Indian neurologist V.S.
Ramachandran relates an experiment in which he used a cotton swab to touch
various locations on the body of a patient whose left arm had been amputated.
When Ramachandran touched the left side of the patient’s face, he cried
out in surprise, because it felt as if someone were touching the thumb on his
amputated left hand. And when Ramachandran moved the cotton swab to the patient’s
upper lip, the patient then reported that the neurologist was touching his phantom
This observation, in which heat, cold, or a tactile stimulus
applied to the face can sometimes be felt in a phantom
limb, has been repeated many times. Similarly, a touch applied to the genitals
can sometimes be felt in a phantom amputated foot.
The explanation for
these strange observations lies in the fact that the somatosensory
cortex contains a complete though distorted map of the body’s surface,
in which the face is represented alongside the hand. When someone’s hand
has been amputated, in the absence of any sensory input from that hand, the
inputs from the face gradually invade the cortical area dedicated to the hand.
That is why when a stimulus is applied to the face of someone whose hand has been
amputated , he or she will often feel it in two locations: the face and the phantom
This reorganization of the cerebral cortex after
an amputation constitutes yet another proof that the cortex retains a very high
degree of plasticity
even in adults. But this phenomenon may have its downside: some researchers believe
that this “colonization”, by other body parts, of the part of the
cortex associated with an amputated member may also be the origin of phantom pain.
Indeed, some studies have shown that the greater this plasticity, the more intense
the phantom pain.
After a brain injury, some people
experience a veritable disconnection from the emotional component of pain. This
condition is known as pain asymbolia. The people who have it
can perceive and locate pain, but do not feel the negative emotions usually associated
In almost all cases, the injuries to these people’s brains
involve the posterior part of the insula
and the parietal operculum—in other words, the base of the postcentral gyrus,
which is the locus of somatosensory discrimination. The neurons in these structures
perform complex functions. For example, they respond to nociceptive somatosensory
stimuli as well as to visible threats to the body’s integrity. Individuals
in whom these brain structures have been totally or partially destroyed cannot
integrate these kinds of information and so cannot translate them into pain-avoidance
One can see how this loss of the sense of threat and danger
would lead to the surprising emotional disconnection that characterizes this syndrome.
Emotion and the motivation to react are very closely related, in evolutionary
terms, because emotions can can promote adaptive reactions. If someone with pain
asymbolia gets bitten by a dog, and then laughs at the pain instead of trying
to get away, it’s reasonable to say that this behaviour is not highly adaptive.
existence of so many different ascending pathways for pain suggests that they
do not all depend on a single system terminating in a “pain centre”
somewhere in the brain. On the contrary, the perception of pain is controlled
by a number of different brain structures, which confirms the multi-faceted nature
of this phenomenon.
Once a pain message
has passed through the reticular
formation in the brainstem and on to certain nuclei in the thalamus, it reaches
the cerebral cortex. The primary somatosensory
cortex (S1) receives the axons of the neurons of the ventral posterolateral
nucleus (VPL) of the thalamus, while the secondary somatosensory cortex
(S2) receives pain messages both from S1 and from the thalamic nuclei.
Neuroscientists generally assign S2 a role in recognizing pain and remembering
past pain, while associating S1 with discriminating the various properties of
The preservation of somatotopic
organization all the way up to the S1 cortex is what lets the brain determine
the location of pain in the body, while the activity level of the neurons in S1
corresponds to the intensity of the pain stimulus. For example, if you place your
hand under a running hot-water tap, the hotter the water gets, the more nerve
impulses the neurons in your S1 cortex will generate. Brain-imaging studies have
shown that the higher the neural activity level in S1, the more intense the pain,
as evaluated subjectively by the individual concerned.
other studies, hypnosis was used to suggest to the subjects that a pain stimulus
was less intense than it actually was. Brain images then showed that under these
conditions, the activity level in the S1 cortex decreased. Remarkably, however,
when a stimulus of the same intensity was applied to all of the subjects, but
some were given the hypnotic suggestion that it would be very painful and others
that it would not, the activity level in the S1 cortex remained constant among
all the subjects. However, in the anterior cingulate cortex,
whose activity level is associated with the affective component of pain, this
level varied with the nature of the suggestion, thus confirming that these two
areas play distinct roles in the perception of pain.
from Price, D.D. (2000) Science Vol. 288, pp. 1769-1772
we can thus see, brain-imaging tools enable neuroscientists to draw associations
between particular structures in the brain and the various dimensions of the complex
phenomenon commonly referred to as pain. Together, these interconnected areas
of the brain form what is known as the pain
matrix. Its various components may be associated specifically, but not exclusively,
with the anticipation of pain, the discrimination of pain, or, as is the case
for the anterior cingulate cortex, with the unpleasant affective manifestations
for this association between the negative affect of pain and the activity of the
anterior cingulate cortex is that this structure incorporates sensory inputs,
including pain stimuli, into cognitive processing, so as to allow the production
of appropriate motor responses, such as avoidance behaviours. Because emotions
give rise to motivations which in turn give rise to actions, one can readily understand
the importance of the anterior cingulate cortex in affective reactions to pain
that require an immediate behavioural response.
the anterior portion of the cingulate cortex is the one most often discussed in
the pain literature, research by German neuroscientist Burkhart Bromm has shown
that the posterior cingulate cortex responds
to nociceptive messages first (about 220 milliseconds after the nociceptive stimulus
is applied). This activity then moves on to the medial and anterior portions of
the cingulate cortex, before subsiding in the frontal cortex about 300 milliseconds
after the stimulus began.
Scientists also believe
that the posterior cingulate cortex may merge the negative affect of pain, along
with its location, nature, and intensity, into a single unified perception, through
its connections to the parietal cortex,which plays a recognized
role in integrating various sensory modalities.
posterior portion of the parietal cortex is also involved in attention to painful
stimuli. So is the dorsolateral region of the right prefrontal cortex, another
part of this attentional network in the cortex. Researchers are well aware that
from a painful stimulus can substantially diminish the subjective sensation of
pain, and that this subjective sense of comfort is accompanied by an objective
decrease in activity in the parts of the brain that are associated with pain.
The prefrontal cortex is involved
not only in the “higher” functions, which often involve attention,
but also in learning nociceptive sensations and hence in developing negative affect
associated with them. Hence the prefrontal cortex is extremely well placed to
play a role both in anticipating and controlling pain.
example, in experiments where subjects’ brain activity was monitored while
they were anticipating and actually receiving painful electric shocks, two conditions
were used. In one, a cream was applied to the place on the subjects’ bodies
where they were going to receive the shock, and they were told that this cream
was an analgesic, whereas actually, it was only a placebo.
In the other condition, no placebo was used. When the shock was administered to
the subjects who had received the placebo, they reported less pain and showed
less neural activity in some brain areas associated with pain, such as the thalamus,
the primary and secondary somatosensory cortexes, the anterior cingulate cortex,
and the insular
cortex (also known simply as the insula). In contrast, while these same subjects
were anticipating the shock (and, presumably, the pain relief associated with
the placebo), they showed greater electrochemical
activity in their prefrontal cortex and in an area of the midbrain that includes
the periaqueductal grey matter.
Because the prefrontal
cortex is also associated with certain forms of working
memory—in other words, with temporarily storing ideas, information,
and thoughts so that they can be processed cognitively—one can readily see
how this function might enable it to play a role in the anticipation of pain relief
that is the source of the placebo effect.
As for the
periaqueductal grey matter, its activation in parallel with the
prefrontal cortex during the anticipation of relief from pain tends to support
hypothesis that prefrontal mechanisms trigger the release of endogenous
opioids in the periaqueductal grey matter when the placebo effect is experienced.
In addition, this nucleus in the midbrain receives information from numerous other
brain structures associated with the integration of emotional processes.
periaqueductal grey matter and the area around it also receive inputs from the
nociceptive fibres; these inputs too can trigger the descending
control mechanisms that this area applies to the neurons
of the dorsal horn of the spinal cord.
now know that this endogenous analgesia can be triggered by the stimulation of
several other subcortical structures, running from the medulla oblongata to the
diencephalon. These structures include the raphe nucleus (which, along with the
periaqueductal grey matter, has one of the most powerful analgesic effects), as
well as the lateral reticular nucleus, the nucleus of the solitary tract, the
locus coeruleus, the parabrachial area, and the lateral hypothalamus.
subcortical structures also contribute to various pain-related phenomena. For
instance, the transmission of nociceptive information from the reticular formation
and the non-specific thalamus to the hypothalamus—perhaps
the most important autonomic regulatory structure in the brain—increases
the secretion of stress
hormones and the activation of the sympathetic
nervous system. The same projections, by activating the striatum,
also encourage the largely automatic motor alarm responses triggered by pain stimuli.
The significant interconnections between the anterior
cingulate cortex and the amygdala,
a key site for affective visceral regulation, account for the sweating, accelerated
heart rate, elevated blood pressure, and nausea caused by intense pain.
particular anatomical location, and its close connections with the
system, make it an ideal candidate to serve as an interface between sensory
information from a person’s body and that person’s particular cognitive
state at any given moment. And a subjective sensation such as pain is constituted
precisely through the combination of this sensory and cognitive information. The
insula, and more especially the right anterior insula, is one of the brain structures
most commonly activated not only directly by a pain stimulus, but also when people
look at pictures of painful situations and imagine themselves experiencing them.
Indeed, research on the neuronal
substrates of empathy shows that there is a partial overlap between the areas
of the brain that are active when an individual is experiencing pain and those
that are active when he or she sees someone else in pain, and that the overlapping
areas include the anterior cingulate cortex and the insula. In contrast, however,
looking at an image that evokes fear
(another negative emotion associated with pain) causes increased activity in the
anterior cingulate cortex and in structures such as the amygdala, but not in the
insula. Thus, though both fear and pain cause unpleasant emotional states associated
with reactions of withdrawal and protection, their neurological substrates overlap