Functional brain interactions that serve cognitive–affective processing during pain and placebo analgesia

Abstract

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.

Prefrontal hemodynamic mapping by functional near-infrared spectroscopy in response to thermal stimulations over three body sites

“…[18][19][20][21][22] Furthermore, the role of prefrontal regions in pain, placebo analgesia, and their modulations by analgesic drugs is also demonstrated. 23,24 These studies provided us with the motivation to further explore the role of the prefrontal cortical regions in cognitive evaluation of pain by using functional near-infrared spectroscopy (fNIRS).…”

Placebo response to manual therapy: something out of nothing?

“…Placebo hypoalgesia appears related to descending inhibition of pain from the supraspinal structures and functional MRI is beginning to clarify specific brain regions likely involved in placebo hypoalgesia. Current studies suggest that placeborelated hypoalgesia is associated with responses in regions of the brain related to pain modulation, [45][46][47] emotion, [47][48][49] and cognitive appraisal. 41,48 Both the opioid system 50,51 and the reward system 52,53 are involved in placebo-related hypoalgesia and brain imaging further supports these relationships.…”

“…Current studies suggest that placeborelated hypoalgesia is associated with responses in regions of the brain related to pain modulation, [45][46][47] emotion, [47][48][49] and cognitive appraisal. 41,48 Both the opioid system 50,51 and the reward system 52,53 are involved in placebo-related hypoalgesia and brain imaging further supports these relationships. 54,55 Additionally, the placebo effect is significantly lessened in patients with Alzheimer's disease with pre-frontal cortex involvement 56 and can be abolished with experimental disruption of the prefrontal cortex through transcranial magnetic stimulation.…”

Modeling of Circuits within Networks by fMRI

“…This category includes structural equation modeling (SEM) [56][57][58][59][60][61][62], multivariate autoregressive (MAR) modeling [63,64], dynamic causal modeling (DCM) [65][66][67], generative models including neural mass models [68,69] and large-scale neural models [70][71][72].…”

“…An increasing number of PET, fMRI and transcranial magnetic stimulation (TMS) studies have used SEM to investigate large-scale functional brain networks [90][91][92][93] and show specific networks involved in either working memory [94][95][96][97][98][99][100], attentional processes [64,[101][102][103], face perception [104][105][106], motor movement processing [61,[107][108][109][110][111][112], language [32,113,114] or processing of painful stimuli [62].…”