Experimental Aspects on Chronic Whiplash Associated Pain

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…


1 Introduction
1.1 Clinical background
1.2 Epidemiology
1.3 Trauma
1.4 Pathogenesis and prognosis
1.5 Treatment
1.6 Classification
1.7 ICF
1.8 Associated muscle pain
1.9 Neurobiology
1.10 Pharmacological challenges
1.11 Pharmacological aspects
Opioids (morphine and remifentanil)
1.12 Experimental pain assessments
1.12.1 Electrical pain
1.12.2 Chemical pain
1.12.3 Mechanical pain
1.13 Microdialysis
2 Aims of the thesis
2.1 Specific aims
3 Subjects
3.1 Paper I
3.2 Paper II
3.3 Paper III
3.4 Paper IV
4 Methods
4.1 Drug infusion (Paper I)
4.2 Drug infusion (Paper II)
4.3 Ketamine concentration (Paper II)
4.4 Electrical stimulation and pain thresholds
Cutaneous (Paper I)
Intramuscular (Papers I and II)
4.5 Manual pressure algometry (Papers I, II and III)
4.6 Saline-induced muscle and referred pain (Papers I, II and IV)
4.7 Computerized cuff pressure algometry (Paper IV)
4.8 Methods of microdialysis (Paper III)
Experimental protocol
4.9 Visual analogue scale (Paper I-IV)
4.10 Reaction time (Paper II)
4.11 Statistical methods
5 Results
5.1 Paper I
5.1.1 VAS ratings five days before and five days after testing
5.1.2 Effect of drug – longitudinal analysis
5.1.3 Effect of drug – comparisons between drugs
5.1.4 Pain duration vs. pharmacological outcome
5.1.5 Responders (≥ 50 % reduction of pain intensity in the neck)
5.1.6 Pain duration vs. pharmacological response
5.1.7 Non-responders
5.1.8 Experimental pain assessments
5.1.9 Pain duration and pharmacological effects vs. experimental pain
5.2 Paper II
5.2.1 Background data
5.2.2 Plasma concentrations
5.2.3 Habitual pain and reaction time
5.2.4 Pressure pain thresholds
5.2.5 Intramuscular electrical stimulation
5.2.6 Intramuscular saline infusion
5.2.7 Side-effects
5.2.8 Multivariate analysis
5.3 Paper III
5.3.1 Algometry (PPT)
5.3.2 Pain intensity (VAS)
5.3.3 Blood flow
5.3.4 Lactate and pyruvate
5.3.5 Potassium (K+)
5.3.6 Interleukin-6 (IL-6)
5.3.7 Glutamate
5.3.8 Serotonin (5-HT)
5.3.9 Regression of group membership
5.3.10 Regression of overall pain intensities in the WAD group
5.3.11 Regression of Pain intensities during exercise
5.4 Paper IV
5.4.1 Habitual pain
5.4.2 Cuff pain threshold
5.4.3 Characteristics during tonic cuff stimulation
5.4.4 Saline induced muscle and referred pain
5.4.5 Correlation between the two pain modalities (AUC vs PVA)
6 Discussion
6.1 Pharmacological challenges
6.1.1 Central sensitization
6.1.2 Target mechanisms
6.1.3 Pharmacological response or non-response
6.1.4 Pharmacology and experimental pain (Paper II)
6.1.5 The impact of duration on pharmacological response (Paper I)
6.2 Experimental pain assessments
(In part also discussed under section 6.1.4)
6.2.1 The impact of duration on experimental pain (Paper I and II)
6.2.2 Manual pressure algometry (Paper III)
6.2.3 Computerized cuff pressure algometry (Paper IV)
6.2.4 Saline-induced muscle and referred pain (Paper I and IV)
6.3 Microdialysis
6.3.1 Serotonin (5-HT)
6.3.2 IL-6
6.3.3 Pyruvate, lactate and blood flow
6.4 Methodological considerations
7 Summary and Conclusion
8 Future prospects

Author: Lemming, Dag

Source: Linköping University

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