Fibromiyalji Sendromunda “Nöro-geribildirim Tedavisi” Kitap Bölümümüz Amerika Birleşik Devletleri’nde Yayınlandı
Kronik ağrı (fibromiyalji sendromu) ile ilgili ABD yazarları ile birlikte yazdığımız “Clinical Neurotherapy” kitabı yayınlandı. Bu kitapta, beyin dalgalarının çeşitli hastalıklarda tedavi programları doğrultusunda değiştirilebilmesini konu alan Nöro-feedback (Nöro-geribildirim) konusu tüm detayları ile incelendi. Bu kitapta, Prof. Dr. Erbil Dursun ve Prof. Dr. Nigar Dursun ise nöro-geribildirim tedavisinin kronik ağrıda (fibromiyalji sendromu) kullanımını yazdı. Aşağıda bu kitapta yazılmış bölümü sizlere sunuyoruz.
Erbil Dursun and Nigar Dursun
CHAPTER TEN: Treating Chronic Pain Disorders
Chronic pain is a common problem and expensive to treat. The success
rate of all the available treatments for this condition is limited, because it
rarely responds to the therapeutic measures that are successful in treating
acute pain.1 For the majority of patients, the currently used treatments can
not eliminate pain adequately.2 Besides, most of the pharmacological treatments
used for chronic pain often have adverse effects, especially dependence
on pain medications. For these reasons, as the mechanisms of pain
become better understood, new interventions that may affect pain at the
cortical level are being developed.3–5
For many years, biofeedback and relaxation therapies have been used
in addition to medical approaches to treat acute and chronic pain syndromes.
The term biofeedback covers a group of therapeutic procedures
that use electronic or electromechanical instruments to properly measure,
process and feed back to patients in the form of auditory and/or visual
signals using information about their normal and/or abnormal neuromuscular
and autonomic activity.6 Biofeedback is used to help patients
develop a greater awareness of and an increase in voluntary control over
their physiological processes, which are otherwise involuntary and unfelt.
In psychiatry, biofeedback has been used in a wide range of clinical conditions,
such as motor weakness,7,8 balance and gait disturbances,9,10 spasticity,
11 neurogenic bladder12 and bowel dysfunction,13,14 and speech15 and
swallowing problems.16 It has also been used in the management of various
acute and chronic painful conditions, such as temporomandibular joint
dysfunction,17 headaches,18 lower back pain19 and patellofemoral pain
syndrome.20,21 In addition, biofeedback treatment is also suggested to be
helpful in the management of fibromyalgia syndrome (FMS).22
Electroencephalographic (EEG) biofeedback is an operant conditioning
procedure that can alter the amplitude, frequency or coherence of the
neurophysiological dynamics of the brain. Therapeutic application of EEG
biofeedback is often referred to as neurofeedback, and it has various clinical
applications, such as migraine,23,24 epilepsy,25 attention deficit hyperactivity
disorder (ADHD),26–28 alcohol abuse,29 sleep disorders30 and chronic
fatigue.31 Sensorimotor rhythm (SMR) training is a commonly applied
neurofeedback protocol that is normally associated with a quiet body
and an active mind, and appears to facilitate thalamic inhibitory mechanisms.
32 On the other hand, studies in epileptic patients with SMR training
showed significantly increased EEG spindle densities during sleep and
prolonged sleep episodes, and a related decrease in state conversions.33,34
In this way, SMR treatment suppresses some of the pathological consequences
of epilepsy and potentially reduces vulnerability to a convulsion.
As described by the International Association for the Study of Pain
(IASP), pain is an unpleasant sensory and emotional experience associated
with actual or potential tissue damage, or is described in terms of such damage.
According to IASP, pain is unquestionably a sensation in a part or parts
of the body, but it is also always unpleasant, and therefore also an emotional
experience. The IASP website continues: “Many people report pain in the
absence of tissue damage or any likely pathophysiological cause; usually this
happens for psychological reasons. There is usually no way to distinguish
their experience from that due to tissue damage if we take the subjective
report. If they regard their experience as pain, and if they report it in the
same ways as pain caused by tissue damage, it should be accepted as pain.”
If pain is considered only as a symptom associated with physical damage,
and is understood as a simple response to physical damage, then nociception
must be transmitted via a simple channel directly to a “pain perception area”
in the brain. If we consider it like this, pain must be thought of as being
related only to physical damage that occurs in the periphery. In this regard
the brain is seen as a passive perceiver of sensory information. Melzak and
Wall35 integrated the physiological and psychological aspects of pain according
to the gate control theory of pain. This theory declares that the dorsal
horn of the spinal cord acts like a gate, regulating the flow of impulses from
the peripheral nerve fibers to the brain. The gate is influenced by peripheral
fiber activity and by descending influences from the central nervous system.
Thus, this system explains how pain stimuli are adjusted in the spinal
cord before moving to the brain. At present, as we better understand the
mechanisms of pain in relation to the brain itself, our perceptions regarding
pain are changing from the periphery and spinal cord to the brain itself.
Supraspinal mechanisms are increasingly accepted as playing a major role in
the representation and modulation of pain.36
Nociceptive stimuli are influenced on many levels in the brain, such as
the cortex, insula, anterior cingulate and thalamus. Hyperalgesia is related
to changes at the site of injury as well as to hyperexcitability in the central
nervous system, which results in long-term changes to the nervous
system, known as plasticity.37 This hyperexcitability is also known as central
sensitization and leads to increased activity at higher brain centers. It
is likely perceived as more intense and prolonged pain.38 A number of
pathophysiological processes are suggested as responsible for the diffuse
pain of FMS, including central pain processing systems, the hypothalamopituitary–
adrenal axis and the autonomic nervous system, in which central
pain syndromes are the most productive area of research.39 There is
increased tenderness to pressure in FMS, and augmentation of pain caused
by central mechanisms. Augmentation of pain, such as windup,40 or weakened
effects of descending antinociceptive pathways, are examples of
central mechanisms.41 FMS patients have not only sensitivity to pressure
stimuli but also decreased nociceptive thresholds with regard to heat, cold,
electrical stimuli and even sound. The review by Williams and Clauw39
focuses on their current understanding of FMS as a prototypical central
pain syndrome. They stress that the terms central augmentation or central
pain threshold are different from central sensitization, and because the
tenderness or hyperalgesia occurs far away from the area of pain, central
augmentation or central pain are likely to be more suitable terms for what
is seen in FMS.
Deactivation of inhibitory processes in the central nervous system
arouses interest.38,42–44 Because the caudate nucleus and thalamus are both
involved in signaling the occurrence of noxious events, low regional cerebral
blood flow, which indicates decreased functional activity, is a marker
for impaired inhibition of nociceptive transmission by these brain structures.
38 In chronic pain states, thalamic blood flow is reduced, whereas
acute pain increases thalamic blood flow.45,46 In a controlled study47
the total Fibromyalgia Impact Questionnaire (FIQ) score in patients
was positively correlated with blood flow in the parietal lobe, including
the postcentral cortex. This correlation was seen in the areas of significant
hyperfusion. Also the total FIQ score was negatively correlated with
blood flow in a left anterior temporal cluster, one of the areas of significant
hypoperfusion. The authors concluded that brain perfusion abnormalities
in patients with FMS are correlated with the clinical severity of
the disease. Mountz et al.46 measured resting-state regional cerebral blood
flow in the hemithalami and left and right heads of the caudate nucleus in
10 untreated women with FMS and seven normal control women using
single-photon emission CT (SPECT). They also evaluated pain thresholds
at tender and control points. Regional cerebral blood flow in the left and
right hemithalami and the left and right heads of the caudate nucleus was
found to be significantly lower in women with FMS, as were lower pain
threshold levels. The authors concluded that abnormal pain perception in
women with FMS might result from a functional abnormality within the
central nervous system. Kwiatek et al.45 measured regional cerebral blood
flow using improved SPECT and advanced complementary analytic techniques
in resting female FMS patients and in age-, gender-, and education-
matched healthy controls. They confirmed that thalamic regional
cerebral blood flow is reduced in FMS, but to a statistically significant
extent only on the right. Low thalamic regional cerebral blood flow has
been observed not only in patients with FMS, but also in patients with
other chronic pain disorders, such as chronic neuropathic pain, metastatic
cancer and mononeuropathy.38 It may be that low thalamic regional cerebral
blood flow, which indicates decreased functional activity, is a marker
for impaired inhibition of nociceptive transmission by brain structures
such as the caudate nucleus and thalamus.
Several studies suggest that P300 indicates the activation of inhibitory
processes in the central nervous system, and a reduced P300 amplitude
may demonstrate a deficit in these inhibitory mechanisms.48 It was
reported that P300 amplitudes were reduced in clinical conditions such as
alcoholism, ADHD and Alzheimer’s disease.49–51 Hada et al.52 declared that
the lower P3a amplitude and weaker sources in alcoholics suggests disorganized
inefficient brain functioning, and this global electrophysiological
pattern suggests cortical disinhibition perhaps reflecting underlying central
nervous system hyperexcitability in alcoholics.52 Reduced P300 amplitudes
are seen in patients with FMS, and sertraline was shown to increase
the amplitude of P300 within 8 weeks.53,54 SMR training increases P300
amplitudes, which supports the observation that SMR training facilitates
thalamocortical inhibitory mechanisms.55
These findings have important implications regarding treatment, because
the pain of tissue or nerve damage can be attacked at the site of the injury
where it is initiated, as well as at central nervous system sites where it is maintained.
38 Interventions that reprogram or interrupt central sensitization could
provide significant relief for some individuals with chronic pain, and the
understanding that pain experience is modulated at many levels of the central
nervous system opens the door to interventions that might affect pain at
the cortical level, including treatments such as neurofeedback.56 On the other
hand, with regard to P300, we can assume that neurofeedback treatment may
play an inhibitory role on the central nervous system, and this may alter central
augmentation in FMS. In this way, we can hypothesize that neurofeedback
treatment will be effective in alleviating the symptoms and signs of FMS.
Ibric and Dragomirescu57 discusses 147 chronic pain patients, 10
of whom were presented as case studies. All of the 147 patients had little
resolution of pain with other treatment modalities. The 10 case study
patients had diagnoses including reflex sympathetic dystrophy, headache,
neuropathy, myofascial pain, left inguinal pain, chronic lower back and leg
pain, and FMS. In all cases the neurofeedback treatment involved SMR
enhancement as well as theta and high beta discouragement. The patients
had positive improvements after the neurofeedback treatment. The authors
noted that the results of neurofeedback were highly dependent on the
number of sessions: when sessions numbered 19 or fewer, the rate of success
was very reduced, but when the patients had completed more than 19
sessions of neurofeedback training, the success rate was evident.
In our rater-blinded controlled study5 involving 40 patients with FMS
randomized into either a neurofeedback (enhanced SMR activity and
decreased theta activity) or a control (escitalopram treatment) group, each
neurofeedback session was 30 minutes long and the patients had five sessions
per week. Each patient was trained at the same time of day for 4
weeks. The symptoms of FMS and the clinical grading scales were noted
at baseline, and at the second, fourth, eighth, 16th and 24th weeks for both
groups. The Visual Analogue Scale (VAS) for pain, VAS for fatigue, FIQ
and Short Form-36 (SF-36), Hamilton Depression Scale (HDS), Beck
Depression Scale (BDS), Hamilton Anxiety Scale (HAS) and Beck Anxiety
Scale (BAS) were applied. Also, the mean amplitudes of alpha, beta 1, beta
2, theta, delta, SMR and theta/SMR ratios were recorded at baseline and
at the second, fourth, eighth, 16th and 24th weeks in the neurofeedback
group.VAS pain and VAS fatigue scores were significantly decreased by the
end of the study period in the two groups. However, the values of the
neurofeedback group were significantly lower than in the control group
at all posttreatment assessments, even at the end of the 24th week. These
findings emphasize the positive effects of neurofeedback on pain and
fatigue, with the reorganization of the brain structures perhaps owing to
facilitation of the thalamocortical inhibitory mechanisms.
Besides pain, patients with FMS have many other diagnostic symptoms,
such as fatigue, sleep difficulties, a swollen feeling in tissues, paresthesias,
cognitive dysfunction, dizziness, increased tenderness in multiple points,
morning stiffness, psychological disorders, abdominal pain, dysmenorrhea,
irritable bowel syndrome, headaches and restless legs syndrome. There is evidence
for central sensitization in these conditions.58 A neurogenic form has
also developed, suggesting that functional dysregulation of central pain pathways
could account for many of the clinical manifestations of FMS.45 The frequent
joining of chronic pain with several other chronic disabilities may not
be coincidental. A meta-analysis shows that the brain network for acute pain
perception in normal subjects is at least partially distinct from that seen in
chronic clinical pain conditions, and that chronic pain engages brain regions
critical for cognitive/emotional assessments, implying that this component
of pain may be a distinguishing feature between chronic and acute pain.36
There are brain regions that reduce their activity during task performance,
and these regions are the component members of the default-mode network.
Raichle et al.59 used quantitative metabolic and circulatory measurements
from positron-emission tomography to obtain the oxygen extraction fraction
regionally throughout the brain. Areas of activation were prominent by their
absence, and increases indicated deactivations. Baliki et al.60 proposed that
long-term pain alters the functional connectivity of cortical regions known
to be active at rest. They demonstrated that chronic pain has a widespread
impact on overall brain function, where the default-mode network shown
by functional magnetic resonance imaging is imbalanced and disrupted, and
disorders of the default-mode network may account for the development of
accompanying cognitive and behavioral impairments. Therefore, neurofeedback’s
effect in positively altering the brain functions may be founded on its
supporting effect in the correction of this cortical disruption.
As neurofeedback improves attention deficits, Caro and Winter61 reasoned
that FMS patients with cognitive and attention complaints might
benefit from an EEG-based modality. In their experience many FMS
symptoms correlate with one another. Because of this, they speculated
that if neurofeedback positively improved cognitive symptoms in FMS, it
might also improve somatic complaints. They included 15 FMS patients
with attention problems who completed 40 or more neurofeedback sessions
where the SMR protocol was used, which augmented 12–15 Hz
brain waves while simultaneously inhibiting 4–7 Hz brain waves (theta)
and 22–30 Hz brain waves (high beta). Sixty-three FMS patients who
received standard medical treatment but who did not receive EEG biofeedback
were included as controls. The neurofeedback group showed
significant improvements in visual attention, tenderness, pain and fatigue.
Albeit not statistically significant, there was also a trend toward improvement
in psychological distress and morning stiffness.
In an uncontrolled clinical trial, Mueller et al.62 prospectively followed
30 FMS patients through a brainwave-based intervention known as EEGdriven
stimulation. Besides this, patients had also other treatments, including
massage therapy, physical therapy and surface electromyographic neuromuscular
retraining. Before and after treatment and during an extended followup,
comparison of the number of positive tender points and pain thresholds,
psychological and physical functioning indices, and specific FMS symptom
ratings revealed statistically significant improvements. In our study,5 posttreatment
assessments revealed that neurofeedback and control treatments
caused significant improvements in depressive symptoms and anxiety; i.e.,
all the depression and anxiety scores (HDS, BDS, HAS and BAS) showed
significant improvements in both the neurofeedback and the SF control
groups, but the neurofeedback group displayed greater benefits than controls.
In addition, FIQ and SF-36 revealed significant improvements in both
of the groups, but the values of the neurofeedback group were significantly
better than those of the escitalopram treatment group during the whole
study period. These findings underline the positive effects of the neurofeedback
treatment on psychosocial aspects, quality of life and physical functioning,
in addition to other symptomatology of FMS. On the other hand,
the therapeutic efficacy of neurofeedback was found to begin in the second
week and reached its maximum effect in the fourth week, whereas the
improvements in escitalopram treatment were also detected to begin in the
second week but reached its maximum effect at the eighth week. This early
effect of neurofeedback may be related to a faster brain plasticity process and
certainly can be considered one of the advantages of this treatment.
Pain may be associated with relatively lower amplitudes of slower wave
(delta, theta and alpha) activity and relatively higher amplitudes of faster
wave (beta) activity.56 Morphine treatment alters brain waves in the lowfrequency
range (2–4 Hz) during the first 300 ms after stimulus, whereas
active brain waves remain unchanged after placebo treatment.63 The results
show significant slowing of the EEG in spinal cord-injured patients with
neuropathic pain, consistent with the presence of thalamocortical dysrhythmia.
64 Intense painful stimulation causes an increase in beta wave
activity and tends to reduce mostly alpha (slower) wave activity.56 Mueller
et al.62 obtained statistically significant reductions in delta, theta and alpha
waves after treatment. The relative predominance of low-frequency (delta,
theta and low alpha) activity detected at the beginning of treatment had
normalized by the end of treatment. In our study,5 no statistically significant
changes were noted regarding mean amplitudes of EEG rhythms.
However, the theta/SMR ratio showed a significant decrease by the fourth
week compared to baseline in the neurofeedback group. The detected
decrease in theta/SMR ratio is important and may show a concrete finding
concerning neurofeedback treatment. Thus, SMR neurofeedback
treatment may have a facilitator effect on thalamic inhibitory mechanisms
by arranging brain activity via increasing the slower waves and decreasing
the faster waves of the brain. Further well-organized controlled studies
with higher patient numbers are needed to verify this finding.
Pain is regulated by interactions between ascending and descending
pathways, and brain mechanisms are increasingly being accepted as having
a major role in the modulation of pain. Understanding these mechanisms
is crucial if fully effective treatments for clinical pain conditions are to be
The etiologic factors of chronic pain syndromes and the relationship
between chronic pain and central nervous system mechanisms need to
be clarified in future investigations. Because the EEG is an important
physiological tool, studies that use more quantitative EEG evaluations
with respect to pain would be very helpful. On the other hand, it is obvious
that scientific data are insufficient for neurofeedback interventions
regarding pain modulation. Many well-designed controlled prospective
studies with larger patient populations must be carried out in order to be
certain about the role of neurofeedback interventions on pain management
and its therapeutic mechanisms.
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