Probably something like this:
Placebo effect and the brain
Functional imaging upon placebo
analgesia shows that it links to the activation, and increased functional correlation between this activation, in the
anterior cingulate,
prefrontal,
orbitofrontal and
insular cortices,
nucleus accumbens,
amygdala, the brainstem
periaqueductal gray matter,
[64][65][66] and the
spinal cord.
[67][68][69][70]
These changes can act upon the brains early stages of information processing: research using
evoked brain potentials upon painful laser pulses, for example, finds placebo effects upon the N2P2, a biphasic negativepositive complex response, the N2 peak of which is at about 230 ms, and the P2 one at about 380 ms.
[30] They occur not only during placebo analgesia but after receiving the analgesic placebo (the areas are different here, and involve the
medial prefrontal cortex,
posterior parietal cortex and
inferior parietal lobule).
[71]
Different areas in the higher brain have different functions. The prefrontal involvement could be related to recalling the placebo and maintaining its cognitive presence in a "self-reinforcing feedback loop" (during pain an individual recalls having taken the placebo and reduced pain reinforces its status as an analgesic).
[72] The rostral anterior cingulate cortex (rACC) and its subcortical connectivity could be related to the expectation of potential pain stimuli
[73][74]
The higher brain works by regulating subcortical processes. High placebo responses link with enhanced
dopamine and
mu-opioid activity in the circuitry for reward responses and motivated behavior of the nucleus accumbens, and conversely, anti-analgesic nocebos responses were associated with deactivation in this part of the brain of dopamine and opioid release.
[65] (It has been known that placebo analgesia depends upon the release in the brain of
endogenous opioids since 1978.
[75]) Such analgesic placebos activation changes processing lower down in the brain by enhancing the descending inhibition through the periaqueductal gray
[65] on spinal
nociceptive reflexes, while the expectations of anti-analgesic nocebos acts in the opposite way to block this.
[67]
The brain is also involved in less studied ways upon nonanalgesic placebo effects:
- Parkinson's disease: placebo relief is associated with the release of dopamine in the brain.[76]
- Depression: Placebos reducing depression affect many of the same areas that are activated by antidepressants with the addition of the prefrontal cortex[77][78]
- Caffeine: placebo caffeinated coffee causes an increase in bilateral dopamine release in the thalamus.[79]
- Glucose: the expectation of an intravenous injection of glucose increases the release of dopamine in the basal ganglia of men (but not women).[80]
- Methylphenidate: the expectation of intravenous injection of this drug in inexperienced drug users increased the release of dopamine in the ventral cingulate gyrus and nucleus accumbens, with this effect being largest in those with no prior experience of the drug.[81]
Present functional imaging upon placebo analgesia has been summarized as showing that the placebo response is "mediated by
"top-down" processes dependent on frontal cortical areas that generate and maintain cognitive expectancies.
Dopaminergic reward pathways may underlie these expectancies".
[82] "Diseases lacking major 'top-down' or cortically based regulation may be less prone to placebo-related improvement".
[83]
Placebo - Wikipedia, the free encyclopedia