(139) Mechanisms of Placebo Analgesia: fMRI identifies sustained and transient regional involvement

Abstract

Placebo analgesia (PA) is known to decrease neural activity in pain-related brain regions including the thalamus, somatosensory cortices, insula, and anterior cingulate cortex. However, little is known about the regions that generate the PA response. Using fMRI, our previous work provided indirect evidence that afferent inhibition was in part responsible for PA. Furthermore, we have shown that over time, PA increases while expectation for pain decreases. This inverse relationship suggests: i) the involvement of a self enhancing feedback mechanism in generating the PA response, and ii) that differential neural networks are involved in processing and modulating pain related information. To better understand pain modulation in the brain, the study examined areas of the brain where activity increased during placebo analgesia and how that activity changed over time. Brain regions with consistently higher levels of activity during PA include: frontal, posterior cingulate, bilateral aspects of the temporal lobes, amygdala, and perihippocampal cortices. These brain regions are likely involved in: i) afferent inhibition, via involvement of pain-inhibitory mechanisms that descend from the brain to the spinal cord, and ii) decreased pain-related activity. Activity among these brain regions may reflect the engagement of higher-order pain-related processes. The activity among the brain regions involved with a self-reinforcing PA mechanism should vary with time (i.e., time*condition interaction). Regions with unique early PA activity included the frontal lobe (precentral gyrus), cingulate, insula, and temporal lobe (fusiform gyrus). Of interest, most of these regions are associated with cognitive and emotional processes and there was greater involvement of the left versus right hemisphere, which is commonly associated with neurolinguistic processes. To our knowledge, this is the first time fMRI has been used to identify the temporal development of PA and a neural network likely involved in transforming a placebo suggestion into an endogenous analgesic to relieve pain.