title: Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain.
abstract: BACKGROUND
  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. 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
  In 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.
  
  
  CONCLUSIONS
  Pharmacotherapy 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.
  
  
  BACKGROUND
  Clinicaltrials.gov, NCT01179828.
authors.affiliation: Chronic Pain Management, Lindenhof Hospital, Lindenhof Group Bern, Bern, Switzerland. andreas.siegenthaler@lindenhofgruppe.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Siegenthaler
authors.affiliation: University Department of Anesthesiology and Pain Therapy, Inselspital Bern, Bern, Switzerland. juerg.schliessbach@insel.ch.
authors.forename: Jürg
authors.initials: J
authors.lastname: Schliessbach
authors.affiliation: University Department of Anesthesiology and Pain Therapy, Inselspital Bern, Bern, Switzerland. pascal.vuilleumier@insel.ch.
authors.forename: Pascal H
authors.initials: PH
authors.lastname: Vuilleumier
authors.affiliation: Institute of General Practice BIHAM, Faculty of Medicine, University of Bern, Bern, Switzerland. peter.juni@biham.unibe.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Juni
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. zeilhofer@pharma.uzh.ch.
authors.forename: Hanns U
authors.initials: HU
authors.lastname: Zeilhofer
authors.affiliation: Centre of Sensory Motor Interaction, University of Aalborg, Aalborg, Denmark. lan@hst.aau.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.affiliation: Centre of Sensory Motor Interaction, University of Aalborg, Aalborg, Denmark. curatolo@uw.edu.com.|Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA. curatolo@uw.edu.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Curatolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D059350:Chronic Pain / Q000188:drug therapy / Q000235:genetics; D002985:Clinical Protocols; D000078306:Clobazam; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use; D017116:Low Back Pain / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000627:therapeutic use; D010147:Pain Measurement / Q000379:methods; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D000700:Analgesics; D001569:Benzodiazepines; D000078306:Clobazam; D010098:Oxycodone; D007099:Imipramine