Efficacy of open-label counterconditioning for reducing nocebo effects on pressure pain

Abstract

Nocebo effects can adversely affect the experience of physical symptoms, such as pain and itch. Nocebo effects on itch and pain have shown to be induced by conditioning with thermal heat stimuli and reduced by counterconditioning. However, open-label counterconditioning, in which participants are informed about the placebo content of the treatment, has not been investigated, while this can be highly relevant for clinical practice. Furthermore, (open-label) conditioning and counterconditioning has not been investigated for pain modalities relevant to musculoskeletal disorders, such as pressure pain. In a randomized controlled trial, we investigated in 110 healthy female participants whether nocebo effects on pressure pain combined with open-label verbal suggestions can be 1) induced via conditioning and 2) reduced via counterconditioning. Participants were allocated to either a nocebo or sham conditioning group. Next, the nocebo group was allocated to either counterconditioning, extinction, or continued nocebo conditioning; sham conditioning was followed by placebo conditioning. Nocebo effects were significantly larger after nocebo conditioning than sham conditioning (d = 1.27). Subsequently, a larger reduction of the nocebo effect was found after counterconditioning than after extinction (d = .99) and continued nocebo conditioning (d = 1.63), with effects similar to placebo conditioning (following sham conditioning). These results show that (counter)conditioning combined with open-label suggestions can modulate nocebo effects on pressure pain, which provides promise in designing learning-based treatments to reduce nocebo effects in patients with chronic pain disorders, particularly for musculoskeletal disorders.

Counterconditioning as Treatment to Reduce Nocebo Effects in Persistent Physical Symptoms: Treatment Protocol and Study Design

“…While studies comparing efficacy of extinction and counterconditioning for reducing nocebo effects are scarce, they consistently showed counterconditioning to be superior to extinction, as counterconditioning can even reverse nocebo effects into placebo effects ( Bartels et al, 2017 ; Thomaidou et al, 2020 ). This finding is also supported by a recent preprint paper ( Meijer et al, 2021 ). Although these studies are promising, only healthy participants were examined on the experience of acute physical symptoms, and the experiments were done in a single session and in a highly regulated environment, making it difficult to translate these findings to patients with persistent physical symptoms in clinical care.…”

Susceptibility to Nocebo Hyperalgesia, Dispositional Optimism, and Trait Anxiety as Predictors of Nocebo Hyperalgesia Reduction

“…‡P <0.05. This study entails additional exploratory analyses on a larger study, 5 conditioning serving as the control group. The role of dispositional optimism, trait and state anxiety, pain catastrophizing, fear of pain, and body vigilance in the induction and reduction of nocebo hyperalgesia were explored.…”

“…Again, 20 learning phase trials and 6 testing phase trials from part 2 followed. After the end of the experiment, the electrodes were removed from the arm, and participants were asked to fill in exit questionnaires, which were reported elsewhere 5. Afterward, participants were debriefed and reimbursed for their participation.…”

“…Among these, extinction works by no longer reinforcing,7 or in other words no longer strengthening, the association between pain increase and a (sham) treatment, whereas counterconditioning is a method actively targeting the reversal of painful associations with a (sham) treatment. Findings suggest that counterconditioning is a more successful method for reducing nocebo hyperalgesia than extinction 3,5. However, research is still lacking on which individual differences predict susceptibility to nocebo effects or, equally importantly, the recovery therefrom.…”

“…2 Recently, studies have investigated the learning processes for reducing nocebo effects. [3][4][5][6] Among these, extinction works by no longer reinforcing, 7 or in other words no longer strengthening, the association between pain increase and a (sham) treatment, whereas counterconditioning is a method actively targeting the reversal of painful associations with a (sham) treatment. Findings suggest that counterconditioning is a more successful method for reducing nocebo hyperalgesia than extinction.…”