Abstract
BackgroundInability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated.Methods/DesignIn this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients’ global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables.DiscussionPharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a “trial and error” fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients.Trial registrationClinicaltrials.gov, NCT01179828
Highlights
Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved
Pharmacotherapy is a mainstay in chronic pain treatment
Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients
Summary
Identifying the best drug in a given patient is a time consuming and frequently frustrating task for all the persons involved. The growing knowledge about pain perception and transmission has led to a new understanding of how chronic pain might be maintained and offers several new targets for therapeutic management Such mechanismbased treatment approaches are given high priority in translational pain research. The combination of phenotyping disturbances in pain processing and genotyping predisposition to pain and polymorphism in drug metabolism may offer the perspective of a more specific treatment of chronic pain. This may lead to a better selection of the therapeutic strategy in individual patients, thereby reducing the likelihood of ineffective treatment and adverse effects. All authors have read and approved the final version of this protocol
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