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Pain is a subjective
experience with a definite physical basis. The physical
indices associated with pain may not correlate well
with the subjective experience, such as measurable
degenerative changes in the lumbar spine and self-reported
intensity of low back pain. Other physical indices,
such as the gating mechanism in the spine that modulates
the degree of pain ascending to the brain, are well
studied but not objectively measurable in any routine
clinical test. Newer neuroimaging methods may finally
bridge the gap between subjective experience and objective
findings. This article illustrates some of these newer
methods and the possibilities for objective measures
of pain on the horizon.
Computerized tomography (CT) is essentially a three-dimensional
x-ray. The technique can readily identify bone fractures,
bleeding in tissues, and gross abnormalities in bodily
organs and structures. CT scanners are almost universally
available in health care settings and relatively inexpensive.
CT is highly sensitive to movement artifacts or the
presence of metals that can displace electrons and
distort the image. Magnetic resonance imagery (MRI)
requires a shielded location for a massive electromagnet,
is common but not universally available, and more expensive.
As the magnet turns on (very briefly), elements such
as the hydrogen in water rapidly align themselves in
the magnetic field, and heavier elements such as the
calcium in bone do not move as rapidly. Sophisticated
software can differentiate tissues and structure densities
with greater precision and definition than in CT. The
resulting reconstructed image can often reproduce bodily
structures with uncanny clarity. Images are weighted
in different analyses to create contrasts designed
to better identify common disease patterns and medical
conditions. The CT and MRI are essentially structural
methods, which identify physical abnormalities in tissues
and structures.
Another set of neuroimaging procedures are often termed
functional, that is, they measure active functional
activity within the brain or other bodily organs. One
of the more common techniques is the electromyogram
and nerve conduction velocity (EMG/NCV) test. Often
done as a combined test, the former assesses the responsiveness
of muscles to nerve stimulation. The latter assesses
the integrative integrity of the major peripheral nerve
pathways. The test is typically used to confirm conditions
such as carpal tunnel syndrome or radiculopathy caused
by compression of a nerve root in the neck or back.
Such a test has a better correlation with subjective
pain than would structural imaging, but that relationship
is still not perfect. The most common functional imaging
of the brain is the electroencephalogram (EEG). Systematically
placed surface electrodes measure the nature and intensity
of brain activity. It is sensitive to many seizure
conditions, gross abnormalities in consciousness, and
can identify some components of migraine. The technique
lacks sensitivity.
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| “Newer
neuroimaging methods may finally bridge the gap between
subjective experience and objective findings." |
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Biofeedback is not a neuroimaging technique per
se, but can assess the nature and intensity of physiological
aspects of physical functioning impacted by pain
conditions. Surface measures of skin conductance,
muscle tension, peripheral skin temperature, heart
rate, respiration rate and pattern, quantitative
EEG, and other measures can identify functional changes
relative to normal in persons with localized injury
or the generalized effects of pain through the autonomic
nervous system. The limitations of biofeedback are
lack of a universal standardized assessment procedure,
the susceptibility of measures to some medications,
caffeine and other substances, and variability in
how the methods are used. Measures may quantify and
substantiate subjective complaints. Biofeedback is
best used as a relative quantitative measure of an
individual’s response to pain treatment.
Newer and exciting neuroimaging techniques are often
blends of the structural and functional approaches,
but are usually limited in availability and require
highly specialized equipment, analysis software and
trained professionals to interpret the results. The
methods are very expensive and often denied by insurers.
Thus, the Official Disability Guidelines consider
these methods as potentially useful but not recommended
because the scientific body of evidence is still
insufficient. Cousins (2007) offers a succinct description
of the mechanisms involved in the pain response.
There are a variety of neural and chemical responses
at the location of a physical injury. In the context
of persistent pain, nerves can become sensitized
and over time adapt their function to the existing
trauma. In the presence of persistent pain, modulating
neurons at the level of the spinal cord can “wind
up” in response to a chronic pain signal, thus
amplifying peripheral signals not processed as “painful” prior
to an injury, such as touch or temperature change.
Through a shift in the balance of neurochemical activity,
loss of inhibitory control, and brain plasticity,
changes can also take place at the brain level that
make pain chronic and enduring, regardless of the
nature and extent of the original injury. Psychological
factors, genetics, and other physical characteristics
have a modulating effect on these neurological processes.
The chronic stress on the nervous system can also
lead to cell death, tissue shrinkage, and other enduring
structural changes that make pain far more difficult
to regulate. Woolf and Salter (2000) provide an even
richer and comprehensible description of the neural
changes at all levels of the nervous system in response
to persistent pain.
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| “Biofeedback
is not a neuroimaging technique per se, but can assess
the nature and intensity of physiological aspects of
physical functioning impacted by pain conditions.” |
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Pain is the most
dynamic of the human senses (Watkins and Maier, 2003).
There is no scientific doubt that pain experience is
physical and genuine. Its complexity is only beginning
to be appreciated. Pain is “in one’s head” only
because it is experienced in the brain. Treating pain
effectively and as early as possible in the course
of an injury is paramount to minimize these neural
changes. Appropriate pain treatment at any time may
attenuate negative experience and utilize the same
plasticity principles to shift pain modulation in a
positive direction. Neuroimaging can be useful to capture
these functional processes and subtle but important
structural brain changes.
Borrowing a simple analog model of the brain from Siegel
(2007), make a fist with the right hand (works with
the left but from the opposite point of view) and tuck
the thumb under the curled fingers. This is a lateral
view of the brain from the left side. The model needs
an extra thumb on the outside for the right temporal
lobe to be a more complete brain model. The curled
fingers represent the frontal lobes (executive functions),
the thumb the temporal lobe (sequential or contextual
processing and memory), the top knuckles the central
sulcus (fold) separating the frontal lobe before it
from the parietal lobe (integrated sensory processing)
behind it. The occipital lobes (visual processing)
would be represented by the base of the back of the
hand before the wrist. Assuming the right hand to model
the brain from the left hemisphere, an important structure
for all sensory processing is the cingulated gyrus
(a raised section of brain tissue). This is central
to the brain and wraps itself under the middle and
ring fingers and underside of palm. The cingulate is
activated when new sensory information comes in and
serves as a wake up to various areas of the brain to
process the information and to ready the brain for
action. Sticking the left index finger into the center
of the palm, the model now includes: 1) the top of
the finger as the diencephalon (thalamus, hypothalamus,
and pituitary which relay and modulate all sensory
input and direct hormones, “drives,” and
other internal functions, pain included), 2) the midbrain
(between 2nd and 3rd knuckles—knuckle one joins
the finger to the hand), which contains the brain’s
primary chemical factories and the center of which
includes the periaqueductal gray (essential area for
pain modulation), 3) the pons (between knuckles one
and two), which coordinates and regulates movement
and sensation with multiple connections to the cerebellum
(heel of hand), and 4) the medulla (left knuckle one),
which regulates all the basic functions of the body
including control over the intensity of the body’s
stress response. This simple brain model can provide
relative reference points for regions of the brain
as they are discussed.
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| “There
is no scientific doubt that pain experience is physical
and genuine. Its complexity is only beginning to be appreciated.
Pain is “in one’s head” only because
it is experienced in the brain.” |
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Traditional MRI
can identify structural brain changes attributed to
chronic pain, but the technology must use high-speed
resolution techniques and focus on regional volumes
instead of the usual clinical inspection of image slices.
May (2008) reviewed two methods applied to brain changes
associated with chronic back pain, migraine and tension
headache, fibromyalgia, and irritable bowel syndrome.
These methods are voxel-based morphometry (VBM) and
diffuse tensor imaging (DTI). More detailed general
descriptions of these and other imaging techniques
can be found at en.wikipedia.org. VBM focuses on tissue
volume in selected brain areas of interest and DTI
creates three-dimensional gradients based on tissue
volume. Gray matter tissue loss in multiple chronic
pain conditions has been found in the cingulate gyrus,
orbital frontal cortex (knuckle three to finger tip
of middle and ring fingers in the hand model above),
and insula (inner side of bent thumb closer to joint
One common combined functional-structural
method is the functional MRI (fMRI).
In addition to the structural and spatial
layout of structures on a MRI, fMRI
uses blood flow dynamics and rapid
sequential images to create a temporal
dimension that serves as an index of
functional processes. Orme-Johnson
and colleagues (2006) demonstrated
the effect of meditation on brain function
using fMRI. Healthy adults (average
age in mid-50s) were subjected to conditions
of the left hand being placed in warm
water (43° C, 109° F) as a
standard reference and the right hand
placed in hot water (51° C, 124°
F). Subjects who were experienced meditators
were able to have a significantly lower
pain response during the hot water
experience than those who were not
meditators. This was measured in several
areas known to respond to such pain.
The thalamus, which serves as the brain’s
primary sensory relay station, was
the most significant, with meditators
having much less activation than nonmeditators.
Nonmeditators were then taught a meditation
technique and practiced it for 5 months.
Activation in the long-term meditators
did not change compared to the first
time of measurement. New meditators
had reduced activation (better pain
modulation) at the follow up for the
thalamus and the prefrontal cortex
(2nd knuckles of curled right hand).
There was also a trend in the small
sample for reduced activation of the
anterior cingulate gyrus (underside
of index and ring fingers), which takes
sensory information from the thalamus
and activates the attentional aspect
of the frontal lobes.
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| “Gray
matter tissue loss in multiple chronic pain conditions
has been found…” |
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Baliki and associates
(2008) used fMRI to study information processing in
a small group of healthy adults and those with chronic
low back pain. They were particularly interested in
brain areas associated with the default-mode network
(DMN). The DMN paradigm involves brain areas that are
activated or deactivated during particular tasks. Because
the investigators were using a visual attention task,
subjects were expected to deactivate: 1) the medial
pre-frontal cortex (adjacent middle and ring fingers
in the model), which is associated with behavioral
and emotional calmness, 2) the posterior cingulate
(mid-palm back from center), which would rest processing
of sensations from the body, and 3) lateral parietal
cortex (off-center portions of back of hand), which
also would be associated with processing bodily sensations.
This deactivation allocates more attention to areas
involved in the target task, such as visual processing
and judgment of line orientation. The visual attention
task involved moving a finger joystick to continuously
match a changing line image. Persons with chronic back
pain performed the task as well as healthy controls,
but areas expected to deactivate did not. Results suggested
that chronic pain forces the brain to continuously
process pain sensations and prevent normal resting
activation.
Geha et al. (2008) used fMRI to study the effects of
light touch, which is experienced as painful in patients
with post-herpetic neuralgia. The virus-injured nerves
in such persons create constant burning and other noxious
sensations. Through mechanisms of sensitization, any
touch, even clothing for some people, can be extremely
painful. The task involved being touched with a light
brush in the affected pain area. The investigators
were able to determine time-sequenced activation of
the multiple areas in brain stem and cortex that would
process sensory pain information. Touch activated pain
was objectively worse than any spontaneous pain. Treatment
with lidocaine over two weeks seemed to help some individuals,
but overall treatment effects were not significant
based on aggregate fMRI data.
Using fMRI, Wrigley and colleagues (2008) were able
to document brain reorganization and areas associated
with neuropathic pain in persons with complete thoracic
spinal cord injuries (SCI). Reorganization of somatosensory
cortex (area on back of hand behind knuckles in the
brain model) has been well-studied in persons with
amputation, phantom pain, and stroke, but this study
did the same for persons with SCI. Neuropathic pain
was associated with zones of partial preservation of
sensory function.
Wiech and associates (2008) utilized fMRI to demonstrate
that decreased perceived pain while contemplating religious
art was associated with reduced activation in the right
ventrolateral prefrontal cortex (underside of right
pinkie), which is a brain area associated with emotional
regulation. Brown et al. (2008) utilized EEG and fMRI
to demonstrate that prior emotional distress ratings
in response to a painful stimulus (variable intensity
laser shot to forearm) affected subsequent brain activation
of the painful stimulus. Activation of the anterior
insula was associated with greater pain anticipation.
The hippocampus (inner thumb joint at knuckle two)
is a key area for memory encoding and reconstruction
and located just below the insula.
Positron-emission tomography (PET) is a technique that
involves injection of a radio-tagged sugar into the
blood stream. A task is performed and the PET scan
measures areas of brain activation. Kuehn (2005) summarized
multiple studies that have examined actual brain changes
in fMRI and PET that measured opiate-mediated response
in prefrontal cortex, anterior cingulate and insula
among other areas by use of placebo or manipulated
expectations prior to pain stimulus. In research underway,
Stanford University pain physician, Sean Mackey, and
colleagues are studying the effects of real-time fMRI
feedback and patient’s ability to regulate pain
experience.
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| “Persons
with chronic back pain performed the task as well as
healthy controls, but areas expected to deactivate
did not. Results suggested that chronic pain forces
the brain to continuously process pain sensations and
prevent normal resting activation.” |
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Although
not a standard of practice, functional MRI and several
other novel structural and functional neuroimaging
techniques are on the horizon for clinical application
that can objectify pain experience. Most scientific
studies to date have utilized small samples, did not
involve randomized controlled trials, and focused on
applying specific models to evoke pain experience.
However, the seminal research is consistently supporting
known functional brain areas involved in the processing
of pain sensation. The medical-legal realm must still
rely on subjective pain reports and consistency with
known pathology and behavioral manifestation. However,
if pain is a significant contested fact, fMRI at a
university-based facility studying pain might provide
an option for a qualified or independent medical evaluation.
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| “Although
not a standard of practice, functional MRI and several
other novel structural and functional neuroimaging techniques
are on the horizon for clinical application that can
objectify pain experience.” |
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Michael Gilewski, PhD,
ABPP (Rp, Cl)
Dept of Physical Medicine
and Rehabilitation (Neuropsychology)
Loma Linda University Health Care
11406 Loma Linda Drive, Suite 105
Loma Linda, CA 92354-3711
Tel: (909) 558-6220
Fax: (909) 558-6278
Email: mgilewski@llu.edu
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