Effect of sedation on pain perception

Abstract

Background: Sedation or anesthesia is used to facilitate many cases of an estimated 45 million diagnostic and therapeutic medical procedures in the United States. Preclinical studies have called attention to the possibility that sedative-hypnotic drugs can increase pain perception, but whether this observation holds true in humans and whether pain-modulating effects are agent-specific or characteristic of IV sedation in general remain unclear.

Methods: To study this important clinical question, the authors recruited 86 healthy volunteers and randomly assigned them to receive one of three sedative drugs: midazolam, propofol, or dexmedetomidine. The authors asked participants to rate their pain in response to four experimental pain tasks (i.e., cold, heat, ischemic, or electrical pain) before and during moderate sedation.

Results: Midazolam increased cold, heat, and electrical pain perception significantly (10-point pain rating scale change, 0.82 ± 0.29, mean ± SEM). Propofol reduced ischemic pain and dexmedetomidine reduced both cold and ischemic pain significantly (-1.58 ± 0.28, mean ± SEM). The authors observed a gender-by-race interaction for dexmedetomidine. In addition to these drug-specific effects, the authors observed gender effects on pain perception; female subjects rated identical experimental pain stimuli higher than male subjects. The authors also noted race-drug interaction effects for dexmedetomidine, with higher doses of drug needed to sedate Caucasians compared with African Americans.

Conclusions: The results of the authors' study call attention to the fact that IV sedatives may increase pain perception. The effect of sedation on pain perception is agent- and pain type-specific. Knowledge of these effects provides a rational basis for analgesia and sedation to facilitate medical procedures.

Figures

Figure 1

This diagram shows the race and gender categorization within drug groups. The main categories are Midazolam, Propofol, Dexmedetomidine and “Undisclosed History”. Subcategories are organized by race and gender.

Figure 2

The Y-axis represents least square means (LSM) of change in pain rating. Error bars represent the corresponding standard error. The scale of pain ratings ranged from 0 to 10. The panel A shows bar graphs that represent LSM of pain rating changes by drug (X-axis category) and pain type (designated by grey scale color). The panel B shows LSM of pain rating changes (Y-axis) for dexmedetomidine by race and gender (X-axis category) to illustrate the interaction effect only observed within the ischemic pain task. Significant pain rating changes (95% CI does not include 0) are marked with an asterisk.

Figure 3

The figure shows pain self report data by subjects at baseline (without sedation). Blue columns represent male data and pink columns represent female data. The difference was significant for all pain types (heat, cold, electrical, and ischemic).

Figure 4

The figure shows pain self report data by subjects at baseline (without sedation). Grey columns represent data from African American participants (N = 33) and white columns represent data from White participants (N = 45). The difference was significant for all pain categories (heat, cold, electrical, and ischemic). Because of the small counts, other race categories were not included in this illustration.