Feasibility and Acceptability of OLP-EXP in Chronic Pain

Pain lasting for more than 3 months becomes chronic, and is prevalent across the global population. Among chronic pain conditions, temporomandibular disorders (TMD), a common orofacial pain condition affecting 9 to 30% of the general population, have attracted the attention of clinical providers and researchers. The high incidence and disastrous consequences of TMD underscore the need for effective and safe treatments.

Clinical and mechanistic research has shown substantial placebo responses in pain trials, highlighting the great potential to harness placebo mechanisms in clinical care. For example, a meta-analysis estimated that placebo responses could account for up to 66% of observed improvement in migraine-related outcomes.8 In one efficacy and safety trial of an intravenously eptinezumab, as much as 74% of the apparent benefit was attributed to placebo responses.

In ethically translating placebo mechanisms, open-label placebo (OLP) offers an adjuvant to current pharmacological and psychological treatments for chronic pain. OLP refers to the transparent, honest administration of placebos. Studies have found that people can still experience improvements in symptoms even after receiving OLP.

Previous RCT has demonstrated efficacy of EXPECT in a pilot clinical trial showing a reduction in the length of hospital stay after cardiac surgery. Moreover, participants who received EXPECT showed greater improvements in disability, and reduced pro-inflammatory cytokine concentrations compared to those in the treatment as usual group.

We aim to develop an expectation-optimized OLP intervention (OLP-EXP) that could potentially maximize OLP effects and yield larger improvement in managing chronic pain, and an EXP only intervention that delivers expectations induced analgesia without the negative connotations of "placebo".

We hypothesize that the adapted OLP-EXP and EXP only will be feasible and well-accepted in chronic pain population.

This is a single-site, three-arm, parallel-group, randomized pilot/feasibility clinical trial. Fifty-seven adults with chronic TMD will be randomized 1:1:1 to OLP-EXP, EXP only, or OLP only. All participants will continue treatment as usual. The intervention period is 6 weeks, followed by remote assessments at 3, 6, and 12 months.

The intervention arms are:

• OLP-EXP: Expectation optimization addressing benefit, personal-control, and coping expectations, plus transparent daily OLP pills for 6 weeks and weekly boosters.
• EXP only: Expectation optimization addressing personal-control and coping expectations associated with chronic pain in general, plus weekly boosters.
• OLP only: Standard transparent OLP rationale and daily OLP pills for 6 weeks, with neutral matched study contacts that do not deliver expectation-optimization content.

Inclusion criteria

• English speaking (written and spoken)
• Age between 18 and 65 years
• Confirmed TMD for more than 3 months
• Grade II or above on the Graded Chronic Pain Scale

Exclusion criteria

• Personal (or family first degree) history of mania, schizophrenia, or other psychoses
• Severe psychiatric conditions require medication (e.g. schizophrenia, bipolar disorders, autism) or hospitalization within the last 3 years.
• Lifetime alcohol/drug dependence and alcohol/drug abuse in past one year
• Pregnancy/Breastfeeding
• Currently participating in another clinical trial