Pain requires the integration of sensory, cognitive, and affective information. The use of placebo is a common methodological ploy in many fields, including pain. Neuroimaging studies of pain and placebo analgesia (PA) have yet to identify a mechanism of action. Because PA must result from higher order processes, it is likely influenced by cognitive and affective dimensions of the pain experience. A network of brain regions involved in these processes includes the anterior and posterior insula (A-Ins, P-Ins), dorsal anterior cingulate cortex (DACC), dorsolateral prefrontal cortex (DLPFC), and the supplementary motor area (SMA). We used connectivity analyses to investigate the underlying mechanisms associated with Placebo analgesia in a group of chronic pain patients. Structural equation models (SEM) of fMRI data evaluated the inter-regional connectivity of these regions across three conditions: (1) initial Baseline (B1), (2) placebo (PA), and (3) Placebo Match (PM). SEM results of B1 data in the left hemisphere confirmed hypothesized regional relationships. However, inter-regional relationships were dynamic and the network models varied across hemispheres and conditions. Deviations from the B1 model in the PA and PM conditions correspond to our manipulation of expectation for pain. The dynamic changes in inter-regional influence across conditions are interpreted in the context of a self-reinforcing feedback loop involved in the induction and maintenance of PA. Although it is likely that placebo analgesia results partly from afferent inhibition of a nociceptive signal, the mechanisms likely involve the interaction of a cognitive-affective network with input from both hemispheres.

Placebo effects can act as powerful pain relievers. While the ethics of therapeutic placebo use is highly controversial, recent evidence suggests that medical providers frequently utilize placebo treatments, and patients may be open to these interventions under certain contexts. This investigation used a patient-centered approach to answer essential questions about placebo treatment acceptability. People with chronic musculoskeletal pain completed a placebo survey where they: 1) rated their knowledge of placebo and its efficacy for alleviating pain; 2) evaluated the acceptability of a placebo analgesic interventions across several unique medical contexts; and 3) responded to six different patient-physician treatment scenarios to assess the role of deception and placebo effectiveness on mood and provider trust. Results showed that participants had limited knowledge of placebo and it’s efficacy for alleviating pain. Placebo acceptability was highly dependent on the context of the intervention, as placebo treatments were considered acceptable when used as complementary/adjunct treatments and when no other established treatments were available. Also, an analgesic placebo response mitigated the negative consequences of deception by improving provider trust and decreasing negative mood. These findings suggest that patients may be rather pragmatic in their appraisals of placebo treatment acceptability and may consider a variety of treatments/contexts as permissible for managing their pain. This is the first study of its kind to quantify perceptions of placebo analgesia knowledge and efficacy among individuals with chronic pain, and to assess the role of different medical contexts in treatment acceptability.

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After a 3-wk gastrocnemius-stretching program, when measuring dorsiflexion with the STJ positioned in supination, the participants who completed a 3-wk gastrocnemius stretching program with the STJ positioned in pronation showed more increased dorsiflexion at the ankle/rear foot than participants who completed the stretching program with the STJ positioned in supination.