OEF/OIF Pain
Research Summit
Imaging
Dr. Cook presented
data discussing his parallel work in fibromyalgia (FM) and Gulf War
veterans (GVs) with chronic musculoskeletal pain (CMP).
Dr. Cook’s work
and the work of others suggest that FM pain may be maintained by central
nervous system mechanisms. These mechanisms may involve abnormal central
processing of sensory stimuli, abnormal central regulation of sensory
stimuli or a combination of augmented processing and diminished regulation.
It was proposed
that functional neuroimaging methods such as functional magnetic resonance
imaging (fMRI) can provide information regarding the extent and location
along the neruoaxis of central dysregulation, as well as, provide information
concerning what regions are involved in abnormal pain processing in
OEF/OIF veterans.
Dr. Cook presented
data showing augmented processing of both painful and non-painful stimuli
in GVs with CMP similar to that seen in FM. His data demonstrated pain-relevant
responses in the brain to warm stimuli that were not moderated by the
delivery of several painful stimuli in GVs with CMP compared with controls.
Controls showed less activity to warm stimuli that was further diminished
by the delivery of several painful stimuli. He further showed augmented
responses to mild, moderate and strong pain stimuli in GVs with CMP.
A dose response to graded pain stimuli was evident in healthy GVs, but
not GVs with CMP providing further evidence of augmented central processing
of pain.
Dr. Cook presented
preliminary data from his recent work in FM demonstrating augmented
brain responses to warm stimuli that were influenced by anticipation.
These results suggest greater anticipation of painful events for FM
patients and support one potential mechanism of chronic pain maintenance
in CMP. Healthy women showed top-down regulation of pain responses during
pain and distraction with increased activity in cingulo-frontal regions
and decreased activity in the anterior insular cortex. This response
was not evident in FM suggesting a failure to cognitively modulate pain.
Discussion focused
on the future of neuroimaging methods to study CMP, particularly as
it relates to OEF/OIF veterans. Many questions were posed as to the
meaning of a particular neural response and the specificity of neuroimaging
to provide neural maps of ‘pain’.
Proponents of functional
imaging methods as pathophysiological indices of pain pointed out the
potential to further understand brain mechanisms of pain in CMP and
the ability to test processing and regulatory aspects of pain that cannot
be obtained by measures that solely rely on self-report. Skeptics questioned
whether brain imaging provided anything unique beyond that of the self-report.
This was a good discussion.
There was general
consensus that brain imaging was not a surrogate for self-report and
that the subjective nature of pain required that pain always be measured
at the person level in addition to any “objective” correlate of
the experience. Additionally, brain imaging methods were recognized
as providing support for the subjective experience.
Discussion was also
focused on the potential of neuroimaging methods to track brain and
pain responses in treatment trials perhaps as a means to look at responders
and non-responders. Brain imaging methods may be useful to look for
the most reliable neural response for treatment and to look at the relationship
between neural responses to pan and CMP symptoms.
The second speaker,
Dr. Eva Widerström-Noga, gave an overview of the problem of SCI-related
pain and her new study using MR spectroscopy in individuals who have
suffered a spinal cord injury (SCI) and who experience chronic neuropathic
pain. Chronic pain is common following SCI and recent studies from the
US, Germany, Denmark and the Netherlands indicate that at least 2/3
of persons who have sustained a SCI will develop chronic pain. Furthermore,
most neuropathic pains are refractory to treatment and several studies
show that few of these pains completely resolve spontaneously or due
to treatment. SCI-related pain is superimposed upon the physical impairments
and disability caused by other consequences of SCI and one of the major
reasons for decreased quality of life after a SCI.
Because pain after
SCI is heterogeneous including both nociceptive and neuropathic pain
types, an individual often have several types of pain simultaneously.
This fact complicates the treatment since it is likely that several
pathophysiological and psychosocial mechanisms are responsible for causing
and maintaining a person’s pain. While basic research studies have
identified several possible pathophysiological pain generating mechanisms,
it is difficult in the clinical treatment situation to determine the
exact mechanism for as specific pain.
Although peripheral
mechanisms are involved in the generation of pain, central mechanisms
may play a larger role in SCI and other traumatic injuries and diseases
involving the central nervous system. For example, pain has been shown
to activate large areas of the brain, and a network consisting of both
cortical and subcortical structures has been suggested. For psychological
factors involved in the experience of pain (i.e., anticipation of pain,
attention, hypnotic reduction of pain, anxiety and placebo responses),
the prefrontal, anterior cingulate and insular cortices have been implicated.
In neuropathic pain conditions, increased activity has been found in
the somatosensory cortices I and II, prefrontal cortex, thalamus, anterior
cingulate cortex and insular cortex.
Magnetic Resonance
spectroscopy (MRS) is a non-invasive method to measure metabolites in
the human brain, which is based on that different chemicals vibrate
at different frequencies when stimulated by a magnet. MRS produces a
signature of the nature and amounts of chemicals that are present in
the brain. The stability of these signals is thought to be reflective
of long-term plasticity and may therefore be particularly useful in
longitudinal studies or clinical trials.
Dr. Widerström-Noga
and her colleagues have previously used MRS to study metabolic changes
in the thalamus related to neuropathic pain in persons with SCI and
chronic neuropathic pain. In this study they found that there are changes
in thalamic metabolites specific to neuropathic pain. In their new study
they focus on two metabolites: (1) N-acetyl aspartate, which
is a free aminoacid thought to be localized in neurons in the brain
and commonly considered a neuronal marker and an indicator of neuronal
dysfunction; and (2) Myo-inositol, which is an organic osmolyte, with
a major role in the volume and osmoregulation of astrocytes and is considered
a glial marker. In this new study, brain areas important for both the
sensory and affective processing of pain are examined. This research
aims to further our understanding of the role of metabolic processes
in the thalamus and anterior cingulate cortex and their relationships
with psychosocial factors and neuropathic pain in SCI.
In conclusion, chronic
pain associated with SCI is both heterogeneous and refractory. Multiple
pathophysiological and psychological mechanisms are responsible for
the origin and maintenance. With the goal of tailored mechanism-based
treatments, specific pain generating mechanisms need to be identified
in each person and treatment targeted to these.