In a randomized, double-blind, placebo-controlled trial of 65 cancer survivors with chronic musculoskeletal pain, participants who reported more pessimistic, so-called nocebo, expectations about their assigned patch showed 2.5 points less improvement on a 0-10 pain scale by day 14 than those with lower nocebo expectations, and were 42.7 percentage points less likely to reach a meaningful reduction in pain (p<0.001 for both), according to results published in Biomedicine & Pharmacotherapy. The pattern held whether a participant had been given the real 1 percent camphor patch or a matching inert patch, and regardless of how optimistic, or placebo-oriented, their expectations were.
The trial was run at Memorial Sloan Kettering Cancer Center as part of a phase II study registered as NCT04916249, testing a camphor-based topical analgesic for chronic pain in cancer survivors. Participants applied either the active patch or a look-alike placebo patch daily for 14 days. Before treatment began, the research team, led by Mingxiao Yang with senior author Jun J. Mao, had each participant complete validated questionnaires that separately captured how much benefit they expected (placebo expectation) and how much harm or lack of benefit they expected (nocebo expectation). Pain was then tracked with the worst-pain item of the Brief Pain Inventory.
The authors reported that nocebo expectations, not placebo expectations, predicted both worse pain outcomes and more reported side effects; higher hopes for relief did not reliably improve results in either the drug group or the placebo group. That asymmetry, they wrote, raises the possibility that negative expectations may amplify pain signals through central pain sensitization, though they describe this mechanism as a hypothesis, not a demonstrated pathway.