Introduction: Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients' expectations may affect the capacity to respond to placebos in chronic disorders. Objective: The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. Methods: We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. Results: In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. Conclusions: These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clinical trial designs.

These findings demonstrate that depression and anxiety worsened while clinical pain improved during the State-at-Home period of the pandemic suggesting a shift in symptoms perception.

Supraspinal descending pathways from the periaqueductal gray and rostral ventromedial medulla dynamically modulate nociceptive transmission in the spinal dorsal horn. We examined the expression of the brain-derived neurotrophic factor receptor trkB in response to inflammation. No difference was observed in the number of neurons expressing trkB in the periaqueductal gray or rostral ventromedial medulla 3 h after inflammation; however, by 24 h, there was a significant increase in trkB expression in the periaqueductal gray (P < 0.05) and rostral ventromedial medulla (P < 0.05), compared with naïve levels, which persisted to 7 days and returned to naïve levels by 21 days. These results demonstrate a temporal increase in the number of cells expressing trkB in response to persistent inflammation, suggesting a role for trkB signaling in activity-dependent plasticity in the pain modulatory circuitry.

Background Temporomandibular disorders (TMD) symptoms develop into chronic pain for some patients, but the reasons for this are unclear. Psychosocial factors and chronic overlapping pain conditions are believed to contribute to the development of pain‐related disability. We examined the role of jaw function, negative and positive psychological factors and chronic overlapping pain conditions (COPCs) on pain‐related disability whilst controlling for demographic variables. Methods We collected demographics, medical and psychosocial history and the Graded Chronic Pain Scale, a measure of pain intensity and pain interference from 400 participants with chronic TMD. Structural equation modelling was used to assess a model of COPCs and the latent variables of psychological unease (pain catastrophizing, somatic symptoms and negative affect), positive valence factors (optimism and positive affect), jaw function (chewing, opening and expression limitation) and pain‐related disability (pain intensity and pain interference) whilst controlling for demographic variables. Results We achieved good fit of a parsimonious model (root‐mean‐square error of approximation = 0.063 [90% CI] [0.051–0.075]), comparative fit index = 0.942, standard root‐mean‐square residual = 0.067. Jaw function was the strongest latent variable predictor, followed by psychological unease and COPCs suggesting resources focused on improving joint function, psychosocial support and management of COPCs will improve pain‐related disability in TMDs. Conclusions These findings not only increase the body of knowledge related to TMD clinical phenotypes but also, have a translational impact in further supporting the potential value of targeting physical therapy such as jaw exercise along with psychological interventions as multidisciplinary nonpharmacological therapeutic solutions.

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