title: "Managing" the Placebo Effect: The Single-Blind Placebo Lead-in Response in Two Pain Models.
abstract: "Placebo effects" in analgesic medication trials for chronic pain are pervasive; however, little is known regarding mechanisms or factors that may influence the presence or magnitude of these effects. Our objective is to consider elements of the placebo response in the context of two pain models using a "single-blind placebo lead-in" design (SBPLI).
  
  
  
  As part of two pilot drug trials using knee osteoarthritis (KOA) and non-radicular low back pain (LBP) subjects, SBPLI protocols were conducted. We examined whether gender and/or diagnosis affected placebo responses as observed in changes in patient self-reported pain, depressive and pain anxiety symptoms. We also evaluated the placebo response on performance-based tests (stair climbing, range of motion (ROM), sit to stand repetitions, and 6-minute treadmill distance).
  
  
  
  VAS Pain Intensity (Now) values decreased significantly during the SBPLI for the sample as a whole, but the effects appeared stronger among LBP subjects. CES-D short form values (depressive symptoms) did not decrease significantly during the SBPLI for the sample as a whole, but some placebo effects appeared to emerge for women in the KOA group. PASS values (pain anxiety symptoms) decreased significantly, albeit mildly, during the SBPLI for the sample as a whole.Stair Climb (time) revealed no significant SBPLI effects. Bend Forward to Floor (ROM) increased significantly at the end of the SBPLI period for the sample as a whole, but the effects appeared stronger among KOA subjects. Sit to Stand Repetitions increased during the SBPLI for the sample as a whole. Treadmill Distance did not change significantly from Visit 1 to Visit 2; however, a significant Sex difference for the KOA group was found such that women showed greater Treadmill Distance at Visit 2.
  
  
  
  Placebo effects emerged across psychometric and performance-based measures, indicating the pervasiveness of this phenomenon. In this design, diagnostic and (to a lesser extent) gender categories differentials were observed during the placebo period. The SBPLI design may prove not only a robust method in studying the placebo phenomena, but also as a design element to mitigate some aspects of the placebo response in clinical trials.
authors.affiliation: *Rehabilitation Institute of Chicago normanharden3@gmail.com.
authors.forename: R Norman
authors.initials: RN
authors.lastname: Harden
authors.affiliation: *Rehabilitation Institute of Chicago.|Center for Pain Studies.|Department of PM&R, Feinberg School of Medicine, Northwestern University.
authors.forename: Meryem
authors.initials: M
authors.lastname: Saracoglu
authors.affiliation: *Rehabilitation Institute of Chicago.|Center for Pain Studies.
authors.forename: Sara
authors.initials: S
authors.lastname: Connolly
authors.affiliation: *Rehabilitation Institute of Chicago.|Center for Pain Studies.
authors.forename: Amy
authors.initials: A
authors.lastname: Kirsling
authors.affiliation: *Rehabilitation Institute of Chicago.|Center for Pain Studies.
authors.forename: Kelly
authors.initials: K
authors.lastname: Comstock
authors.affiliation: *Rehabilitation Institute of Chicago.|Center for Pain Studies.
authors.forename: Katherine
authors.initials: K
authors.lastname: Khazey
authors.affiliation: *Rehabilitation Institute of Chicago.|Center for Pain Studies.
authors.forename: Trevor
authors.initials: T
authors.lastname: Gerson
authors.affiliation: Rush University, Behavioral Sciences, Chicago, Illinois, USA.
authors.forename: John
authors.initials: J
authors.lastname: Burns
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology; D003521:Cyclopropanes / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000627:therapeutic use; D017116:Low Back Pain / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy; D010147:Pain Measurement; D010865:Pilot Projects; D015990:Placebo Effect; D012107:Research Design; D016037:Single-Blind Method
chemical_list: D000700:Analgesics; D003521:Cyclopropanes; D000078764:Milnacipran; D004091:Hydromorphone
keywords: Chronic Low Back Pain; Osteoarthritis Pain; Pain Modules; Placebo; Single-Blind Placebo Lead-In