Associative and Observational Learning of Nocebo Effects on Itch

In this study on healthy adult female volunteers we are investigating the efficacy of conditioning and observational learning for inducing nocebo effects on cowhage-evoked itch. Using a mixed model design, nocebo effects will be induced and measured within two active conditions (conditioning and observational learning), and compared to a third, control group of sham conditioning. Cowhage is a tropical plant that creates a brief itching sensation when rubbed into the skin, and is believed to act on the peripheral nociceptive pathways involved in pruritic symptoms in chronic dermatological conditions (e.g. Atopic Dermatitus).

1. Primary: A nocebo effect on cowhage-evoked itch will be induced through a conditioning with verbal suggestion paradigm, as measured by a larger difference in perceived itch during nocebo-associated and control test phase trials for the active conditioning group compared to the sham conditioning group.
2. Secondary: A nocebo effect on cowhage-evoked itch will be induced through observational learning of a conditioning paradigm, as measured by a larger difference in perceived itch during nocebo-associated and control test phase trials for the observational learning group compared to the sham conditioning group.
3. Exploratory 1: A nocebo effect on itch will generalize to increased frequency and duration of scratching responses when induced with a classical conditioning and verbal suggestion paradigm, compared to the frequency and duration of scratching responses in the sham conditioning group
4. Exploratory 2: A nocebo effect on itch will generalize to increased frequency and duration of scratching responses when induced with an observational learning paradigm, compared to the frequency and duration of scratching responses in the sham conditioning group
5. Exploratory 3: The following psychological constructs will be measured with self-report surveys to test exploratory hypotheses that these variables may act as moderators for the magnitude of nocebo effects on itch induced with conditioning or observational learning:
• Empathy
• Anxiety
• Social desirability
• Mindfulness
• Stress
• Mood
• Sleep quality

Participants complete an online survey from home, lasting approximately 20 minutes, prior to an approximately 90 minute appointment in the lab where the experimental procedure is conducted and the primary outcome is assessed.

Conditioning: Participants will undergo a conditioning paradigm acquisition phase consisting of four cowhage administrations. A verbal suggestion is made, informing participants that one of two creams applied prior to the cowhage will intensify the itch that they feel from the cowhage, For each trial, the researcher will act as though they are applying a small unit of one of the creams to one of the 2x2cm squares. The control trials are paired with a lower dose of cowhage, and the nocebo associated trials are paired with a larger dose of cowhage so that more itch is experienced during the nocebo-associated learning trials.

The order of the learning phase trials is fixed, consisting of 1) a control trial, 2) a nocebo-associated trial, 3) a control trial, and 4) a nocebo-associated trial.

Observational learning: Participants in the observational learning group will watch a video which depicts the conditioning acquisition phase procedure described above with a model participant. The model participant gives an average rating of 30 (on a 0-100 scale) for the control trials and an average rating of 60 for the nocebo-associated trials.

Sham conditioning: Participants in the sham conditioning group complete the same conditioning procedure described above, however each trial uses only the low dose of cowhage, so that no difference in itch between the two creams is perceived.