Clinical and human experimental pain studies often include so-called “healthy” controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered “healthy” vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors.
aDivision of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Germany
bDepartment of Neurology, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany
cDepartment of Pain Medicine, BG University Hospital Bergmannsheil GmbH, Ruhr-University Bochum, Bochum, Germany
dINSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Boulogne-Billancourt, France
eUniversité Versailles-Saint-Quentin, Versailles, France
fDepartment Neurology and Psychiatry, Sapienza University, Roma, Italy
gDepartment of Neurology and Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark
hDepartment of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
iEtera Mutual Pension Insurance Company, Helsinki, Finland
jDepartment of Pain Management and Research, Oslo University Hospital, Oslo, Norway
kDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
lDepartment of Anaesthesiology, Critical Care Medicine, Pain Therapy & Palliative Care, Pain Center Lake Starnberg, Benedictus Hospital, Tutzing, Germany
mNeuroscience Discovery Research, Eli Lilly and Company, Indianapolis, IN, USA
nPain Research, Department of Surgery and Cancer, Imperial College, London, United Kingdom
oH. Lundbeck A/S, Copenhagen, Denmark
pDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
qDepartment of Neurology, Odense University Hospital, Odense, Denmark
rNeuroscience Technologies, Barcelona, Spain
sDepartment of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
tChair of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim CBTM, Medical Faculty Mannheim, Heidelberg University, Germany (T. Mainka is now with the Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany)
Corresponding author. Address: Department of Neurology, BG University Hospital Bergmannsheil GmbH, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. Tel.: 0049-234-302-3402; fax: 0049-302-6888. E-mail address: firstname.lastname@example.org (E. K. Enax-Krumova)
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
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The EUROPAIN consortium: http://www.imieuropain.org/consortium/. The NEUROPAIN consortium: N. Attal, R. Baron, D. Bouhassira, G. Cruccu, R. Freynhagen, M. Haanpää, P. Hansson, T. S. Jensen, C. Maier, A. Rice, J. Serra, R.-D. Treede, and T. Tölle.
Received January 17, 2015
Received in revised form May 04, 2015
Accepted May 05, 2015