaine, and 8 to ketamine. In the patients with pain duration longer than 2 years, 8 responded to morphine, 6 to lidocaine, and 6 to ketamine. Thus, no pattern with respect to pain duration was found. Seventeen patients participated in the experimental pain assessment, and no significant differences in the variables of the intramuscular and cutaneous stimulation and intramuscular-induced pain with respect to response to the pharmacological challenges or whiplash-associated disorder duration existed.

Discussion: The pharmacological challenges identified subgroups of patients with chronic whiplash-associated disorder that might be considered before instituting therapeutic interventions or research. However, the pattern of responses to the pharmacological challenges did not show any clear relationships with pain duration or the experimental pain tests.

Place, publisher, year, edition, pages
2005. Vol. 21, no 5, 412-421 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-12919DOI: 10.1097/01.ajp.0000126155.82815.fcOAI: diva2:17395
Available from: 2008-01-30 Created: 2008-01-30 Last updated: 2009-05-25
In thesis
1. Experimental Aspects on Chronic Whiplash-Associated Pain
Open this publication in new window or tab >>Experimental Aspects on Chronic Whiplash-Associated Pain
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: Chronic pain after whiplash trauma (chronic WAD) to the neck is still a common clinical problem in terms of pain management, rehabilitation and insurance claims. In contrast to the increased knowledge concerning mechanisms of chronic pain in general, no clinical guidelines exist concerning assessment, pain control and rehabilitation of patients with chronic WAD.

Aim: The general aim of this thesis was to use experimental techniques to better understand the complex mechanisms underlying chronic pain after whiplash trauma. The specific aims of papers I and II were mainly to use analgesic drugs with different target mechanisms alone or in combinations to assess their effects on pain intensity (VAS). Experimental pain techniques were used in all studies to assess deep tissue sensitivity (electrical, mechanical and chemical stimuli). Paper IV aimed at assessing deep tissue sensitivity to mechanical and chemical stimulation. The aim in paper III was to investigate if biochemical changes in interstitial muscle tissue (trapezius muscle) could be detected in WAD patients.

Materials and Methods: The thesis is based on three different groups of patients with chronic WAD. In paper III and IV two different groups of healthy controls also participated. All patients were initially assessed in the pain and rehabilitation centre. In paper I (30 patients) and II (20 patients) two different techniques of drug challenges were used. In paper I: morphine, ketamine and lidocaine were used as single drugs. In paper II: remifentanil, ketamine and placebo were used in combinations and together with experimental pain assessments. Microdialysis technique was used in paper III (22 patients from study IV and 20 controls). In paper IV (25 patients and 10 controls) a new quantitative method, computerized cuff pressure algometry, was used in combination with intramuscular saline. In all papers, experimental pain techniques for deep tissue assessment (except cutaneous electrical stimulation in paper I) were used in different combinations: intramuscular hypertonic saline infusion, intramuscular electrical stimulation and pressure algometry.

Results and Conclusion: There are multiple mechanisms behind chronic whiplash-associated pain, opioid sensitive neurons, NMDA-receptors and even sodium channels might play a part. A significant share of the patients were pharmacological non-responders to analgesic drugs targeting the main afferent mechanisms involved in pain transmission, this implies activation of different pain processing mechanisms (i.e. enhanced facilitation or changes in the cortical and subcortical neuromatrix). Experimental pain assessments and drug challenges together indicate a state of central hyperexcitability. Ongoing peripheral nociception (paper III), central sensitization and dysregulation of pain from higher levels in the nervous system may interact. These findings are likely to be present early after a trauma, however it is not possible to say whether they are trauma-induced or actually represents pre-morbid variations. Clinical trials with early assessments of the somatosensory system (i.e., using experimental pain) and re-evaluations, early intervention (i.e. rehabilitation) and intensified pain management could give further knowledge.

Place, publisher, year, edition, pages
Linköping University Electronic Press, 2008. 88 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1035
Neck injury, whiplash-associated disorders, chronic pain, central sensitization, pain assessment, drug challenges
National Category
Anesthesiology and Intensive Care
urn:nbn:se:liu:diva-10693 (URN)978-91-85895-19-9 (ISBN)
Public defence
2008-02-22, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Available from: 2008-01-30 Created: 2008-01-30 Last updated: 2015-11-19

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Lemming, DagSörensen, JanGerdle, Björn
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