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Randomized Controlled Trial
. 2011 Mar;12(3):340-51.
doi: 10.1016/j.jpain.2010.07.011. Epub 2010 Dec 13.

Drug response profiles to experimental pain are opioid and pain modality specific

Lindsay L Kindler  1 , Kimberly T Sibille, Toni L Glover, Roland Staud, Joseph L Riley 3rd, Roger B Fillingim
Affiliations
Randomized Controlled Trial

Drug response profiles to experimental pain are opioid and pain modality specific

Lindsay L Kindler et al. J Pain. 2011 Mar.

Abstract

Given our limited ability to predict analgesic efficacy, further research is needed to understand factors influencing analgesic response patterns. The aim of this study was to better understand the relationship between morphine and butorphanol analgesic efficacy tested against multiple pain modalities within the same individuals. Participants included healthy men (n = 72) and women (n = 67) who underwent thermal, pressure, and ischemic experimental pain testing before and after the double-blind administration of morphine and butorphanol during separate testing sessions. Factor analysis revealed 6 factors with analgesic effects grouped primarily by pain modality and specific to either morphine or butorphanol. Hierarchical cluster analysis of individual factor scores led to 4 distinct drug response profiles. Three groups displayed exceptional analgesic efficacy produced by 1 type of opioid on 1 pain stimulus modality, whereas the fourth drug response profile was characterized by average analgesic efficacy across all pain modalities for both opioids. These findings suggest that opioids with varying efficacy at the μ and κ receptors produce independent effects on unique pain mechanisms and that individual responsiveness for some is dependent on pain mechanism and opioid type, although a subset of the population is moderately responsive to opioids regardless of efficacy of receptor binding or predominant pain mechanism being activated.

Perspective: This investigation provides a foundation for understanding patterns of opioid efficacy in varying types of pain. Our findings suggest that opioid response patterns are more complex than originally thought with about half of individuals exhibiting opioid and pain modality specific analgesic response profiles.

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Figures

Figure 1
Figure 1
Timeline of procedures during experimental drug sessions. The boxed text represents the procedures (white) and rest breaks (gray) implemented during the study session. The bidirectional arrows between thermal pain and pressure pain indicate that these two procedures were conducted in counterbalanced order. Time estimates for each testing procedure are documented below the timeline. Adapted from: Fillingim RB, Ness TJ, Glover TL, Campbell CM, Hastie BA, Price DD, Staud R: Morphine responses and experimental pain: Sex differences in side effects and cardiovascular responses but not analgesia. Journal of Pain 6:116-124, 2005.
Figure 2
Figure 2. Cluster profile across standardized factor scores
* Values reported in this figure are standardized factor scores, consequently a value of 0 is equivalent to the group mean, a value of +1.0 represent 1 (SD) above the mean, and −1.0 represents 1 SD below the mean. BU: butorphanol; MS: morphine; TS: temporal summation; PPT: pressure pain threshold; Th: threshold; Tol: tolerance; ischem.: ischemic
See this image and copyright information in PMC

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