Preconditioning Effects on Analgia

Price et al. (1999) applied placebo creams and graded levels of heat stimulation on three adjacent cutaneous regions of the forearm, giving subjects expectations that cream A was a strong analgesic, cream B was a weak analgesic, and cream C was a control agent.

Immediately after these conditioning trials, subjects rated their expected pain levels for the placebo test trials wherein the stimulus intensity was the same for all three regions. The conditioning trials led to graded levels of expected pain (C ≥ B ≥ A) for the three creams, as well as graded magnitudes of actual pain (C ≥ B ≥ A) when tested during placebo test trials. Thus, magnitudes of placebo analgesia could be graded across three adjacent skin areas, demonstrating a high degree of somatotopic specificity for placebo analgesia.

Expected pain levels accounted for 25–36% of the variance in post-manipulation pain ratings. In another study (Benedetti et al., 2003b), one group of subjects was pharmacologically preconditioned with ketorolac (a nonopioid analgesic) for 2 days in a row, then the ketorolac was replaced with a placebo on the third day along with verbal suggestions of analgesia.

This procedure induced a strong placebo analgesic response. In order to see whether this response was due to the pharmacological preconditioning, a second group of subjects was also preconditioned with ketorolac, but the placebo was given on the third day along with verbal suggestions that the drug was a hyperalgesic agent.

These verbal instructions were sufficient not only to completely block placebo analgesia, but also to produce hyperalgesia. This study clearly shows that placebo analgesia depends on expectation of a decrease in pain, even though analgesic preconditioning is performed.