PSYCHO-AFFECTIVE DISORDERS AND PAIN
PAIN AND PSYCHO-AFFECTIVE DISORDERS
Giovanni Broggi, M.D.
Department of Neurosurgery,
Istituto Neurologico C. Besta,
Milan, Italy
Reprint requests:
Giovanni Broggi, M.D.,
Department of Neurosurgery,
Istituto Neurologico C. Besta,
Via Celloria 11, 20133,
Milan, Italy.
Email: gbroggi@istituto-besta.it
Received, August 2, 2007.
Accepted, April 7, 2008.
Neurosurgery 62[SHC Suppl 3]:SHC-901–SHC-920, 2008
NEUROSURGERY
THE SUBJECT OF human pain can be subdivided into two broad categories: physical pain and
psychological pain. Since the dawn of human consciousness, each of these two forms of pain—
one clearly physical, the other having more to deal with the mind—have played a central role in
human existence. Psychological pain and suffering add dimensions that go far beyond the bound-
aries of its physical counterpart.
In the past 50 years, one of the more remarkable accomplishments of medical science has
been to increasingly enable the clinician to impact, as never before, each of these critical realms
of human existence.
Our intention is, therefore, to initially describe a few of the many exciting neuroscientific and
neurosurgical advances that have been made in the treatment of various types of pain and to
speculate on some of the emergent questions that we believe need to be addressed. After this is
accomplished, we will then use this information as a kind of two-pronged philosophical entrance
into questions of the mind, brain, and soul that we feel are necessary to bring back into the sphere
of the modern physician’s practice.
The goal of this article is two-fold: 1) to share some of our exciting research and 2) to renew
the interest in timeless questions, such as that of the mind-brain and the brain-mind, in the con-
versation of the modern neurosurgeon.
The International Association for the Study of Pain divides pain into two broad functions and
anatomical categories. In this framework, “nociceptive” pain is defined as the kind of physical
pain that results when the tissue is damaged. Given this perspective, such pain is usually consid-
ered a consequence of one’s defense against one’s environment. The other pain is the “neuro-
pathic” one resulting from a lesion or a dysfunction of the human nervous system.
As such, we will take the risk of crossing beyond the boundaries of neurosurgery and venture
into boundaries that, at another time, might seem more natural to the discipline of psychiatry for
two reasons. The first is that psychiatry seems to be so focused on the brain—its biochemistry
and pharmacology—that questions of mind and soul have become rare and almost negligible. The
second is to follow the course of the results of our own clinical investigations that have taken us
into that very human world where questions of physical pain, psychological pain, and the expe-
rience of suffering abound.
Today, however, the strategy of neuromodulation offers the advantage of being precisely tailored
in neuroanatomical terms and, even more importantly, of being altogether reversible. At both our
own Istituto Neurologico C. Besta and many other neurosurgical centers worldwide, many proce-
dures have been reported in which implant neuromodulation devices successfully treat pain.
For example, long-term stimulation of the spinal cord has been fairly effective in the treatment
of neuropathic pain, multiple sclerosis, and various other forms of pain. Good results have been
obtained in treating peripheral vascular diseases and sympathetic reflex dystrophy syndrome.
Good results have also been achieved in trigeminal nerve stimulation and peripheral nerve stim-
ulation. In the case of thalamic stimulation, there has also been an improvement of symptoms,
but a long-term degree of tolerance was noticed. Hypothalamic stimulation has also been seen to
be effective in controlling trigeminal autonomic cephalalgic pain, as well as the facial pain that
is known to occur in multiple sclerosis. Motor cortex stimulation was found to occasionally have
good results in treating neuropathic pain, whereas occipital nerve stimulation was found to achieve
good results in controlling chronic cluster headache and other chronic headaches, although with
only short-term follow-up so far. Recent reports of functional magnetic resonance imaging have
prompted us to propose exciting new neurosurgical targets that may be effective in treating psy-
choaffective disorders. Our results appear to be more than promising so far. It appears that neu-
ropathic pain and psychoaffective disorders seem to be sharing an anatomophysiological com-
mon background at the Brodmann Area 25 of the anterior cingulated gyrus. On the basis of these
exciting findings, we believe that it is reasonable to suggest that neuropathic pain and psychoaf-
fective disorders may ultimately be managed with complementary or, at least, similar, therapeu-
tic strategies, each of which lie within the domain of the neurosurgeon.
KEY WORDS: Affective disorders, Neuropathic pain, Pain, Psyche, Psychosurgery
DOI: 10.1227/01.NEU.0000317337.51936.43
VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT | SHC901
BROGGI
T
he subject of human pain can be divided into two broad
categories: physical pain and psychological pain. Since
the dawn of human consciousness, each of these two
forms of pain—one clearly physical, the other having more to
do with the mind—has played a central role in human exis-
tence. Historically and etymologically, the word “pain” has
close ties to negative or unpleasant experiences and an unmis-
takable linkage to the concept of punishment. Not surprisingly,
however, dramatic differences emerge when we consider pain
of a more psychological or spiritual nature. Psychological pain,
in addition to suffering—pain’s closely related experiential
counterpart—although unmistakably bound to the idea of pun-
ishment and possessing a long history in human existence, has
added dimensions that go far beyond the boundaries of its
physical counterpart. Primary among these are its close linkage
with death, its historical linkage with spirituality and religion,
and not surprisingly, its connection to the subject of the human
soul. In the past 50 years, one of the more remarkable achieve-
ments of medical science has been the increasing ability of the
clinician to affect each of these critical realms of human exis-
tence as never before. Because of these dramatic therapeutic
inroads made possible by the advances of science, the modern
physician may now be closer to routinely treating what were
previously considered to be nonclinical situations related to
philosophers and intellectual discussions of the mind and the
brain. It is precisely because of these advances that we have
written this paper, with the hope of clarifying a number of
heretofore philosophical issues that we believe must now be
part of the clinician’s knowledge—not only to anticipate many
labyrinthine ethical situations, but also because we believe this
kind of metaphysical-philosophical inquiry will produce a bet-
ter physician.
Our intention is, therefore, first to describe some of the many
exciting neuroscientific and neurosurgical advances that have
been made in the treatment of various types of pain (many of
which have come out of our clinical investigations at the C. Besta
Neurological Institute in Milan, Italy) and to elaborate on some
of the emergent questions that we believe need to be addressed.
When this is accomplished, we will then use this information as
a kind of two-pronged philosophical entrance into the ques-
tions of mind, brain, and soul that we believe need to be brought
back into the modern physician’s sphere of practice. Doubtless,
because of medical science’s increasing tendency to apply engi-
neering principles to human existence, the physical body and life
itself have a growing tendency to be seen, almost exclusively,
from an extremely “robotic” or mechanistic perspective. With
advances in the neurosciences that provide convincing evidence
leading us to believe that the brain is a computer and the body
is a machine, we in medicine—and not the philosophers—may
be the ones responsible for shifting the balance created by cen-
turies of thought about humans and of human existence toward
this disturbing “brave new worldview” of soulless, mechanistic
extremism. Our intention is, therefore, twofold: 1) to share some
of our exciting research and 2) to renew interest in timeless ques-
tions, such as that of the mind-brain and the brain-mind, to the
forefront of conversation of the modern neurosurgeon. Our
SHC902 | VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT
urgency is both practical and philosophical and follows the logic
of Socrates, for whom the unexamined life was not worth living.
Following this logic that anticipates the growing importance of
human consciousness, our intention might be stated as follows:
the unexamined clinician’s life is not worth living.
Today’s nervous system clinician generally follows the phys-
ical-materialist guidelines that have been laid down by the
International Association for the Study of Pain (IASP), which
categorizes pain in two broad functional and anatomic cate-
gories. In this framework, nociceptive pain is defined as the
kind of physical pain that results when tissue is damaged; in
this scheme of thinking, such pain is usually perceived of as a
consequence of one’s defense against one’s environment.
Neuropathic pain is the pain that results following an injury to
or a dysfunction of the human nervous system. Often missing
from our clinical and therapeutic maps, however, are the
uniquely spiritual questions of human suffering and psycho-
logical pain. Although this form of pain and suffering often
blurs the distinctions between the normal and pathological,
and probably constitutes the vast majority of all the pain and
suffering that exists at any moment in time, we may be nearing
that moment when our profession, and specifically the neuro-
surgeon, starts to acknowledge this elephant in the room, even
if it complicates the simplicity of our materialistic scientific
paradigms. We are, therefore, consciously running the risk of
crossing beyond the boundaries of neurosurgery and venturing
onto terrain that, at another time, might have seemed more
natural to psychiatry. We are doing this for two reasons. The
first is that psychiatry seems to be so focused on the brain, its
biochemistry and pharmacology, that questions of mind and
soul have become rare, almost nonexistent. The second is to fol-
low the course that follow from the results of our own clinical
investigations, which have taken us into that very human
world where questions of pain, psychological pain, and the
experience of suffering are highly germane.
Though we enter this uniquely human metaphysical world
with a caution and recognition of the importance of staying
close to our results and our data. To evaluate the efficacy of
therapeutic interventions directed to the improvement of pain
syndromes and psycho-affective disorders, it is necessary for
the caregiver to rely heavily on the patient’s subjective report-
ing, which always creates problems when it comes to scientific
conclusions that rely heavily on so-called objectivity. Because
there is, as yet, no known “cure” for pain (or for psycho-affec-
tive disorders, for that matter), our professions have had to
rely on many strategies, most of which have been highly
experimental in nature. In neurosurgery, for example, our
efforts to improve pain symptoms have required that we resort
to strategies that interrupt abnormal neuronal activity in sen-
sory pathways in the hope of interfering with information
being transmitted to higher brain structures. Today, however,
the strategy of neuromodulation offers the advantages of being
precisely tailored in neuroanatomic terms and, even more
importantly, of being altogether reversible. In our own Istituto
Neurologico C. Besta and in numerous other neurosurgical cen-
ters worldwide, many procedures have been reported in which
www.neurosurgery-online.com

implant neuromodulation devices have demonstrated success.
Thus, for example, long-term stimulation of the spinal cord has
been able to achieve a fair degree of efficacy in the treatment of
neuropathic pain, multiple sclerosis, and various other forms of
pain. Good results have been obtained in treating peripheral
vascular diseases and sympathetic reflex dystrophy syndrome.
Good results have also been achieved in trigeminal nerve stim-
ulation and peripheral nerve stimulation. In the case of thala-
mic stimulation, there has also been an improvement of symp-
toms, but a long-term degree of tolerance was noticed.
Hypothalamic stimulation has also been seen to be effective in
controlling trigeminal autonomic cephalalgic pain as well as for
the facial pain that is known to occur in multiple sclerosis. It
was not, however, effective when used to alleviate atypical
facial pain and essential trigeminal neuralgia. Motor cortex
stimulation has been found to achieve good results in treating
neuropathic pain, whereas occipital nerve stimulation was
found to achieve good results in controlling chronic cluster
headache and other chronic headaches, although with only
short-term follow-up thus far. Recent reports of imaging with
functional magnetic resonance imaging have prompted the
proposal of some exciting new neurosurgical targets that may
be effective in the treatment of psycho-affective disorders, and
our results thus far seem to be more than promising. Neuro-
pathic pain and psycho-affective disorders seem to share an
anatomophysiological final common pathway: Area 25 of
Broadmann, the anterior cingulated gyrus. On the basis of these
exciting results and findings, we believe that it is reasonable to
suggest that both of these disorders—psychological pain and
psycho-affective disorders—may ultimately be managed with
complementary, or at least similar, therapeutic strategies that lie
within the domain of the neurosurgeon.
A Brief History of Pain from the
Perspective of Neurosurgery
There are times when etymology, the study of the roots of our
language, can teach the scientist or the physician lessons that
sometimes become lost or obscured as we execute our everyday
activities. This is particularly true when it comes to the words
that we use to describe our pain, our suffering, and life’s more
difficult experiences. When we seek out the etymological roots
of “pain,” we find that it is derived from the Greek “poinè”
and the Latin “poena,” both of which take meaning from pun-
ishment. From this etymological perspective, at least, the con-
nection between pain and punishment becomes immediately
obvious. But what exactly does this tell us as scientists or clini-
cians? When we turn to the Bible, for example, we soon discover
that the human experience of pain is often a direct consequence,
a side effect, if you will, of a more fundamental cause, that is,
God’s displeasure with the creatures of His creation.
In Genesis, we learn that this human experience of pain traces
all the way back to Adam and Eve and, at least in biblical terms,
to the origins of human existence. Following the heavenly out-
burst that resulted in the first human beings, Adam and Eve, it
is said, “you [woman] will deliver in pain.” Given this particu-
lar biblical foundation, at least, it naturally follows that all
NEUROSURGERY
PAIN AND PSYCHO-AFFECTIVE DISORDERS
humanity—every color and race directly descendent from
Eve—must literally begin life with the experience of pain.
In contrast to the etymological connection the Greeks made
between pain and punishment, it is also interesting to note that the
Greeks also had a word for a dimension of pain that we, as clini-
cians, might find much more meaningful. Their word “algos”—the
obvious etymological link to such medical terms as “neuralgia”
and “analgesia” – addresses a different dimension or class of pain,
one that comes closer to what we in neurosurgery would call neu-
roceptive pain. Having no obvious link to punishment, the word
“algos” speaks of the pain that a warrior feels when wounded in
battle. This is the kind of pain that is experienced when a leg is bro-
ken or a child’s skin is stung by a bee. In contradistinction to the
more morally slanted and punitive dimensions of “poinè,” the
word “algos” describes a physiological process that need not be
restricted to the human experience and, in fact, can be expected to
be present throughout the animal kingdom.
The etymology of “suffering” bears a close similarity to both
the biblical as well as the Greek etymological origins of our
word “pain.” Whereas “pain” traces back to punishment, the
etymological origins of the word “suffering” trace back to the
Greek “pherein” and the closely related Latin “ferre,” both of
which simply mean to carry or to bear, a meaning that comes
close to our word “endurance.”
The etymological origins indicate that, at least to the Greeks
and the Romans, there is a clear distinction or dichotomy to be
made between matter and spirit—at least when it comes to the
important human experiences of pain and suffering. Whereas
algos is material or physical, poinè and pherein have an unmis-
takable spiritual quality.
A similar kind of dichotomy can be readily found in the way
that the Greeks and Romans distinguished between the physi-
cal heart, which they called cardiac, and the spiritual heart,
which we celebrate on St. Valentine’s Day. The latter usage of
the word “heart,” which is so central to our language and expe-
rience, is intimately tied up with our emotions, our psycholog-
ical distress and joy, and our affect, whereas the former is
clearly related to the muscle in our chest that pumps our blood
moment by moment.
Though this matter-spirit dichotomy pervades virtually
every aspect of our Western culture, its presence in today’s
world of science and technology is conspicuously deficient.
With this said, however, its presence persists in the modern
world, as is readily detected by the subtle distinction that the
French language makes between “la douleur”—that is, the
somatic nociceptive neuropathic pain—and “les douleurs”—
that variety of spiritual pain and human suffering that is so
widely prevalent throughout the human experience. This more
spiritual version of pain and suffering today is generally
thought of or explained, at least from our clinical perspective,
as having some sort of physical basis. It could just as easily be
explained as being neuropathic or physical at times when there
is even a thorough lack of organic etiological evidence.
Neurosurgery has come to rely primarily on broad categories
of methodology and technique, namely lesioning and neuro-
modulation, to control and lessen the suffering of the pain-
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BROGGI
ridden patient. Both strategies rely on the interruption of
abnormal sensory neuronal activity that might be interfering
with normal higher brain mechanisms. Neuromodulation has
the advantage of being able to be much more precisely anatom-
ically tailored and of being reversible. In neurosurgical centers
throughout the world as well as in our own Istituto Neuro-
logico C. Besta, the implantation of neuromodulation devices is
now being routinely used to treat neuropathic pain of many
different etiologies as well as in many different anatomic sites
with results that range from fair to excellent.
Recent clinical reports that used magnetic resonance imaging
(MRI) and positron emission tomography (PET) functional
imaging techniques have prompted our group at C. Besta to
propose some exciting new anatomic targets on which we
might be able to perform surgery to treat psycho-affective dis-
orders. The results we obtained from these early procedures
have been satisfactory and promising enough for us to pro-
pose that neuropathic pain and psycho-affective disorders may
actually share a common anatomophysiological common path-
way. We have identified this common pathway as Brodmann’s
Area 25, the anterior cingulated gyrus.
These findings lend support to the theory of a neuronal net-
work, an alternative to the Broca-like theory of neuronal struc-
tures, following standard neuronal behavior that may offer a
new kind of understanding to the puzzling phenomena of neu-
ropathic pain and psychoaffective disorders.
We believe that we can now conclude from these findings
that it is reasonable to suggest that both of these disabling dis-
orders may now be managed with complementary or similar
therapeutic strategies that belong to the neurosurgical domain.
This article is aimed to support this hypothesis.
Different Types of Pain
Pain that arises from the activation of a sensory receptor is
known as nociceptive pain. It is easy to understand how this
kind of pain can function as a natural defense in protecting
organisms from hostile environments. Nociceptive pain arises
as the result of a neuronal reflex arc, and it also brings with it
a behavioral or psycho-affective component. When animals feel
pain, they react by either escaping from the alleged source of
their pain or by directing an aggressive response to that source.
When we human beings experience nociceptive pain, we
behave similarly, fight or flight, but with a significant modifica-
tion brought about by cognitive and/or conscious sequelae.
These sequelae run the gamut from experiencing suffering, to
feeling guilty, to feeling angry, and there are even times when
our emotional rage and anger can be directed toward ourselves
and take on unmistakable signs of self-destructive and self-
loathing behavior. When a human being’s psycho-affective
environment is disturbed, as can often happen in the case of
some psychotic patients, there can be times when an individual
actually becomes the cause of their own nociceptive pain and
of their own lesions.
Although these two categories of what may be thought of as
human complications that are secondary concomitants to noci-
ceptive pain are beyond the scope of this discussion, they do
SHC904 | VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT
need to be mentioned because the neurosurgeon must be aware
of the clinical reality. They represent a behavioral extreme that,
not unlike other human behavioral patterns, deviates from
what might be thought of as an appropriate physiological
adaptation. Even more importantly to the clinician, they can
make the lives of psychiatrists, psychotherapists, and neurosur-
geons both difficult and stressful.
Our task in this report, however, will be to deal with the
more common variety of neuropathic pain that so often brings
patients to our consultation office.
Neuropathic Pain
Today, pain is generally categorized as being nociceptive
when it appears to arise as a defense against the environment
and it is universally felt by all species of animals; it is consid-
ered neuropathic when it conforms to the International
Association for the Study of Pain (IASP) definition: that is,
when the pain “is initiated or caused by a primary lesion or
dysfunction of the nervous system.” This definition includes
lesions that occur within both central and peripheral lesions.
This type of pain therefore involves both a behavioral reaction
and an experience of feeling or sensation that arises secondar-
ily to an injury to the central nervous system (CNS). The phys-
ical and psychological reflexes that result can range from a
dysautonomia that we in neurosurgery are able to work with to
a darker, more psychologically complicated variety of CNS
reaction that seems closer to what we think of when we speak
of complications of the soul, which can be impossible for even
the most skilled clinician.
In this scientifically rational moment in history when our
tendency is to rely more on technology than on philosophy,
most philosophers, psychiatrists, and even religious leaders
would probably agree on the view of the so-called mind-brain
problem that without a CNS there can be no soul, no spiritual
feeling, and, for these reasons, no relationship between humans
and God or gods. On similar grounds, it would also seem safe
to assert that there could be no experience of pain without the
CNS. In the case of neuropathic pain, at least, there would seem
to be little doubt that the source of pain was some form of CNS
lesion. Following this kind of logic, there can be little doubt
about how or why neurosurgeons came to wonder whether it
might not be possible to achieve freedom from pain by the sur-
gical strategy of an additional CNS lesion. On the basis of this
logic, it should therefore come as no surprise that the surgical
strategy of lesioning has been used for centuries. Unfortunately,
however, it would not be overstating the case to say that only
short-term and limited success has been achieved, along with
a significant list of unwanted and long-lasting side effects (18).
Psycho-affective Disorders
In the 21st century, the clinical reality of depression has
emerged as one of the leading worldwide causes of disability
and human suffering. More than 121 million people are known
to be suffering from this disease, with the statistics revealing
that it is twice as prevalent in women as in men and increas-
ingly prevalent in young people. There are now more than
www.neurosurgery-online.com

800,000 deaths worldwide attributable to suicide each year, and
there can be little doubt that depression has played a significant
role in this self-inflicted form of mortality.
Obsessive-compulsive disorder (OCD) affects 2 to 3% of the
population and is among the ten most common causes of dis-
ability worldwide. Though medical treatment is widely avail-
able and usually effective for both depression and OCD, the
tendency to relapse and recur is significant in both of these
conditions, and a significant percentage of each is refractory to
current forms of therapy.
Each of these conditions, depression and OCD, was consid-
ered as a precondition for frontal leucotomy by Egas Moniz,
who received the Nobel Prize for his pioneering work in this
area. On the basis of Moniz’s success, it is not surprising that
earlier psychiatrists came to propose neurosurgical lesioning as
a therapeutic approach for patients afflicted by such widely
differing psychiatric disorders as OCD, aggressive behavior,
chronic depression, other diseases such as Gilles de la Tourette,
and many syndromes that lie on the boundary between abnor-
mal movement, pain, and OCD.
After a dark and prolonged period, the field of psycho-
surgery took center stage in a much debated and controversial
way, and it is natural for anyone to doubt that any legitimate
therapeutic potential can be found in neurosurgical treatment
of psychiatric and psychological disorders. Fortunately, how-
ever, that dark period seems to have passed. Backed up by the
remarkable successes of neuromodulation and deep brain stim-
ulation (DBS), particularly in the treatment of Parkinsonian
patients, it is now time to reconsider the potential of neurosur-
gical treatment for a wide range of psychiatric disorders,
including OCD, major chronic depression, and aggressive
behavior of secondary etiology.
PATIENTS AND METHODS
Advantages and Limits of CNS Lesions to Treat Pain:
An Analysis of Earlier Studies
In the past 50 years, technology has yielded many tools that allow
the neuroscientist to study the effects of environmental stimuli on the
activity of the brain’s internal structure. Angiography, for example,
allows the visualization of the brain’s vascular tree and reveals previ-
ously undetectable arteriovenous malformations. If the neurosurgeon
was able to exclude these malformations from the brain’s circulation, it
would seem reasonable to expect a clear-cut evidence-based demon-
stration of cure if there is no other parenteral vascular occlusion (22).
Similarly, CT scans and the use of MRI have enabled the neurosurgeon
both to visualize and to treat brain tumors that could not have been
accessible or so precisely treated in the past. And so, today, when the
neurosurgeon is able to extirpate these previously inaccessible tumors
until there are no signs of any additional tumor regrowth, there is no
reason to assume that the patient has not been cured. Spinal disc
pathology has also been clearly demonstrated with the use of CT and
MRI, and a cure for this condition is now available by surgically free-
ing the patient of that disc-root pathology.
When the neurosurgeon is asked to deal with the subject of neuro-
pathic pain, there has been no clear-cut technology that enables the
caregiver to achieve any signs of an objective or successful therapeutic
NEUROSURGERY
PAIN AND PSYCHO-AFFECTIVE DISORDERS
response. Today, however, functional MRI is now able to show enlight-
ened neuronal volumes that are so-called active, that is, they are meta-
bolically enhanced during specific pain attacks (68). Until now, however,
there has been no therapeutic intervention possible to demonstrate or
achieve any continuous level of neuropathic pain relief. For these rea-
sons, the so-called pain experts have only been able to propose new
drugs and several new surgeries; at least to our knowledge, they have
only been able to evaluate the effectiveness of any drug or surgical
intervention indirectly and by the use of the scientifically suspect strat-
egy of the subjective report, such as the Visual Analog Scale, the verbal
report of the patients (“I am/am not feeling better”), a decrease in drug
intake, and behavioral inventories such as the quality of life. Because of
this problematic situation, the IASP now suggests the following indirect
criteria: success is based on the relief of pain that is greater than 50%
reduction, and an excellent result is based on a 75% reduction.
The analysis of the results of surgeries for trigeminal neuralgia uses a
Barrow Neurological Institute (BNI) score of 1 and 2 (i.e., no pain with-
out drugs). On the other hand, when judging the results in vascular
malformations, such as aneurysms, they are excluded or not by both
endovascular and surgical approaches. A similar situation can be found
in psychiatry when it comes to the treatment of psycho-affective disor-
ders. Though clearly much more often acknowledged in modern
wealthy societies, psycho-affective disorders are known to have existed
in ancient cultures. In the Iliad, Homer chooses to describe the psychically
disturbed individual as a prophet or as being clearly different from those
whose psychological disturbance, irrationality, vindictiveness, jealousy,
or even madness is linked to a king, a warrior, or the gods.
By its very nature, the discipline of psychiatry is, almost always,
forced to rely heavily on indirect reports or the subjective accounts of
its patients to assess the success of their treatment. Strangely enough,
this is very much the way the modern physician is forced to deal with
the subject of pain. It is on the basis of subjective responses like “I am
feeling better or worse” or the patient’s family’s opinion that “he is
doing better” that a physician must often determine the patient’s level
of medication, and so too must neurosurgeons assess the effectiveness
of their pain treatment. Traditionally, psychoanalysts have also had to
rely on indirect behavioral measures, such as the number of visits to
their office, or the patient’s level of boredom, silence, or dissatisfaction,
to determine the therapeutic effectiveness of their treatment. Typically,
these patients are rarely cured.
It is doubtless that as a result of these evaluative problems and lim-
itations that the clinical questions of pain and psycho-affective disor-
ders often seem to be so strikingly similar. The lack of cure in both of
these situations demands that caregivers, whether they are therapist,
neurosurgeon, neurologist, psychiatrist, or psychoanalyst, must always
rely heavily on his or her own subjective feelings and those of their
patient when determining the patient’s well-being. This obvious intrin-
sic inability to make an objective determination or demonstration of
cure makes all of these fields vulnerable, in one way or another, to the
quack, the charlatan, and the outright criminal eager to prey on the
unrelieved suffering of fellow human beings.
Not surprisingly, those professionals who rely heavily on so-called
alternative therapies, many of which originate in the East and are being
widely practiced in the West, rarely speak of curing pain and almost
always speak of relieving pain. They make heavy use of strategies like
acupuncture and alternative behavioral approaches like meditation and
visualization, the thrust of which is directed towards controlling the
mind. Because there are no cures for neuropathic pain or for psycho-
affective disorders, each of these two tragic human pathological situa-
tions takes on a quality that, in comparison to other medical conditions,
might be described as being the equivalent of the dark side of the med-
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BROGGI
ical moon. They are clearly there; people are undoubtedly suffering
greatly from these situations, yet there is, more often than not, very lit-
tle that medicine is able to do to achieve the kind of cure and cure rate
that most modern physicians have become accustomed to experiencing.
This unfortunate clinical reality is further complicated by the fact
that the patient who is experiencing neuropathic pain has the addi-
tional tendency to become depressed, particularly when the imaging
morphological studies that have become the security blanket of
Western medical technology fail to demonstrate any objective correlate
to account for the patient’s distress. Not surprisingly, this diagnostic
failure prevents both the family and the larger society from both under-
standing and being sympathetic to these patients’ tragic plight. More
often than not, the logic that follows is usually that nothing is wrong if
nothing shows up in an MRI. The patient must suffer not only his or
her own physical pain, but also the additional discomfort and pain of
becoming marginalized as a hypochondriac or a chronic complainer,
and consequently an unwelcome alien.
RESULTS
Towards a Positive Resolution from the Anatomic-
neurosurgical Point of View
Anatomy has made it quite clear that there are pathways
from the sensory receptors to the cortex that are responsible for
higher cognitive functions, and that these pathways have spe-
cific characteristics (i.e., the Broca-like approach). There is noth-
ing more rewarding for a neurosurgeon than to be able to
relieve a patient from the suffering of chronic unilateral somatic
pain by performing a successful percutaneous cordotomy.
Unfortunately, however, the problem will often return in a few
months, provided that the disease does not kill the patient. The
theoretical foundation for this type of surgery is obviously the
anatomic understanding of the fiber pathways transmitting the
pain from the receptors to high neuronal structures such as the
cortex, in which Broca’s concept accounts for the defined site of
functions—motor, sensory, etc. Much of the confusion sur-
rounding the surgical therapeutic approach for nociceptive
pain, which can be successful, and of neuropathic pain, which
is seldom successful, is derived from this vision. In neuropathic
pain, the neuronal message is believed to run in long neuronal
pathways, fibers, and nuclei. This theoretical foundation has
resulted in the sequelae of lesioning in the spinal cord (cordo-
tomy, myelotomy, commissurotomy) and in the brain itself
(with tractotomies and lesions of subcortical nuclei) without
any enduring positive results. It is as if pain is an enemy that
is wounded, but then retreats, disengages from the fight, and
moves to a higher level, which is accounted for, in Broca’s the-
ory, by the fact that human beings are standing bipeds. This
movement towards the cortex is thought to be necessary and
even indispensable for those higher functions that allow for
cognitive and emotional elaboration with, of course, their recip-
rocal relationships with subcortical structures, such as basal
ganglia, thalamus, mammillary bodies, etc. This particular
retreat-and-reassemble view of the way chronic pain responds
to lesioning strategies seems to bear a striking parallel to what
history teaches us about the historical failures of such conquer-
ing heroes as Alexander the Great and Napoleon. This recurring
SHC906 | VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT
pattern and apparent logic for persistent failure suggest a need
for a new approach and a new kind of strategy, one that is more
diplomatic and, more importantly, persistently successful. We
believe that neuromodulation may be that alternative.
This new approach, however, seems to suggest a rethinking
of our understanding of pain, one that grows out of the idea
that pain may very well be the result of a perturbation in com-
plex neuronal networks that link the experience of pain with
feelings of affect, such as passion, rage, madness, and extreme
religiosity, along with an obvious cognitive involvement.
Following the logic of the earlier, more traditional, approach
to pain, the idea was to target therapeutic interventions toward
the affective side of the pain, with the result being that psychi-
atry turned more to strategies like electroconvulsive therapy
(ECT) that were then being used for other psychiatric disorders.
It wasn’t long before pain therapists began to propose ECT for
the treatment of pain, particularly when the secondary affective
sequelae became the primary clinical feature. At another ther-
apeutic extreme, people began to use hypnosis as well (108).
It is somewhat ironic that the knowledge gained from the
clinical phenomenon of psychosurgery, for all of its limitations
and problems, has made a significant contribution to our under-
standing of pain mechanisms. It was Freeman and Watts (37)
who modified the title of the 1948 edition of their 1942 mono-
graph dealing with frontal leucotomy by adding the qualifying
phrase, “in the treatment of mental disorders and intractable
pain.” In that edition, they made the prescient comment that
“probably the most important discovery is that unbearable pain
can be favorably influenced by lobotomy” (37).
On the basis of these early, preliminary observations, many
investigators have sought to treat chronic pain by using lesions
that were targeted to the frontal lobes (52) and to the Papez cir-
cuit. The anatomic structures in which chronic pain and affective
disorders seem to overlap became the targets for stereotactic
radiofrequency lesions that were being performed to treat
intractable pain syndromes (Fig. 1). In the past, lesioning strate-
FIGURE 1. Illustration of the electrode used to perform radiofrequency
lesions. When the electrode reached the estimated target, it was rotated (1)
to allow the collateral to be extruded (2) and to perform the radiofrequency
lesion (3) laterally to the tip. The electrode’s rotation allows it to reach mul-
tiple targets.
www.neurosurgery-online.com
 PAIN AND PSYCHO-AFFECTIVE DISORDERS

TABLE 1. Lesions of the sensory pathwaysa

Thalamic VPM-VPL nuclei
Mesencephalic lemniscal pathways
Trigeminal tractotomy
Anterolateral cordotomy at C1
Medial commissural cordotomy at C1
Medial commisurotomy at lumbar level
Rhizotomy everywhere, cranial and spinal
DREZ, fiber lesions
Peripheral neurotomy
a
VPM, ventral posteromedial; VPL, ventral posterolateral; DREZ, dorsal root entry FIGURE 2. X-ray showing the electrode introduced in
zone. the pulvinar target point (Reprinted from, Siegfried J:
Stereotactic pulvinarotomy in the treatment of intrac-
table pain, in Krayenbuhl H, Maspes PE, Sweet WH
gies were used primarily when it was thought that an interrup- (eds): Progress in Neurological Surgery. Basel,
tion in the neuronal activity of an intervening pathway might Karger, 1977, vol 8).
interfere with the more rostral brain structures that were believed
to be playing a part in the involved pathology (Table 1) (108).

Lesion of the Centromedian-parafascicular Complex

in the Medial Thalamus
The targets were center median, parafascicular, and intralam-
inar nuclei, which were thought to receive input from the
spinothalamic system and the periacqueductal reticular forma-
tion. Atypical facial pain, causalgia, and failed back surgery
syndrome had beneficial outcomes from this procedure. We
observed no sensory impairments after unilateral thalamotomy,
such as are usually observed after cordotomy and tractotomy,
where the results were almost always short-lived (44).
Lesion of the Pulvinar
The pulvinar receives input from the dorsal columns and
the anterolateral system and projects to the frontocentral cortex.
Unilateral pulvinotomy (Fig. 2) has been performed with var-
ied results in cases of cancer pain and benign pain; the results
did seem to be better for cancer pain than for other chronic
pain, although the pain control was short lived. Pulvinar pro-
cedures resulted in few side effects, although numbness, confu-
sion, and aphasia have been described. Bilateral pulvinotomy
did not increase the risks or the improvement rate (56).
Lesion of the Midbrain (Midbrain Tractotomy)
Midbrain tractotomy comprised physical or radiofrequency
sectioning of the spinothalamic tract (Fig. 3), which results in
contralateral analgesia, loss of temperature perception, and the
preservation of light touch and proprioception. The risk of
complications was significant, and it is difficult to make state-
ments about its effectiveness on the basis of what is found in
the literature (5).
Lesion of the Anterior Cingular Cortex
The cingulate gyrus is part of the medial (Papez) limbic
loop, and it plays a role in pain perception and sensation,
FIGURE 3. Pathological specimen of an open midbrain
tractotomy (Reprinted from, Gorecki JP: Stereotactic
midbrain tractotomy, in Gildenberg PL, Tasker RR
(eds): Textbook of Stereotactic and Functional
Neurosurgery. New York, McGraw-Hill, 1998).
although the exact nature of the mechanism is still being
debated. Cingulotomy was performed for some psychiatric
patients who were unresponsive to medications, and this
approach was subsequently adapted to treating pain, includ-
ing cancer pain, of a skeletomuscular origin. The anterior por-
tion of the cingulate gyrus was the target (Fig. 4), and the long-
term effects were disappointing, although the pain control was
almost immediate (29).
Lesion of the Posteromedial Hypothalamus
The hypothalamus is a central node of the Papez circuit, and
it is connected with the hippocampus, amygdala, and limbic
thalamus. In 1970, Sano et al. (86) described stereotactic radiofre-
quency lesions within the ipsilateral posterior hypothalamus to
treat patients affected by either disruptive behavior or pain (Fig.
5). Temporary pain relief was found to be limited, with recur-
rence of pain taking place in half of the patients over a duration
of approximately 6 months.

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BROGGI

FIGURE 6. X-ray showing the

correct position of the needle used
to perform a percutaneous cervical
cordotomy (Reprinted from,
Kanopolat Y: Percutaneous cervi-
cal cordotomy for persistant pain,
in Gildenberg PL, Tasker RR
(eds): Textbook of Stereotactic
FIGURE 4. Postoperative magnetic resonance imag- and Functional Neurosurgery.
ing (MRI) scan showing the effect of the lesion in the New York, McGraw-Hill, 1998).
center of the cingulated gyrus (Reprinted from,
FIGURE 5. Posteromedial hypo-
Hassenbusch SJ: Cingulotomy for cancer pain, in
thalamotomy. Note the lesion just
Gildenberg PL, Tasker RR (eds): Textbook of inquiry that is fraught with
lateral to the left mammillothala-
Stereotactic and Functional Neurosurgery. New considerable confusion. With
mic tract (Reprinted from, Sano
York, McGraw-Hill, 1998). that said, this theory, more
K: Intralaminar thalamotomy
(thalamolaminotomy) and postero- than any other, has opened
Trigeminal Tractotomy medial hypothalamotomy in the the door to the idea that the
treatment of intractable pain, in kind of electrical interference
Trigeminal tractotomy, first performed in 1937 by Sjoqvist Krayenbuhl H, Maspes PE, Sweet of the CNS that we know of
(96), was found to result in ispsilateral thermoanalgesia of the WH (eds): Progress in Neuro-
as neuromodulation may be
face with preservation of other sensory functions. The opera- logical Surgery. Basel, Karger
able to achieve a positive
tion could be performed either by open surgery or stereotati- 1977, vol 8).
effect on the treatment of pain.
cally (51), and the reported results were found to be good both
in patients with post-herpetic neuralgia and in patients with Psychosurgery Lesions
cancer pain. The complications that followed these procedures,
such as ataxia, paralysis of vocal cords, gait impairment, and The treatment of mental disorders by means of brain surgery,
contralateral analgesia, were frequent, particularly in the open the so-called “controversial” field known as psychosurgery,
surgery series. was predicated on the idea that an improvement of psychiatric

Cervical Cordotomy
Percutaneous anterolateral cordotomy at C1-C2 level and
medial commissural cordotomy at C1 were indicated for
intractable pain in patients with terminal disease (Fig. 6) (74).
Severe complications, such as respiratory impairment and motor
and sphincter paralysis were reported, however.

Dorsal Root Entry Zone Fiber Lesions

The procedure involves a microsurgical incision at the
entrance of the rootlets into the dorsolateral sulcus of the spinal
cord along the tract selected to treat pain (Fig. 7) (94). The pro-
cedure should selectively lesion the nociceptive fibers that are
found laterally in the dorsal rootlets. Cancer pain, neurogenic
pain (i.e., brachial plexus injuries, spinal cord lesions, periph-
eral nerve injuries), and spasticity that is accompanied by pain
FIGURE 7. Postmortem specimen of spinal cord after
all benefit from this procedure. When good results are observed
a bilateral dorsal root entry zone (DREZ) (Reprinted
in most of the reported series, they are almost always of a tran-
from, Iskandar BJ, Nashold BS Jr: Spinal and trigemi-
sient nature. nal DREZ lesions, in Gildenberg PL, Tasker RR (eds):
Of all the theories that have appeared in the physiology lit- Textbook of Stereotactic and Functional Neuro-
erature, it seems that only Melzack and Wall’s Gate Hypothesis surgery. New York, McGraw-Hill, 1998).
(71) has been able to bring any persistent new light to a field of

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symptoms could be achieved by removing or lesioning spe-
cific brain tissue.
The ideas underlying psychosurgery have a long and endur-
ing history that, if we are to draw the conclusions, probably has
prehistoric origins, from human skulls with holes in archaeo-
logical findings of Neolithic humans. It is certainly possible that
during this prehistoric time surgeries were performed for pur-
pose of liberating spirits, demons, and other supposed causes of
illness and human suffering.
The field of modern psychosurgery seems to have begun at
the end of the 19th century with Swiss surgeon Gottlieb
Burckhardt, who performed bilateral cortical resections in a
series of patients with mental illness (43). Burckhardt’s report,
along with several other anecdotal reports, when combined
with advances in anesthesia and technological progress in con-
ventional neurosurgery, made it possible to perform neurosur-
gical approaches that were previously impossible.
Frontal Leucotomy and Cingulotomy
Frontal leucotomy involves an injection of alcohol into the
brain that is aimed at destroying the fiber tracts that connect the
frontal lobe with the rest of the brain (73). It was originally
introduced for the purposes of treating schizophrenia and
related psychiatric disorders, but it was subsequently employed
to treat a wide range of psychiatric diseases. Years later,
Freedman and Watts proposed a modification of this kind of
frontal leucotomy that become known as the prefrontal lobot-
omy (37). All of these procedures were associated with a high
incidence of side effects and complications that included intel-
lectual impairment, personality changes, seizures, paralysis,
and, in some cases, death.
As described previously, the procedure known as cingulo-
tomy is based on the destruction of the anterior portion of the
cingulate cortex. Cingulotomies, along with frontal leucotomy
were used to treat various forms of psychiatric symptoms.
The success rates were similar to earlier psychosurgeries,
although there was a noticeable reduction in side effects and
complications.
Anterior Capsulotomy
Anterior capsulotomy consists of lesions generated by ther-
mal damage or focal gamma radiation of the fibers that pass
through the anterior portion of the internal capsule. These
fibers encompass the tracts that connect the ventromedial and
orbitofrontal cortex and anterior cingulate gyrus with the thal-
amus, amygdala, and hippocampus (21). This surgical proce-
dure has been used to improve the symptoms that accompany
several psychiatric diseases, including anxiety, agoraphobia,
major depression, and OCD.
Amygdalotomy and Posterior Hypothalamotomy
In these procedures, bilateral radiofrequency lesions of either
the amygdalae or the posterior nuclei of the hypothalamus are
performed in the treatment of medically intractable aggressive
behavior and epilepsy (30, 87). The destruction of both amyg-
dalae in monkeys induced a specific syndrome that was
NEUROSURGERY
PAIN AND PSYCHO-AFFECTIVE DISORDERS
described by Kluver and Bucy in the late 1930s. Several years
later, the human counterpart of this Kluver-Bucy syndrome was
described (30). Kluver-Bucy syndrome consists of a loss of
aggressive behavior and fear responses, psychic blindness, oral
exploration of objects, and hypersexuality. Amygdalotomy may
induce a marked reduction in the patient’s level of emotional
excitability, a normalization of adaptive social behavior, and a
reduction of seizures.
On the other hand, the Japanese neurosurgical team lead by
Sano has reported success in controlling violent and restless
behavior after the bilateral destruction of the posteromedial
hypothalamus in nearly 85% of patients (87).
Subcaudate Tractotomy
This procedure, first developed by Geoffrey Knight (53), con-
sisting of lesions placed in the white matter of the substantia
innominata below the head of the caudate nucleus, has been
used for the treatment of major depression, OCD, and anxiety
disorders. Modest success was reported in the one-third of the
patients who reported beneficial effects (97).
Thalamic Nuclei
Several thalamic nuclei have been targeted for lesions aimed
at improving psychiatric symptoms. Of all of these strategies,
only those directed at the center median (CM) nucleus, the dor-
somedial (DM) nuclei, and the anterior nuclei seem worthy of
mentioning. Thalamotomy has been performed for epilepsy,
aggression, and automutilation in mentally retarded patients.
Medial thalamotomy has also been performed in two patients
with terminal anorexia (112). Both of these patients have
regained weight, and they have improved significantly in terms
of their OCD symptoms and quality of their life. Of all the
above-mentioned procedures, the only one to survive the
strong criticism that has been directed at the entire field of psy-
chosurgery (66) is cingulotomy, which has been validated by an
independent cooperative study by Ballantine et al. (8).
Nowadays, stereotactic or radiosurgical cingulotomy is still
being used to treat selected cases of chronic pain, such as that
of failed back surgery syndrome, when drugs and restorative
surgery have been ineffective. However, in the wake of psy-
chopharmacological and psychoanalytical advances, the strat-
egy of lesioning brain structures to reverse psychiatric symp-
toms has been almost completely dismissed. Nevertheless, the
demise of lesioning strategies seems to have ushered in a new
era of safer and thoroughly reversible procedures such as
spinal cord stimulation (SCS), deep brain stimulation (DBS),
and motor cortex stimulation (MCS).
Neuromodulation
The Treatment of Pain
When the idea of neuromodulation was first proposed, it
seemed to be the reasonable answer to a tailored, reversible
therapeutic alternative that would be able to interact with struc-
tures of CNS that were responsible for the cause of pain (2, 20,
42, 45, 55, 62, 80, 111). In many ways, neuromodulation
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BROGGI
approaches the ideal Aesclepian strategy in that it neither causes
damage to the patient nor worsens their condition in any way.
The discovery of endogenous systems that are able to control
pain and its perception has focused the neurosurgeon’s interest
on the medial brainstem (periventricular gray-periaqueductal
gray) and the nucleus raphe magnum (4). Coincidentally with
these discoveries, interest in the limbic system seems to have
been slightly abandoned.
This renewal of interest in using neuromodulation to treat
mental diseases and its fostering of exciting new ideas about
brain functions and interlaced networks have brought about
the reconsideration of targets that act as nodes in the limbic net-
work (100). The chronic stimulation of the posteromedial hypo-
thalamus based on fMRI results (68) has been demonstrated to
benefit facial pain bouts in cluster headache (59) and impulsive
behavior in aggressive patients (35). Behavior and pain have
been found to overlap in the nucleus accumbens when it is
stimulated to treat OCD (99) and for neuropathic pain in the
septal area (91). Electrodes have been implanted to treat cancer
pain in the centromedian-parafascicular (CM-pf) complex (106),
and vagal nerve stimulation (VNS) has recently been used to
treat major depression and some refractory headaches, includ-
ing cluster headache (67), in which pain, behavior, and auto-
nomic responses are strictly linked.
The chosen targets are similar to those that have been used in
the past, and perhaps today, for lesioning. The short-term
results have been excellent, and the medium- and long-term
results have been fair, as indicated by the reported 60% reduc-
tion in pain.
The best treatment seems to be the passage of time—aging—
and the course of the primitive disease. These facts may
account for the excellent results that have been obtained with
drugs and surgery in treating cancer pain that consists of a
mixture of pain in which the nociceptive component predomi-
nates over its neuropathic counterpart and for which there is an
unfortunately short survival time.
Nearly Three Decades of Neuronavigating
against Pain and Suffering
The years between 1980 and 2007 have been years of extraor-
dinary progress in the field of chronic brain implantation.
During this time, the literature has welcomed a rich body of
experience from neurosurgical centers around the world.
During this time, our group at the Istituto Neurologico C. Besta
has been busily involved in implanting thousands of neu-
rostimulation devices into the nervous systems of patients who
were suffering from a variety of different painful conditions
and syndromes (Table 2). A brief description of the clinical
results we have obtained by different treatment modalities is
reported below.
Since the performance of our first spinal cord stimulation
procedure, we have achieved a long-term success rate that
ranges from 18 to 86% (77). We have implanted SCS devices in
476 cases, achieving a fair to good level of success in treating
neuropathic pain, painful paraplegia, multiple sclerosis, and
familiar spastic paraparesis. We have also obtained good results
SHC910 | VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT
TABLE 2. Neurostimulation procedures performed at Istituto
Neurologico C. Besta
Type of stimulation Cases
Spinal cord stimulation 476
Trigeminal nerve stimulation 21
Peripheral nerve stimulation 5
Thalamic stimulation 24
Occipital nerve stimulation 8
Hypothalamic stimulation 27
Internal capsule stimulation 1
Motor cortex stimulation 16
Total 570
when treating patients with peripheral vascular disease and
sympathetic reflex dystrophy syndrome (16).
The efficacy of stimulating the trigeminal nerve (Fig. 8) contin-
ues to remain controversial, primarily because some authors
have reported poor results while others have reported good
long-term results (14). At our institute, trigeminal nerve stimula-
tion has been used in 21 cases in patients with a mean age of 67
years. After a trial period that ranged from 7 to 24 days, stimu-
lation was ineffective in four post-herpetic patients and in three
painful anesthesia patients. For this reason, the implanted elec-
trodes were removed. Pain relief has been achieved in 14 cases,
however, and all patients continue to control their pain via their
implants after 18 months. In one of these patients, the beneficial
effect continues after a post-implant time of three years (14).
Using peripheral nerve stimulation, we have achieved a 60%
success rate when treating reflex sympathetic dystrophy (109).
We have implanted neurostimulating devices (Fig. 9) in five
patients, and a good level of pain relief has been obtained in
four of these five patients for a prolonged duration that ranged
from 5 to 7 years (17).
Poor long-term results were obtained with DBS in the control
of pain; for this reason, DBS has been largely abandoned during
the last decade (20). According to several authors, however, the
FIGURE 8. Postoperative x-rays showing the placement of the quadripo-
lar stimulating leads close to the trigeminal ganglion.
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control of nociceptive pain
has been achieved in 20 to
81% of cases treated with DBS
(83). On the other hand, the
success rate achieved in con-
trol of neuropathic pain has
been reported to be 26 to 72%
of treated cases (83). We have
used 24 DBS leads implanted
in the ventral posterior lateral
thalamus, the CM-Pf complex
(Fig. 10), or periventricular
gray matter. Fifteen leads
were directed towards con-
trolling central pain, and
nine leads were directed
towards the control of vari-
ous types of neuropathic
pain. We observed that pain
symptoms improved soon
after implantation, although
we did observe the develop-
ment of a long-term toler-
ance that prevented further
improvement (15).
Internal capsule (IC) stimu-
lation has been typically indi-
cated for the treatment of post-
stroke pain because it is less likely to induce sensory loss (84).
According to the literature, IC neurostimulation has been found
FIGURE 10. Postoperative MRI scan displaying the deep brain stimula-
tion (DBS) electrode tip in the right centromedian-parafascicular complex
of the thalamus.
NEUROSURGERY
FIGURE 9. Postoperative com-
puted tomographic scans showing
the placement of the quadripolar
stimulating leads adjacent to the
tibial nerve.
PAIN AND PSYCHO-AFFECTIVE DISORDERS
FIGURE 11. Postoperative three-dimensional reconstruction showing the
placement of the motor cortex-stimulating electrode lying over the surface
of the primary motor cortex in a patient with neuropathic pain.
to relieve pain, either completely or partially, in almost 60% of
treated patients (31). One of our patients who was suffering from
post-stroke pain and spasticity was implanted with a DBS lead in
the posterior limb of IC, and we observed an improvement in the
associated spasticity that turned out to last for more than 5 years,
paralleling a comparable long-term relief of pain (31).
Motor cortex stimulation has achieved a 75% success rate in
controlling deafferentation pain and a 50% success rate in
improving the symptoms of thalamic and suprathalamic pain
(101). Motor cortex stimulation (Fig. 11) has been used in six
patients suffering from neurogenic pain (thalamic syndrome and
vascular lesion of the brainstem) (Fig. 12) and in 10 patients with
neuropathic pain (facial pain with different etiologies) (76, 102).
Our best results, however, were obtained in the treatment of neu-
rogenic pain, where we were able to achieve a 60 to 80% reduc-
tion in pain. When it came to the treatment of neuropathic facial
pain, however, we were only able to achieve a reduction of
around 40 to 50%. Interestingly enough, MCS has prompted this
remarkable decrease of pain along with a concurrent reduction of
dystonia and reduction of rigidity in the thalamic hand in four of
the five patients who received implants primarily to improve
their movement disorders (32, 34).
There are only a few reports in the literature describing
occipital nerve stimulation for the relief of pain, and what has
been found is a 60% reduction of chronic cluster headache
(CCH) (19, 64). We have implanted electrodes in the occipital
nerve in eight patients suffering from CCH (Fig. 13), but we
were able to report that only one patient was pain-free after 12
months of treatment. One of these patients was able to obtain
a fair level of pain relief and is now awaiting a DBS implant.
Five patients were relegated to DBS because of poor results,
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BROGGI
FIGURE 12. Postoperative three-dimensional recon-
struction in a patient with post-stroke pain. The elec-
trode crosses the primary motor cortex (yellow). The
active contacts (red crosses) are stimulating the hand-
knob area.
and the electrode had to be removed because of complications
from an infection in one patient (60).
Posterior hypothalamus DBS represents a promising
approach for the treatment of CCH by using DBS (Fig. 14). In
addition to our earlier studies (33, 57, 58, 59), others have
reported more than 50% of their treated patients as having ben-
efited from this approach (90, 98). We implanted 18 leads in 16
patients in which a mean follow-up time of 23 months was
conducted. Ten of these patients have reported being com-
A ing (SUNCT) described his severe intractable pain as being
B
FIGURE 13. A, stimulating leads lying over the great occipital nerve. B,
Postoperative x-ray scans showing the placement of the electrode.
SHC912 | VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT
FIGURE 14. Diagrams showing the position of several
subcortical nuclei compared to the third ventricle (pale
and deep gray). The red line displays a typical trajec-
tory calculated to reach the posterior nucleus of the
hypothalamus (red dot). A, coronal section; B, sagittal
section. GP, globus pallidus; PHyp, posterior hypothal-
amus; STN, subthalalmic nucleus; Th, thalamus.
pletely pain-free, and several others have described beneficial
pain relief that has lasted for 4 years. Six of these patients have
described a reduction in their daily bouts and reported experi-
encing only sporadic attacks (33, 57, 58, 59). Remarkably, the
first patient we reported on using short-lasting unilateral neu-
ralgiform headache attacks with conjunctival injection and tear-
well controlled when continuous stimulation of the posterior
inferior hypothalamus was applied (61).
In addition to the work we have done in treating CCH and
pregnancy-induced hypertension, we have also found that DBS
has can be quite useful in the relief of several different types of
pain, including the facial pain that occurs in multiple sclerosis
(five patients), in atypical facial pain (three patients), and in
essential trigeminal neuralgia (one patient). In two patients suf-
fering from multiple sclerosis, we have been able to achieve a
thoroughly pain-free/drug-free status. Three of these patients
have improved to such a level that they felt that their pain was
completely controlled when combined with their pain medica-
tion. In addition, each of these patients was found to need
reduced levels of pain medication after stimulation was found
to produce its results. To date, we have been able to sustain
these beneficial effects for an average duration of 23 months.
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FIGURE 15. Postoperative coronal three-dimensional
reconstruction showing the bilateral placement of the
DBS leads in the nuclei accumbens in an obsessive-
compulsive disorder (OCD) patient.
Neuromodulation for Psycho-affective Disorders
Today, psychiatric problems like OCD, bipolar disorder,
and major depression, once restricted to the clinical domain
of psychiatry, are now being increasingly treated by neuro-
modulation neurosurgery. Metabolic correlational studies
appear to be a good predictor of cingulotomy success in the
treatment of major depression (25), and these positive results
suggest that DBS may prove to be effective in the manage-
ment of this pathology.
Similarly, subcaudate tractotomy has resulted in a 50%
improvement for OCD, a 63% improvement rate when used to
treat anxiety disorders, and a 68% rate when treating affective
disorders with a rate of only 7% when it comes to bringing
about the side effect of unwanted personality changes. These are
all suitable targets for DBS, particularly when this strategy’s
basic reversibility and the ability to carefully tailor the parame-
ters may greatly help to avoid unwanted side effects. Similar
results have also been reported with limbic leucotomy (9).
Modern approaches that now use DBS are beginning to
demonstrate a fascinating potential for controlling disease and
ameliorating symptoms. The rationale for the choice of the fol-
lowing targets for treating OCD and major depression derive
from the work that has been done using PET and fMRI studies
(69, 88). Indeed, the work of Nuttin et al. (79), Sturm et al. (99),
Gabriëls et al. (40), Abelson et al. (1), and other investigators (6,
7) suggest that anterior limb of the IC may be the most likely
target for treating OCD. The same target emerges from the
work of Kopell et al. (54) for treating depression. Mayberg et al.
(70) and other investigators (85) suggest the subcaudate cingu-
late gyrus as a likely target for treating depression, but Velasco
indicates that the inferior thalamic peduncle may be a useful
target for treating OCD as well as major depression (48, 49).
When it comes to the treatment of Tourette’s disease, Visser-
NEUROSURGERY
PAIN AND PSYCHO-AFFECTIVE DISORDERS
FIGURE 16. Snapshot from the software designed to calculate the tridi-
mensional coordinates of the nucleus accumbens (gray dot) in an OCD
patient. Red dot, anterior commissure; blue dot, posterior commissure;
yellow dot, commissural midpoint.
Vandewalle et al. (103), Maciunas et al. (63), and Slavin (per-
sonal communication) propose the median thalamic nuclei as
the most likely target. On the other hand, Servello et al. (93)
have recently reported that the CM and globus pallidus interna
(GPi) might be the most successful target. We found good
results when using GPi stimulation in two cases. Placing our
leads in the nucleus accumbens (Figs. 15 and 16) seems to offer
a promising approach for the treatment of OCD symptoms as
well as for Tourette’s syndrome (27). The nucleus accumbens
along with the ventral olfactory tubercle, the ventral caudate,
and the putamen all collectively form the ventral striatum,
which is part of the ventral continuation of the dorsal striatum.
The majority of patients seem to tolerate DBS quite well, and
marked improvements have been observed and reported in
mood, anxiety, and OCD symptoms (78, 79, 99). A few compli-
cations have been described, including seizures, transient
hypomanic episodes, and worsening of depression and OCD,
when DBS is stopped because of battery failure (41). We have
implanted leads in the nucleus accumbens in two OCD patients
with promising results after a 6-month period of chronic, 24
hour/day stimulation. Similarly, we have recently attempted to
treat a psychiatric disorder by implanting stimulating leads in
various neuroanatomic districts in the hope of resolving the
symptoms of medically refractory aggressive behavior. Three
patients who were struggling with hyperaggression and impul-
siveness that had become resistant to all medical and occupa-
tional therapies have shown a prolonged, 3-year benefit from
the bilateral high-frequency stimulation of the posteromedial
nucleus of the hypothalamus (35, 36). The electrodes were
placed according to the coordinates that have been described
by Sano et al. (87). All three of these patients showed a signifi-
cant reduction in aggressive behavior along with an improve-
ment in social behavior.
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BROGGI
It appears that the only targets that seem to interfere with
psychiatric disorders such as aggressive behavior (the posterior
hypothalamus) and OCD (nucleus accumbens) might also be
suggested as sites that will also interfere with the processes
that regulate pain control.
fMRI studies (69, 70, 92) indicate that the final common path-
ways of both of these targets is Brodmann’s Area 25, the ante-
rior cingulate gyrus.
VNS has been approved for the treatment of refractory
depression and bipolar disorder in Europe and Canada since
2001, which indicates that this form of brain stimulation shows
promising results as an effective neurological antidepressant
treatment. More recently, an alternative to VNS has been pro-
posed for the treatment of major depression which involves
the neurostimulation of deep cerebral areas such as the white
matter adjacent the corpus callosum, Brodmann’s Area 25 (69),
and the nucleus accumbens (89). Both approaches seem to be
clinically effective in almost all patients, with no complications
and seemingly no major side effects.
In conclusion, it seems that these positive outcomes are
quite encouraging, although the limited number of cases
treated and met with success in different centers and with
limited follow-up suggests at least a modicum of caution.
Nevertheless, the anecdotal testimony of an increasing num-
ber of neurosurgeons suggests significant interest in this new
indication of neuromodulation.
DISCUSSION
When Sigmund Freud first described psychic balance, he
stated that normality involves the ability of human beings to
approach pain with different modalities of response. He indi-
cated that the maintenance of equilibrium involves multiple
answers to the unique response that generates pain (38). In the
psychodynamic Freudian approach, pain involves separation
and loss, and the “disease” of pain appears secondarily to a
breakdown of the psyche’s defense system. Pain, in Freud’s
view, is therefore a consequence of a psychic disturbance and
not vice versa; for this reason, the main purpose of psycho-
analysis is to deal with psychic pain (75).
On the other hand, neuromodulation does not seem to inter-
fere with any one precise point or site within the nervous system.
SCS seems to interfere with all the neuronal messages running
through the spinal cord, with the main effect being on ascending
pathways. In choosing a target site for SCS, the level is chosen on
the basis of affecting the wide area that is affected by pain.
Confirmation of the correct placement of electrodes is inferred by
a combination of the clinical response and the verbal report from
the patient that the painful area of the body is covered by pares-
thesias, which are sometimes reported as being pleasurable or, at
worst, painful. In this case, the intent of the stimulation is to
interfere with the patient’s internal environment from which the
pain experience seems to be arising. It is the goal of modulating
his response to an organic cause that is often identified in the
temporal consequences of some as-yet-unidentified interaction
or lesion of the patient’s nervous system.
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When neuromodulation is applied to a peripheral nerve, the
results are typically not very enduring (14). This observation
may, however, be brought into question by the recent report of
subdermal stimulation (G. Barolat, personal communication) in
which nerve fibers departing from receptors are involved. Our
experience in using DBS to treat Parkinson patients has made it
perfectly clear that a precise positioning of the stimulating elec-
trode is crucial. Although we are, at best, only able to suggest a
hypothesis to explain the physiological basis of our success—
that is, the mechanism by which our electrical stimulation
brings relief to the Parkinson patient—it does appear that there
is some form of inhibitory activity, whether this occurs by
increasing inhibitory synaptic activity, interfering with a node of
some neuronal network, or through some as-yet-unknown neu-
ronal mechanism. In light of the results of recent imaging PET
and MRI studies, this kind of a mechanism seems to be most
plausible explanation.
At present, depression is one of the major causes of disabil-
ity and suffering in the world. In biological or psychophysio-
logical terms, depression could be considered as a deviant
response of an individual to its environment, as some kind of
neurological epiphenomenon, possibly an altered status of
synapses producing neurotransmitters and neuromodulators,
or as the result of some damage or dysfunction in the reuptake
mechanism that occurs within the synaptic clefts. Although
psychiatry will doubtlessly come up with its own theories and
hypotheses, there is good reason to expect that this genome-
rich era will produce genetic explanations that will ultimately
confirm what our imaging studies have already demon-
strated—that the CNS is modifying its metabolism in response
to pharmacological stimulation and that the imaging of a
patient suffering from pain and psycho-affective disorders is
quite different from that of a healthy human being.
Finally, it seems apparent from these studies that neuromod-
ulation or, more accurately, DBS is not acting on a single neu-
ron; rather, it achieves its effect on a cluster or clusters of neu-
rons, which then may affect other clusters of neurons in ways
that are far more complex than the kind of simple excitation
and/or inhibition to which we are accustomed.
When dealing with psychiatric disturbances or problems,
every therapeutic intervention takes on profound ethical sig-
nificance that is far more heightened than we in neurosurgery
are accustomed to experiencing. In the past, the most impor-
tant side effect of lesioning was the possibility of evoking a
potentially irreversible change in personality. Fortunately,
neuromodulation and DBS need not be so heavily burdened
by this unfortunate outcome because of its reversible nature.
Nonetheless, one of the most important rights of our patient
is the need for them to be informed about the implications
and outcomes of any particular therapy: its positive thera-
peutic perspectives, possible negative side effects, and mor-
bidity. When dealing with pain and psycho-affective dis-
orders, the patient should always have the privilege of
interrupting the therapy at his will and at any time, even
though neuromodulation has the reversible characteristic that
lesioning lacks.
www.neurosurgery-online.com

Wittingly or unwittingly, virtually every human psyche
drives itself toward a healthy balance of pain and pain-filled
interactions. Human beings seem to have a specific predilection
to introducing pain into daily life, not to mention the
omnipresent obligations and conflicts which enable us to hold
those we love as hostages of their guilt-ridden pain. Our human
potential for a wide array of self-negating, self-inflicting, and
ultimately self-destructive strategies is discomforting. We do
know that the so-called hypothalamic animal will utilize the
capacity of its brain circuitry in such a way that will translate a
sense of danger into fight or flight behavior. On the other hand,
we also know that human beings have the neuronal capability
that lifts writers, artists, theologians, psychiatrists, and neuro-
surgeons to heights of performance and to new levels of energy
that allow them to consistently sustain others while finding
their own professional and existential raison d’être.
We may not be able to simplify the human aptitude to suf-
fer and feel pain down to the level of circuits, synapses, and
complex networks, but we should remain conscious and vigi-
lant of our need and desire to study and ultimately under-
stand human sapience while simultaneously finding ways to
aide and heal them. At the same time, we should not ignore
human complexities while pursuing our reductionist desire to
explain humanity in terms of biomechanical models.
As practitioners, neurosurgeons may be able to relieve
patient pain in ways that our clinical forefathers never dreamed
or imagined. But let us not become complacent and fall into the
deception that our work is complete. We must surely continue
our explorations of the body and brain. But if we are going to
fulfill what may, in the end, turn out to be the only meaningful
goal of existence—the Greek ideal of knowing oneself—let us
keep open the questions of psyche and soul and not entirely
succumb to the contemporary trend of scientific materialism
that would completely reduce humans to molecules and our
sentience to computer-like processes.
The Future
Neuroimaging has brought a brilliant new light to the com-
prehension of pain for the neurological understanding of psy-
cho-affective disorders. Although there is an abundance of liter-
ature on the subject of experimental acute pain, the question of
brain neuroimaging in the area of chronic pain has, to date,
been poorly reported. Nevertheless, while functional neu-
roimaging of patients has revolutionized medicine by providing
unique insights into some of the most common diseases affect-
ing humans, the seemingly simple question of headache and its
comprehension continues to remain a leading subject.
Neuroimaging investigations that have been focused on the
mapping of the so-called “pain matrix” (Fig. 17) by both clin-
ical and experimental studies show an unmistakable interac-
tion between the intensity of pain and emotions that are asso-
ciated with reflexes and behavior. Studies of brain imaging
with PET and fMRI provide insight into the nociceptive sys-
tem that carries pain via the ascending spinal pathways and
to the so-called “higher central structures.” The spinal path-
ways converge at the brainstem, thalamic nuclei, and sensori-
NEUROSURGERY
PAIN AND PSYCHO-AFFECTIVE DISORDERS
FIGURE 17. The pain network components. PPC, pos-
terior parietal cortex; S1/S2, primary and secondary
sensory cortex; SMA, supplementary motor area; ACC,
anterior cingulate cortex; PFC, prefrontal cortex; PAG,
periaqueductal gray.
motor cortex, but they also converge on the limbic circuit that
includes the amygdala, the posterior hypothalamus, the
insula, and the anterior cingulate cortex (ACC). PET studies
show an activation of the ACC by somatic and visceral pain
that has been interpreted as the neuronal basis of the emo-
tional response to pain. The activation of the insular cortex
appears in studies of nociceptive stimuli such as the injection
of ethanol, in tactile stimulation, and during cluster headache
(47) and atypical facial pain (24). Due to its anatomic connec-
tions, the insula seems to function as a relay station that sends
information to the limbic system along with control of the
autonomic response (72).
The thalamus has been fairly well established as the relay sta-
tion of acute pain. Animal experiments and functional imaging in
humans show the activation of the contralateral thalamus when
nociceptive pain is induced (indeed, the pain receptor location
plays an important role in the behavior of FANS and their with-
drawal). Moreover, it is known that the primary somatosensory
cortex has a clear somatotopic organization in response to painful
stimulation, and the representation of hand and foot in response
to the same stimuli appears in the contralateral insular region of
the secondary somatosensory cortex (11, 12).
Functional imaging has been able to demonstrate that a form of
spatial coding is preserved in the regions of afferent pathways,
such as the thalamus primary and secondary somatosensory and
the insula, but also in subcortical structures of the motor system,
such as the putamen red nucleus and cerebellum (10).
This anatomic-functional neuronal arrangement may be the
basis of pain transmission and processing, modulating the noci-
ceptive system with neuronal mechanisms that are associated
with anticipation, expectation, cognitive factors, and finally with
building the pain matrix.
In the literature, there are only a few studies on imaging, with
PET or fMRI, that address the subject of clinical pain. This is in
sharp contrast to the subject of experimental pain, which has a
relatively richer and more plentiful representation in the literature
(23, 81). This is doubtlessly because it is difficult to arrange
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BROGGI
homogenous group of patients with the same symptoms, the
same duration of disease, and the same age distribution to allow
for statistical significance that is noteworthy (13). With that said,
the differences in the literature on clinical versus experimental
pain should be noted. Quite a few recent studies on CNS meta-
bolic modifications have begun to appear on the subject of neu-
ropathic pain (46, 50), facial pain in trigeminal autonomic cepha-
lalgia (TAC) (3, 104), chronic back pain (28), fibromyalgia (110),
and on the complex regional pain syndrome (65).
Although this is encouraging, none of these studies have
provided reproducible pathognomonic findings of the disease
or even a pathophysiological basis for these syndromes.
The reaction to nociceptive pain is mediated by the brain
through a complex response that is not completely related to pain
stimuli. Pain is an unpleasant sensation often accompanied by an
emotional feeling, cognitive factors, and behavioral responses,
probably because pain can be so fundamentally life-threatening.
These qualities and these reactions to the feelings of pain seem
capable of prompting a significant impact on functional imaging.
These studies confirm what neurophysiologists have been pro-
posing for many years—that two ascending spinal pathways that
carry pain exist: the lateral and the medial spinal thalamic tract.
The lateral pain system consists of lemniscal projection to
the ventroposterior lateral nucleus of the thalamus and to the
primary and secondary somatosensory cortex, and it is
allegedly responsible for discriminative sensory pain transmis-
sion. The medial pain system includes the polysynaptic medial
spinal thalamic tract, the reticular formation of brainstem, the
amygdalae, the hypothalamus, and cingulated cortex. This last
system seems to be responsible for the process of the emotional
and affective components of the response to pain. Functional
imaging has revealed the neuronal circuit involved in the cog-
nitive and modulating aspect of pain. This neural mechanism
coupled with psychophysiological phenomena like placebo,
hypnosis, and biofeedback does have an effect on pain percep-
tion, probably by the modulation of the activity of the medial
pain system. This modulation will include an endogenous neu-
romodulator mechanism of pain inhibition and facilitation with
final pathways impinging on the spinal dorsal horn, where the
gate theories are thought to take place.
Imaging studies have shown that the ACC is involved in
pain perception and also in the dreamed pain experience (82)
as well as when one human observes another human experi-
encing pain (95). The placebo response to pain appears to be
mediated by the ACC (105) as well as by the response induced
by hypnosis (26).
PET studies in migraine patients show that rCBF values are
higher during acute attacks, particularly in the brainstem struc-
tures, in the dorsal pons, and in the ACC and the auditory asso-
ciation cortex (107). These increases in rCBF were observed to
persist after headache pain relief is achieved by drug consump-
tion, and these increases are not present when there are no
attacks. These results suggest that brainstem activation is not the
result of pain perception but rather is the primum movens of the
migraine or the headache itself. Its dysfunction results in a
decrease in the regulation of antinociceptive mechanisms and in
SHC916 | VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT
the extracerebral and intracerebral control of the vascular man-
ifestation of the headache. Another example of the media sys-
tem that is involved in pain control has been reported in stud-
ies with PET on headache patients who overuse medication.
Before withdrawal, the thalamus, orbitofrontal cortex, anterior
cingulate gyrus, insula, ventral part of the striatum, and right
inferior parietal cortex were found to be hypermetabolic,
whereas the vermis of the cerebellum was hypometabolic; after
the withdrawal of analgesics, all those structures, with the
exception of the orbitofrontal cortex, became normal. These
results are similar to the findings of withdrawal in drug addicts
and may explain why psycho-affective disorders that are usu-
ally correlated with chronic pain (39).
The imaging studies on TACs showed that cluster headache
and SUNCT have an activation effect on the posterior hypo-
thalamus (68), which prompted the use of DBS on this neuronal
volume to successfully treat these pain diseases. In those
patients, PET studies showed that DBS induces activation and
deactivation of different brain areas, although mainly in the
orbitofrontal cortex (Brodmann’s Area 25) (69, 70, 92). These
data argue against a nonspecific pain control by the hypothala-
mus, but they are supportive of the idea of a pain modulation
network. Recent neurophysiological studies have demonstrated
a functional neuronal reorganization in the cortex during
chronic pain diseases such as phantom pain, low back pain,
and chronic regional pain syndrome or causalgia. These data
were confirmed using single voxel MRI morphometry, an imag-
ing technique that allows for the study of gray matter. This sug-
gests that the adult brain may be able to modify the structures
that are involved in the perception of pain. A further question
that remains, however, is whether the pain circuitry is connected
and if it interferes with the modulation of the psycho-affective
trait, particularly in the dynamic process of chronic pain.
There seems to be little doubt, however, that there will be
studies that use the most advanced form of fMRI and PET in
chronic pain and in psycho-affective disorders that will bring
new light to this central element of the human experience—one
that exists from the skin’s receptors to the CNS and, somehow,
to the psyche.
CONCLUSIONS
Neuropathic pain and psycho-affective disorders share a
similar core of qualities and, in all likelihood, a common brain-
neuronal mechanism. Although both of these disorders con-
tinue to evade a clear objective cure, they can now be treated by
complex modalities that provide a fair to good level of symp-
tom control.
Because of these facts and these observations, it seems reason-
able to speak of pain and affective disorders as sharing a common
neurophysiological mechanism. The pain that is experienced by
depressed patients, therefore, seems to be no different from the
pain that is associated with a post-herpetic neuralgia or with the
painful dysesthesia that is associated with the cryptogenic sellar
region. Pain is a psycho-affective disorder that involves both
depressive and obsessive components. To the ancients, pain (the
www.neurosurgery-online.com

poinè of the Greeks or the poena of the Romans) occurred when
humans clashed with the will of the gods. From this historical
light, we are tempted to suppose that the psychoaffective disor-
ders we now see have clinical similarities to the pain experience
that may be related to the hubris of modern humans. Blessed by
an abundance of technology and science, modern humanity
seems to naively believe that we are now able to defeat the gods
of the ancients and the God of the monotheists and, maybe even
more naively, to control life, death, and the intervening suffering
that is central to the experience of life.
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Acknowledgments
This article was made possible through the discussions, contributions, and help of
my friends Roberto Cordella, Ph.D, Ivano Dones, M.D., Angelo Franzini, M.D., Allen
Fertziger, Ph.D., Paolo Ferroli, M.D., Carlo Marras, M.D., Doni Ratti, M.Sa., and
Giovanni Tringali, M.D., to whom I am deeply indebted and whom I sincerely thank.
COMMENTS
I t is in the nature of neurosurgery to bring us face to face with the
extremes of human existence. Manipulating the anatomy, surgically
intervening in limbic and hypothalamic motivational structures, allows
the functional neurosurgeon to physically grapple with man’s most inti-
mate apparatus, the structures that define the quality of our existence,
the prime mover. Broggi’s review takes us on a tour of functional neu-
rosurgery’s past and present efforts to address maladies of this system.
It is the story of searching. Unlike the field of movement disorders,
pain neurosurgery cannot boast consistent, dramatic results. Rather, we
have a long tradition, first of lesioning and now of neuromodulation,
accompanied by substantial conflicting data. In the end, it is clear that
some patients experience a diminution of their suffering. Practically,
therefore, the pain neurosurgeon must work from least invasive to more
invasive, searching for an option for each individual patient.
Early in the review, he characterizes the dilemma of limited objective
means to assess our outcomes. That is, at best we currently use blunt
tools such as the visual analog pain scale to quantify our patients, pain
and, hence, our success. Approaches of this kind lack the objectivity of
angiography. However, it is the particular role of the self and our eval-
uative apparatus that lies at this heart of this dilemma. Raw nocicep-
tion may be downregulated by 50% in two patients constituting crite-
ria for a successful treatment. One of these patients may continue to
obsess about the pain with which he or she lives with until he comes
to forget that his pain had previously been more severe. This patient
will report a failure of therapy. The second patient may be delighted
with this result and use the improvement to allow them to return to a
more productive lifestyle. Any “objective” assay that takes into account
the higher cognitive apparatus of value must incorporate this dimen-
sion of the patient’s belief. Nonetheless, attempts to quantify subjective
experience are vulnerable to even simple malingering.
Philosophically, I can only fault Dr. Broggi on what are ultimately
semantic points. First, he writes that he intends to “renew the interest in
timeless questions,” but I don’t believe interest in these questions
waned. I would agree, however, that psychoaffective surgery rubs our
noses in the mind-brain unity. Moreover, Dr. Broggi writes, “We in med-
icine, and not the philosophers, may be the ones responsible for shifting
the balance,” implying that physicians cannot be philosophers. Yet, the
present article is both a medical and philosophical treatise. Science or
empiricism, if our practice can be called that, is merely a school of phi-
losophy that has overshadowed its sisters. The author points out that
surgery on the affective system forces us to confront the mind-brain
unity. Philosophy is a rigorous methodology that arms us for that onto-
logical, existential, and ethical confrontation.
In the vein of this rigor, there are a number of other semantic issues.
Broggi writes that in addressing “questions of pain,” we “enter this
uniquely human metaphysical world.” Yet, the philosophy of mind
must acknowledge that the property of mind can or could be sub-
served by other physical apparati. The alternative is to believe that
only the human brain can subserve the mind, which strays dangerously
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BROGGI
close to pure materialism. Materialists hold that suffering is just
another series of synaptic neurochemical events. Pure materialism has
very little room for zen, very little room for a soul. So, I would not go
so far as to place emotional suffering in a unique human sphere. A vari-
ety of other schools of the philosophy of mind have arisen to cope
with these issues. For example, Functionalism holds that our mental
states are defined by their functional relationships with sensory input,
other mental states, and behavioral output. Put another way, suffering
can be better defined by its role as a motivational state, than by the neu-
rochemical events that happen to subserve that motivational state in
the human brain. Thus, philosophers have continued to grope for
means to explain how a material organ can subserve the functions of
psyche, identity, ethics, perception, and the soul. These efforts have
provided a variety of explanations that leave us middle ground
between materialism and raw Cartesian dualism.
Nicholas M. Boulis
Atlanta, Georgia
I n this treatise, Dr. Broggi attempts to bring together a decades-long
personal experience in the treatment of pain with knowledge of neu-
roanatomy and medical history in order to shed light on neurosurgery
for pain. While fundamentally a philosophical treatise on the origins of
pain and suffering, this article tries to make sense of the various neu-
rosurgical targets for pain and reasons why they may have succeeded
or failed based upon underlying neuroanatomical considerations. The
discussion of such a broad topic within the framework of a journal arti-
cle is bound to be uneven in its treatment of the subject matter.
Therefore, many of the procedures discussed receive only brief men-
tion. Moreover, this subject matter has been discussed in great detail in
many pain surgery texts. However, although the historical background
may have been discussed in the context of previous articles, Broggi
does provide a nice synopsis of current trends and developments in
pain neuromodulation and shows just how intricately connected
psycho-affective circuits and pain circuits really are.
Oren Sagher
Ann Arbor, Michigan
S ir Charles Sherrington, the most famous of English neurophysiolo-
gists, once said that “Pain is the psychic adjunct of an imperative pro-
tective reflex.” This concise and accurate observation not only defines
the acute response to a noxious stimulus, but also refers to the psycho-
logical consequences of a painful stimulus in terms of memory, learning,
and suffering. The “psychic adjunct” that Sherrington refers to recog-
nizes that a painful experience can be one of the most powerful and
compelling stimuli for behavioral change and the affective condition.
Sir Henry Head described two types of pain. The “fast,” or epicritic
pain, was well localized, sharp, short-lasting, and transmitted by the A
delta fibers. This epicritic pain allows the organism to react quickly to a
SHC920 | VOLUME 62 | NUMBER 6 | JUNE 2008 SUPPLEMENT
noxious stimulus and withdraw in a reflexive way. There is no affective
component associated with this response to a noxious stimulus. Head
also described a “slow,” or protopathic pain, which he felt represented
the slower, more poorly localized dull ache that follows the acute pain,
which is often longer lasting and has a more enduring affective compo-
nent. This type of pain affects the psyche of the organism, causes some
suffering, and teaches the organism through its connections with the
limbic system to avoid that stimulus if possible in the future.
There is no question that, as Dr. Broggi has pointed out, the neuro-
biological systems subserving primary pain pathways and psycho-
affective disorders share similar neuronal networks and connections.
The sensory input of all physical noxious stimuli into the nervous sys-
tem are similar, and the fast or epicritic response to such a stimulus is
programmed via thalamocortical striatothalamic circuits that are sub-
stantially sensorimotor. The sensory input also stimulates thalamocor-
tical striatothalamic circuits that have much more to do with memory,
learning, and limbic function. It is this component that imparts the
more conscious appreciation and perception of the painful experience.
When this cortical appreciation of the painful stimulus persists, we are
presented with a chronic pain that no longer needs a primary nocicep-
tive stimulus to maintain the “painful” state.
Cingulotomy has long been used for treating patients with unremit-
ting cancer pain or chronic pain of nonmalignant origin. In patients
with cancer pain, cingulotomy is generally successful at immediately
relieving pain in the majority of patients. Patients describe that they
can still appreciate a nociceptive stimulus, but that it doesn’t seem to
bother them. It is as though the affective component of the painful
response has been reduced. Frequently, after 9 to 12 months, if the
patient survives their cancer, the pain returns gradually to near base-
line levels. In most cases, patients succumb to their primary disease
before this occurs.
In patients with pain of non-malignant origin, cingulotomy has been
helpful in chronic low back pain, chronic abdominal pain, and a vari-
ety of other conditions. It is unclear if the beneficial effects are due to
a disruption of pain perception or if over the longer term, any endur-
ing effect is due to the amelioration of a depressive state that often
accompanies chronic pain. I favor this explanation as ablative surgery,
either peripheral or central, rarely cure painful states in the long term.
It is very clear that cingulotomy is very useful in the treatment of
severe, treatment refractory, chronic affective disorders, and obsessive
compulsive disorder. The fact that cingulotomy is beneficial in acute
pain, chronic pain, and the affective disorders implicates a common
pathway outlined by Broggi. Deep brain stimulation allows us to
explore targets that we know are involved in both the appreciation of
pain and its affective components. We are now on the threshold of a
better understanding of the complicated interaction between pain and
the psyche. It will be a very interesting and exciting decade.
G. Rees Cosgrove
Burlington, Massachusetts
www.neurosurgery-online.com