The dynamic mechanisms of placebo induced analgesia: Evidence of sustained and transient regional involvement.

Previously, we demonstrated that placebo analgesia (PA) accompanies reductions in neural activity during painful stimulation. This study investigated areas of the brain where the neural activity was increased during PA. The literature has associated PA with two potential mechanisms of action; one sustained (e.g., engaged for the duration of PA), the other, transitory (e.g., a feedback mechanism). We propose that PA results from the engagement of two complementary pain-modulation mechanisms that are identified with fMRI data as a main effect for condition or a time *condition interaction. The mechanism with sustained activity should activate the emotional regulation circuitry needed for memory formation of the event. The mechanism with transient activity should process cognitive and evaluative information of the stimuli in the context of the placebo suggestion to confirm the expectations set by it. To identify regions involved with these mechanisms, we re-analyzed fMRI data from two conditions: baseline (B) and PA. Results support the presence of both mechanisms, identified as two neural-networks with different temporal characteristics. Regions with sustained activity primarily involved the temporal and parahippocampal cortices. Conversely, brain regions with transient activity included linguistic centers in the left hemisphere and frontal regions of the right hemisphere generally associated with executive functioning. Together, these mechanisms likely engage analgesic processes and then simply monitor the system for unexpected stimuli, effectively liberating resources for other processes. Identifying brain regions associated with pain-modulation with different temporal profiles is consistent with the multidimensionality of PA and highlights the need for continued investigation of this construct.