BMC Musculoskeletal Disorders: Chronic Non-Specific Low Back Pain - Sub-Groups or A Single Mechanism?

BMC Musculoskeletal Disorders BioMed Central
Debate Open Access

Chronic non-specific low back pain – sub-groups or a single
mechanism?
Benedict Martin Wand*1 and Neil Edward O'Connell2
Address: 1School of Health Sciences, University of Notre Dame, Australia, 19 Mouat St, Fremantle WA 6959, Australia and 2Centre for Research in
Rehabilitation, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH, UK
Email: Benedict Martin Wand* - [email protected]; Neil Edward O'Connell - [email protected]
* Corresponding author
Published: 25 January 2008 Received: 31 January 2007

Accepted: 25 January 2008
BMC Musculoskeletal Disorders 2008, 9:11 doi:10.1186/1471-2474-9-11
This article is available from: http://www.biomedcentral.com/1471-2474/9/11
© 2008 Wand and O'Connell; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Low back pain is a substantial health problem and has subsequently attracted a
considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions
for chronic non-specific low back pain indicate limited effectiveness for most commonly applied
interventions and approaches.
Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of
effectiveness is at odds with their clinical experience of managing patients with back pain. A
common explanation for this discrepancy is the perceived heterogeneity of patients with chronic
non-specific low back pain. It is felt that the effects of treatment may be diluted by the application
of a single intervention to a complex, heterogeneous group with diverse treatment needs. This
argument presupposes that current treatment is effective when applied to the correct patient.
An alternative perspective is that the clinical trials are correct and current treatments have limited
efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important
that the sub-grouping paradigm is closely examined. This paper argues that there are numerous
problems with the sub-grouping approach and that it may not be an important reason for the
disappointing results of clinical trials. We propose instead that current treatment may be ineffective
because it has been misdirected. Recent evidence that demonstrates changes within the brain in
chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of
cortical reorganisation and degeneration. This perspective offers interesting insights into the
chronic low back pain experience and suggests alternative models of intervention.
Summary: The disappointing results of clinical research are commonly explained by the failure of
researchers to adequately attend to sub-grouping of the chronic non-specific low back pain
population. Alternatively, current approaches may be ineffective and clinicians and researchers may
need to radically rethink the nature of the problem and how it should best be managed.
Background for considerable healthcare and socioeconomic costs [2].

Low back pain (LBP) is a substantial health problem. It International guidelines for the management of LBP rec-
affects up to 80% of the adult population [1] and accounts ommend an initial triage to facilitate effective manage-
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(page number not for citation purposes)
BMC Musculoskeletal Disorders 2008, 9:11 http://www.biomedcentral.com/1471-2474/9/11
ment of the problem [3]. This classification process van Tulder et al. [20] evaluated the effect size of exercise
differentiates between specific spinal pathology, nerve based treatments for CNSLBP by relating the between
root pain and simple or non-specific low back pain group difference in outcome to the minimal clinically
(NSLBP) [4]. Most authorities suggest further staging the important difference (MCID) for that outcome. Of 37 tri-
problem by symptom duration into acute, sub acute or als analysed, only seven showed a clinically important
chronic [5-7]. NSLBP represents about 85% of LBP improvement in outcome. The same group performed a
patients seen in primary care [8] and the vast majority of meta-regression on trials of exercise for CNSLBP in an
LBP patients seen by physical therapists are classified attempt to determine the characteristics of exercise that
under this label. may optimise outcome from this intervention [21]. A
multivariate model including the most effective interven-
The prognosis for acute NSLBP (ANSLBP) is relatively tion characteristics had only a 4% chance of producing
favourable. A significant percentage of sufferers, probably clinically meaningful change in function when compared
over 50%, do not consult a health care professional for the to no treatment and a 1% chance of producing meaning-
problem [9]. Among those who do seek care, most will ful improvement in function when compared to other
experience rapid improvement in pain and disability conservative treatment. There was a 29% chance that the
within the first three months [10]. Beyond this time the expected improvements in pain would be clinically mean-
majority no longer consult and will continue to experi- ingful in comparison to no treatment and a 3% chance
ence only low levels of pain and disability, and most have when compared to other active treatment.
returned to work and their usual daily activities [10-12].
The disappointing results from clinical trials may be inter-
In a small group of acute patients, the problem fails to preted in two ways. Firstly, it is possible that the clinical
resolve as it should. Perhaps 10% will go on to develop trials are wrong. That is, for various reasons, the clinical
chronic, disabling LBP [12-14]. It is this group that utilises trial process fails to capture the reality of the clinical set-
the majority of resources allocated [11] and subsequently ting and underestimates the true effectiveness of current
there has been a considerable research effort to develop practice. Alternatively, the clinical trials are right and cur-
and evaluate effective treatments for this group. rent approaches to the management of CNSLBP are of
limited value.
Recent systematic reviews of the most commonly applied
treatments reach remarkably similar conclusions. Most The former perspective is one commonly taken by clini-
treatments provide small, short-term benefits when com- cians who feel the results of clinical trials are at odds with
pared to no treatment or sham treatment, but offer little their clinical experience. Numerous explanations have
benefit when compared to other forms of intervention been proffered, including insufficient treatment dose
[15]. No treatment seems to be superior to any other inter- [22], inappropriate patient selection [23,24], unsuitable
vention, including usual GP care [7,15-17]. Furthermore, treatment protocols [25] and outmoded treatment [26].
none of the cited interventions can be truly said to offer a Probably the most commonly encountered explanation
solution to the problem of chronic NSLBP (CNSLBP). relates to the perceived heterogeneity of the CNSLBP pop-
Although the magnitude of an individual's problem may ulation and the failure of research to adequately account
be reduced, the reduction is typically small and the prob- for this heterogeneity. Many authors feel that CNSLBP is
lem still persists [7,17,18]. made up of several distinct sub-groups, each reflecting dif-
ferent mechanisms of symptom production [27-29]. It is
Recent work evaluating the clinical importance of out- argued that the effects of treatment are diluted by the
come in CNSLBP reinforces this perspective. Keller et al application of a single intervention to a complex, hetero-
[19] calculated the effect sizes for a number of conserva- geneous group with diverse treatment needs [28-33]. The
tive interventions when compared to a no treatment con- consequence of this assertion is that sub-groups within
trol group. Acupuncture, exercise and psychological the CNSLBP population need to be identified to enable
treatment demonstrated moderate effect sizes for short- matching of the intervention with each specific mecha-
term pain relief. Small effect sizes were seen for manual nism [28,29,31,32]. This approach has within it the
therapy and electrical stimulation. Effect sizes for short- assumption that current interventions are appropriate and
term changes in function were small for exercise and psy- will ultimately be shown to be successful, if only they can
chological treatment. Long-term data were only presented be applied to the correct patient.
for exercise, which demonstrated small effect sizes for
both pain and function. They concluded that there is a The alternative interpretation, that the clinical trials are
dire need to develop more effective interventions for correct and current practice offers little benefit, is often
CNSLBP. neglected, and along with it the research agenda that
would have as its priority the development of new and
Page 2 of 15
novel models of care for CNSLBP. The purpose of this There is no doubt that CNSLBP represents a complex,
paper is to encourage clinicians to consider this alterna- multi-dimensional problem. The chronic LBP experience
tive. Particularly, that for management to move forward is characterised by a vast array of physical [40-42] and psy-
clinicians may need to regard CNSLBP in a very different chosocial [43,44] features. It is this complexity that is
way. We will attempt to do this in two ways. Firstly, we cited as a compelling argument for the existence of dis-
feel that the sub-grouping paradigm potentially stifles tinct mechanistic sub-groups within the CNSLBP popula-
engagement with this view and believe it is important that tion [31,45]. Complexity in presentation does not have to
clinicians and researchers more closely scrutinise the sub- be interpreted as evidence of distinct mechanisms. The lit-
grouping approach. Accordingly, the first section of the erature is replete with descriptions of the same degree of
discussion attempts to do this by considering possible physical and psychological intricacy within discrete dis-
weaknesses in the sub-grouping perspective. Secondly, an eases [46-52]. In these examples, the presence of a single
alternative model for understanding CNSLBP will be pre- disease gives rise to a host of physical and psychological
sented, which offers potential for very different ways of characteristics. As with LBP, these characteristics contrib-
managing the problem ute to the consequences of the problem to that individual.
The understanding of this complexity is vital in helping
Discussion personalise treatment and determining best how treat-
Sub-grouping is only one of a number of possible ment goals may be obtained for each patient. However,
explanations for the manifestations of CNSLBP there is a distinction between varying and personalising
What clinicians and researchers mean by a sub-group is individual care within a single framework and seeking dis-
not always clear. Sometimes it may refer to clustering of tinctly different modes of care.
effect modifiers within a distinct diagnostic group, what
may be referred to as a 'clinical sub-group'. Other times The multi-dimensional nature of CNSLBP may also be
the term is used to indicate groups with a unique mecha- interpreted in this way. While complexity in behaviour
nism or cause underlying the disorder, the terms 'aetiolog- can be explained by distinct mechanistic sub-groups, it
ical' or 'mechanistic sub-group' probably best capture this can equally be interpreted as the individualisation of
perspective. Both are seen in the LBP literature, for exam- response to a single underlying problem, and while the
ple the three major categories in the McKenzie approach complexity of the presentation requires that intervention
[34] can be thought of as mechanistic sub-groups, be broad and personalised it may still have as its basis a
whereas the sub-classifications of 'derangement' by direc- single idea.
tional preference and symptom distribution represent
clinical sub-groups under this single mechanistic Not only is CNSLBP complex, it is also possible to observe
umbrella. Likewise, O'Sullivan [35] has proposed three clustering of various characteristics in this population
broad mechanistic sub-groups for CLBP. These have simi- [31,33,53,54]. Historically, diagnosis has been driven by
larly been divided into clinical sub-groups; the broad aims labelling clusters of signs and symptoms [55] and in
of treatment are the same for each mechanistic sub-group CNSLBP it may be that these clusters represent different
though the specifics of intervention vary within the clini- mechanisms requiring different interventions [28]. How-
cal sub-classifications. It is mechanistic sub-grouping that ever, it is again worth considering other explanations.
is under discussion in this paper. Patients' presentations Researchers have repeatedly demonstrated grouping of
and responses to treatment will always vary and require characteristics in patients with specific disease processes.
personalisation of care. However, it is important to con- For example, patients with Parkinson's disease may be
sider if these variations need be interpreted as indicating stratified by rate of clinical progression [56] and individu-
distinctly different mechanisms underlying the disorder. als with sickle cell disease can be grouped by level of fear
avoidance [57]. Clustering of signs and symptoms will
The statistical problems and pitfalls of sub-grouping have almost always be possible within single disease entities.
been reviewed extensively in the literature [36-38]. How- One reason for this is variability in the severity of the con-
ever, other forms of bias in the construction of mechanis- dition. It is a reasonable prediction that those patients
tic sub-groups have been less often discussed. In whose condition is less severe will exhibit different signs,
particular, it is possible that a form of confirmatory bias symptoms and behaviours to those whose condition is
pervades aspects of the sub-grouping argument [39]. That moderate or those whose condition is severe. Clustering
is, explanations for the phenomena of LBP other than in presentation does not necessarily represent evidence of
sub-grouping are not considered. There are a number of separate mechanisms. Different mechanisms may explain
characteristics of the LBP experience that have prompted clustering, but equally it is possible to see and explain this
the proposition of a sub-grouping approach, and while phenomenon in problems with a single aetiology.
sub-grouping is consistent with these, it is worthwhile to
consider other potential explanations.
Page 3 of 15
Another consideration is the variability seen in clinical tri- Clinical studies on CNSLBP do not strongly support the
als of treatment for CNSLBP. Most commonly applied presence of mechanistic sub-groups
interventions have been subject to numerous studies, and Supporters of the sub-grouping model contend that the
for any given intervention it is possible to identify some small effect sizes seen in clinical trials result from the large
studies in which there is a demonstrated effect and others positive effects seen in some patients being 'washed out'
in which there is no effect. Failure to account for sub- by the smaller or negative effects seen in others [32]. The
groups within the LBP population has again been cited as solution offered for this problem is the matching of a
a potential explanation for these findings [38,32]. diagnostic profile with the type of intervention best suited
to that profile [32]. If this is the case there are a number of
There are several alternative explanations that are worth- reasonable predictions that can be made from the clinical
while contemplating. Firstly, statistical power may under- literature. Firstly, it would be expected that a treatment
pin some of the variability seen. The inconsistency does process that is derived from a patient examination and tai-
not necessarily reflect variability in treatment efficacy, just lored to the individual's presentation would be superior
variation in the statistical efficiency of studies to detect to a treatment process that is not. Secondly, multimodal
treatment effects. Secondly, there is likely to be some ran- care is likely to be superior to unimodal care as there is
dom error associated with a large number of studies. One less chance of 'washout' of treatment effect. Thirdly it
would expect to see most studies yield results representa- should be possible to identify groups of patients who
tive of the average effect of that intervention. Likewise, respond favourably to one form of treatment and less
there would be some variability in the response, with a favourably to alternative treatments.
few studies showing effects greater than the average and a
few studies showing effects lower than the average. The Specific versus non-specific treatments
variation may simply be noise, rather than variability Several different protocols have been used that compare
induced by "innovative trial design" [32]. Finally there is tailored to non-tailored treatment programmes, and all
some suggestion that authorship may influence the inter- reach similar conclusions. Comparisons between treat-
pretation of results. Variability in the outcome of clinical ment programmes based on individual patient assess-
trials may simply reflect different interpretations of effect ment and more general and generic treatment
sizes by authors [58,59], rather than evidence of bias in programmes demonstrate equivalence in outcome [60-
trial design or greater attention to sub-grouping. 68]. Providing therapists with the opportunity to assess
patients and provide them with the care they consider best
A further commonly applied argument for the pursuit of addresses the mechanism underpinning their disorder
mechanistic sub-groups is that NSLBP is too broad a cate- does not seem to be better than treatment that is generi-
gory. Researchers suggest that since the majority of low cally applied. Patients participating in general physical
back pain patients fall into this category, it's value in char- activity appear to do better than those engaged in specific
acterising a patient's presentation is only marginally more back exercises [69] and level of training and experience of
helpful than simply stating that they have pain in the back the therapist, presumably allowing more appropriate
[31,40]. NSLBP is indeed a broad category, representing matching of treatment with the patients' profile, seems
the vast majority of those who develop a complaint of not to impact on outcome [70]. Overall, there seems to be
back pain. However, CNSLBP represents only a small per- little support for the view that specific, individualised
centage of this population, probably less than 10% [12- treatment produces better outcome.
14]. It is a highly stratified group, representing that collec-
tion of patients whose symptoms were severe enough to Kent and colleagues [71] systematically evaluated this per-
warrant consultation, who had neither specific spinal spective for manual therapy using meta-analysis. Their
pathology nor nerve root pain and whose symptoms review compared the effects of manual therapy when ther-
failed to settle in the usual time frame. apists were free to select the intervention used, to studies
in which the manual therapy treatment was prescribed.
This section concludes that a number of the features of They were unable to detect any difference in outcome
CNSLBP can be explained by mechanisms other than the between these two conditions. Using a robust methodol-
inculcation of mechanistic sub-groups. This does not ogy, this group found no support for the perspective that
invalidate sub-grouping, it merely recognises that it is one individualised and clinically reasoned interventions are
of several alternatives. A more robust critique of the sub- superior to generically applied interventions.
grouping perspective requires consideration of the predic-
tions that a sub-grouping model makes, and investigation Hayden et al [21] compared outcome from individually
of data related to these predictions. This is the aim of the tailored exercise programmes, which presumably sought
next section. to address the mechanisms underlying a patient's disor-
der, to standardised programmes. Individually designed
Page 4 of 15
programmes had no effect on function in comparison to While acknowledging these problems, there is little evi-
general programmes and only a small and clinically dence from clinical studies of a patient profile that
unimportant influence on pain. responds uniquely to a given intervention. Pain intensity,
duration of the problem and distress appear repeatedly as
Unimodal versus multimodal care important predictors of outcome regardless of the type of
If the CNSLBP population contains distinct mechanistic treatment [30,90,92-96]. There is a sense that the charac-
sub-groups requiring different intervention strategies, teristics of patients who do poorly or well with treatment
then a reasonable prediction would be that multimodal are the same regardless of the intervention [92,93] and
interventions demonstrate superior outcomes to unimo- may simply be a reflection of severity. Unlike the situation
dal care, particularly when the unimodal components in ALBP [85,86,97] it has not yet been demonstrated that
have been shown to impart some benefit to patients. The the chronic population contains unique groups that
sub-grouping model would predict that subjects in multi- respond differently to different interventions.
modal care have a greater likelihood of receiving their
appropriate intervention, thus decreasing the chance of What else may explain the disappointing treatment
'washout'. While there is a possibility that treatments may results?
interact negatively, or in other complex ways, we consider In the previous sections we saw that the features of
this a reasonable prediction. While some papers show CNSLBP that have prompted clinicians and researchers to
small differences with the addition of treatments [72-74], consider sub-grouping may have alternate explanations
the majority of studies report no difference when unimo- and that clinical data on CNSLBP does not strongly sup-
dal and multimodal approaches are compared [68,75- port the presence of sub-groups. Despite its popularity,
84]. Increasing the likelihood that patients are exposed to sub-grouping may not be an important explanation for
the 'correct' treatment does not seem to enhance outcome. the disappointing results seen in clinical trials. An alterna-
tive perspective is that treatment has been ineffective
Hayden et al [21] again provide systematic and methodo- because it has been misdirected. One possible scenario is
logically rigorous information on this perspective. They that the problem of CNSLBP does not lie within the back,
compared exercise only groups with groups that received but within the brain. Thinking of CNSLBP as a problem of
exercise and additional therapy. The addition of other cortical reorganisation and degeneration may increase our
conservative care to exercise therapy for CLBP patients understanding of the problem and more appropriately
produced only small and clinically insignificant changes direct intervention.
in pain and function.
There is growing evidence that the brains of patients with
Sub-group response to treatment CNSLBP are different to those of normal subjects [98-102]
One approach to investigating sub-grouping in LBP is to and there are corresponding alterations in brain function
consider which cluster of patient factors identify those [99,103,104]. Herta Flor's group [99] provided the initial
most likely to benefit from a particular treatment. data in this area. They recorded evoked magnetic fields in
Research on ALBP, for example, has identified distinct and the brain in response to electrical stimulation of the back.
theoretically plausible clinical profiles that predict success They demonstrated greater reactivity in the primary som-
from manipulation [85] and stability training [86] and atosensory cortex (S1) and an expansion of the S1 repre-
preliminary evidence suggests that grouping patients this sentation of the back in CLBP patients. Altered S1
way makes a significant difference to outcome [87,88]. representation is also a feature of other complex pain
problems [105,106].
If CNSLBP is similarly made up of different mechanistic
subgroups, and a particular intervention is applied to the Recently investigators have looked more widely at brain
whole group, those patients that are matched to that treat- structure and function, and a consistent pattern of brain
ment should obtain benefit and their clinical profile changes has begun to emerge. Siddall et al. [101] used
ought to emerge from analyses of treatment moderators. magnetic resonance spectroscopy (MRS) to monitor bio-
There have been many attempts to elucidate the features chemical changes in the anterior cingulate cortex, prefron-
that influence outcome in CNSLBP patients receiving care. tal cortex and thalamus of 32 CLBP patients. This method
These data are difficult to interpret. The results are influ- was highly accurate in distinguishing CLBP patients from
enced by the type of outcome investigated and the follow- normal volunteers. Grachev et al. [100] also studied the
up interval [89]. In addition, there is great variability in biochemical profile of these three brain regions. They
the potential predictors that have been investigated, mak- looked at the concentrations of nine different metabolites
ing comparison and synthesis difficult [90] and interpre- using proton MRS. Again there was strong evidence for
tation is often confounded by lack of a comparison group alterations in the biochemical profile of CLBP patients,
[91]. most notable was evidence of neurodegeneration within
Page 5 of 15
the dorsolateral prefrontal cortex (DLPFC), a result repli- ventions, specifically designed to address putative
cated more recently in a group of depressed CLBP patients peripheral pathology, appear to offer little benefit to
[107]. patients [16,116,119]. Pain beyond the normal healing
time or in the absence of any meaningful peripheral
Brain morphometry has been used to investigate both pathology has long been a challenge in the understanding
general and regional gray matter density changes in CLBP of CNSLBP.
patients. Apkarian et al. [98] reported a greatly decreased
neocortical gray matter volume in patients compared to Sensitization of the nociceptive system is one suggested
matched controls. Regional analysis supported the bio- explanation for this problem. Enhanced synaptic effi-
chemical data, with the DLPFC showing the greatest ciency of nociceptive networks may facilitate the percep-
extent of loss. Less extensive gray matter loss was also tion of pain with little or no peripheral nociceptive input.
noted in the thalamus. Schmidt-Wilke et al. [102] also Evidence indicates that there is some degree of sensitisa-
found gray matter loss in the DLPFC of CLBP patients as tion in CNSLBP patients [99,120,121]. Theoretically, this
well as decreased volumes in S1 and the brainstem. This may be the result of changes in the periphery, the spinal
group also reported small increases in density in the tha- cord [122,123], the brain [124] or in a combination of
lamus and basal ganglia. Finally Honda et al. [108] these areas.
looked at cerebral blood flow in CLBP patients as part of
a larger study on diverse chronic pain states. Again the Studies of inflammatory and neuropathic pain models in
DLPFC featured, demonstrating decreased blood flow at animals demonstrate extensive structural and functional
rest. Decreased blood flow was also observed in the orbit- alterations in the dorsal horn of the spinal cord that rep-
ofrontal cortex and anterior cingulate cortex. resent a relatively specific degeneration of the inhibitory
interneurone system, leading to central sensitization and
Alteration in brain function may be the mechanism that increases in pain-related behaviours (for review see
underpins the problem of CNSLBP. The patterns of central [122]). Similar changes in the dorsal horn have been dem-
changes are consistent across a number of studies and onstrated post-mortem in human subjects who had suf-
methodologies and the extent of the central nervous sys- fered from post-herpetic neuralgia [125]. While it must be
tems changes are proportional to the duration and sever- considered that CNSLBP develops in the absence of
ity of the condition [98,99,102]. Indeed, Baliki et al. [109] demonstrable peripheral nerve injury it is possible that
suggest that brain changes account for over 70–80% of the the initial afferent nociceptive barrage that follows acute
variance for intensity and duration of CLBP. Cross-sec- spinal injury may induce lasting alterations in dorsal horn
tional studies always raise the problem of causality, and function that lead to the maintenance of pain after tissue
while there is no equivalent information on CNSLBP, healing has occurred.
some small longitudinal studies on other pain problems
characterised by altered cortical function suggest that Methodological barriers to studying cord structure and
interventions directed at cortical processing may be effec- function in humans make it difficult to ascertain the con-
tive [110-113], in two studies more effective than conven- tribution of such changes to CNSLBP. Furthermore, in
tional care [111,113]. Furthermore, good outcome is rodents, the spinal cord represents a far greater proportion
strongly related to normalisation of cortical function of the CNS than in humans, and animal models demon-
[114,115]. strate that while cord changes are prevalent in younger
animals, brain changes dominate in older animals [126].
A cortical model of CNSLBP must be able to explain the Nevertheless, the animal data is important as it suggests a
complex clinical presentation of the problem. Critical common aetiology of neurodegeneration. While there is
challenges include accounting for the innumerable physi- currently no evidence of spinal cord changes in CNSLBP
cal and psychological manifestations of CNSLBP and patients, there is significant data on altered brain function
offering an explanation for the equivalence in outcome of [99,103,121,124,127]. It could be argued that supraspinal
very disparate treatments. Though speculative, alteration changes may be more likely to drive the sensitised state
in brain function may offer some interesting perspectives seen in human subjects with CNSLBP.
and insights into these issues.
The work on brain changes in CLBP patients provides
Pain in the absence of meaningful spinal pathology speculative support for this view. Schmidt-Wilke et al.
There is now strong evidence that structural changes [102] demonstrated gray matter degeneration of the
within the spine have little meaning in the context of brainstem, an area highly associated with inhibitory pain
CNSLBP [18,116,117]. Recent evidence suggests that control, potentially leading to a loss of anti-nociception
structural abnormalities have little impact on the out- and the promotion of a sensitised state. There is also
come of conservative treatment [118] and invasive inter- strong evidence for the role of the DLPFC in pain modu-
Page 6 of 15
lation and inhibition. Activity in the DLPFC has been Lack of visual input of the moving part is a critical compo-
shown to be negatively correlated with pain intensity and nent of the incongruence hypothesis [132]. Vision has a
unpleasantness [128]. This area appears to have a role in dominant role over other senses in self-recognition, and
affective disengagement from pain [129] and activity in many studies demonstrate that body position sense is re-
this region is negatively correlated with the degree of pain calibrated to conform to visual information (for review
related catastrophising [130]. These functions are likely to see Jeannerod [136]). Thus the lumbar spine, which is not
be affected by the extensive DLPFC degeneration seen in directly visualised during task performance, may be more
CLBP. In support of this idea, Baliki et al. [109] have susceptible to this problem as abnormal cortical proprio-
shown that the sustained spontaneous pain of CLBP is ceptive representation cannot be 'corrected' by visual feed-
strongly associated with increased activity of the medial back.
pre-frontal cortex (mPFC) and suggest that this is the
result of a loss of inhibitory control of the mPFC from the Interestingly, conditions that generate sensory-motor con-
DLPFC. flict are associated with increased activation in the right
dorsolateral prefrontal cortex (DLPFC) [137]. As men-
A second proposition for the perception of pain in the tioned above structural neurodegeneration and altered
absence of spinal pathology is the presence of central pain activity of the DLPFC is a consistent finding in patients
memories. Flor [131] has suggested that the alterations in with CNSLBP [98,102,107], additionally a number of
sensory cortical representation found in chronic pain rep- studies have shown these changes are localised to the right
resent the neuronal substrate of implicit pain memories hemisphere [102,107]. Apkarian et al. [98] suggest excito-
that serve to maintain and enhance pain perceived in the toxicity secondary to long-term potentiation as a possible
affected body region. As well as providing a mechanism cause of this degeneration. One possible candidate for
for the maintenance of ongoing back pain, this may help inducing these changes is over-activation secondary to
to explain how previous episodes of low back pain lead to sensory-motor incongruence.
the development of chronicity, by contributing to and
reinforcing these pain memories. In summary, there are numerous ways whereby reorgani-
sation within the brain may generate persistent pain in the
An alternative mechanism has been proposed by which absence of ongoing peripheral pathology. These include,
cortical reorganisation may lead to the generation of reduced cortico-cortical and descending inhibition pro-
ongoing, movement related pain from within the brain. ducing an abnormally sensitised state, the reactivation of
Harris [132] suggests that altered cortical representation implicit pain memories, and centrally generated pain in
of somatic input may falsely signal incongruence between response to sensori-motor incongruence when the patient
motor intention and movement. The generation of motor moves the back. It is plausible that these mechanisms
activity within the central nervous system is closely cou- coexist. It is currently unknown to what extent that these
pled to sensory feedback systems, which are monitored to brain changes are reversible. Similar but distinct brain
detect any deviation from the predicted response [133]. If changes are noted in phantom limb pain and CRPS I, and
there is conflict between motor output and sensory feed- both these conditions appear amenable to treatment
back, it is hypothesised that pain is produced as a warning directed towards the brain [110-114]. If some of the
signal to alert the individual to abnormalities within changes noted are not reversible it might still be possible
information processing [133]. Alteration of the lumbar to alter pain by affecting processing within this altered sys-
spine's representation in S1 [99] may be the substrate of tem.
abnormal proprioceptive representation of the back and
therefore a possible source of sensory-motor incongru- Biomechanical manifestations of CNSLBP
ence. The biomechanical aspects of LBP have been widely inves-
tigated [138], and the range of mechanical manifestations
McCabe et al. [133] provided some experimental support seen in CNSLBP patients is vast. The back is moved less
for this hypothesis by inducing pain in healthy volunteers during functional tasks [139-143] and there is greater
moving in an environment that created a degree of sen- asymmetry and variability in performance [140,144,145].
sory-motor conflict. These results have attracted some crit- There is a consistent decrease in the velocity of movement
icism [134] and research using an alternative [146-148]. Muscles are activated in a dys-coordinated
methodology to disrupt cortical proprioceptive represen- manner in static and dynamic situations [149,150]. When
tation was unable to evoke pain [135]. It is worth consid- lifting, the back muscles are recruited earlier and stay on
ering that CNSLBP develops following an initial painful for longer and there is a greater amount of co-contraction
event and it is arguable that sensory-motor conflict may [151-153]. There are altered patterns of muscle recruit-
have more potential for generating pain when the pain ment with limb movements [154], with sudden loading
'matrix' is in a sensitised state. and unloading [155-158], and balance is impaired
Page 7 of 15
[157,159-162]. There is some suggestion of poorer prop- implicated in depressive disorders [178,179]. Although its
rioception [163-165] and there are delays in reaction precise role is currently not clearly defined [180,181], evi-
times to a variety of tasks [166-168]. dence points to primary abnormal activity within the
DLPFC [107]. Depressed CNSLBP patients have been
The congruence seen within these data is surprising. The shown to have evidence of DLPFC degeneration and the
overwhelming sense is a loss of confidence, control and level of degeneration was highly correlated with the level
coordination within the back. While Moseley and Hodges of depression [107]. One mechanism by which depressed
[169] contend that it is unclear if these abnormalities are mood influences chronicity may be via contributing to
compensatory, causative, neither or both, a common DLPFC degeneration.
approach is to interpret these findings as causative. Poor
stability and control is thought to influence loading of the Psychological variables also account for a significant
lumbar spine and sustain the production of peripheral amount of the variance in the CNSLBP condition [44].
nociceptive input [35,154,170,171]. Within this frame- Despite their explanatory value, the evidence for the effi-
work treatment is directed towards normalising motor cacy of psychologically based treatments is not strong.
performance based on a peripheral biomechanical model. Psychologically focused treatment only delivers small
However, it may be that these physical abnormalities are effects on pain and function when compared to no treat-
not causative but result from altered higher centre repre- ment [7]. They seem to be no more effective than other
sentation and the individual's attempts to maintain func- active interventions [7,117,182] and provide little addi-
tion with an altered body schema. It is conceivable that tional benefit when added to other conservative treatment
these features are epiphenomena of cortical dysfunction approaches [84,117,183]. The brain changes seen in
rather than the underlying mechanism of CNSLBP. If this CNSLBP may help explain this situation.
is the case treatment guided by a biomechanical explana-
tory model might be misdirected. The fear-avoidance model is seen as a central psychologi-
cal mechanism in the maintenance of CNSLBP [184,185].
Support for this view can be seen in a number of areas. Fundamental to this model are the opposing behavioural
There appears to be little association between changes in responses of confrontation and avoidance. Confrontation
patient centred outcome and changes in any aspect of low is seen as adaptive and likely to lead to resolution. Alter-
back related physical performance [117]. Lumbar stabili- natively, avoidance is thought to be maladaptive and con-
sation training programmes, which interpret these prob- tribute powerfully to the development of chronicity and
lems as causative and specifically address them from a numerous associated biological and psychological seque-
biomechanical perspective [172] and other active [173] lae [186]. Catastrophic beliefs and pain related fear are
and passive [174] interventions aimed at changing the primarily what drives avoidance [184], and are conse-
mechanical behaviour of the lower back demonstrate lim- quently seen as the primary targets for intervention. The
ited clinical effectiveness. origins of these beliefs are viewed as a major challenge in
developing the fear-avoidance model [186,187] and
Psychological manifestations of CNSLBP numerous possibilities have been suggested [184-187].
Psychological factors are an important part of the chronic
LBP experience. They contribute to the progression to One possible candidate for the genesis of these beliefs is
chronicity, explain a significant amount of the variance alteration in cortical representation of the back and result-
among CLBP patients and have been identified as impor- ant distorted body schema. Keefe et al [187] state that fear
tant barriers to resolution [44,175,176]. Alterations in may be fuelled by unexpected and novel bodily sensa-
brain function offer some additional insight into the role tions. Both McCabe et al. [133] and Moseley et al. [135]
psychological features play in the development of demonstrated that strangeness, foreignness and peculiar-
CNSLBP and the maintenance of the problem once it is ity are features of moving when there is sensory-motor
established. incongruence. As with the biomechanical features of
CNSLBP, fear and catastrophising may also be viewed as
Pincus et al. [175,176] cite distress/depressive mood as responses to an altered body schema. These beliefs would
integral psychological factors in the transition from acute be a reasonable response to an individual with an altered
to chronic LBP and several psychosocial models have cortical representation of their back who experiences
been postulated for the role of distress/depression in this unexplained pain and unexpected and novel sensations
transition [176,177]. Although speculative, brain reorgan- when moving. Treatments that seek to address these prob-
isation may also be significant. It appears that there is con- lems from a cognitive perspective may be less than ideal,
siderable overlap in the neural circuitries of the brain in as the fundamental substrate for the genesis of fear and
both depression and CLBP [107]. It is of particular interest catastrophisation would still be present.
that alteration of DLPFC function has been strongly
Page 8 of 15
It is also possible that degeneration within the DLPFC of CNSLBP. It is abundantly clear that the thoughts, feel-
may contribute directly to greater catastrophic interpreta- ings and beliefs of an individual impact significantly on
tion of pain. The DLPFC seems to be important in emo- the problem [4,44,191]. What may require reconsidera-
tional disengagement from pain [128,129] and it has tion is the origins of some maladaptive thoughts and
been proposed that degeneration of the DLPFC may con- beliefs and how these may be best modified.
tribute to the production of spontaneous pain [109],
which may fuel catastrophic thoughts, and, as discussed Figure 1. presents a speculative model for the develop-
above, there is evidence that DLPFC activity is negatively ment and maintenance of NSCLBP with altered cortical
correlated with catastrophic thinking about pain [130]. function at its core. In the model, current and previous
episodes of back pain contribute to an altered cortical rep-
Individuals' coping strategies are also considered to be resentation of the back. Conceivably, previous episodes of
important contributors to the disability associated with LBP may also increase distress about the problem. Altera-
CNSLBP. Active coping strategies, characterised by efforts tions in proprioceptive representation, subsequent sen-
to function in spite of pain or to distract oneself from pain sory-motor incongruence and pre-existing depressive
are thought to be important in adaptive functioning mood lead to over-activation and subsequent neurode-
[188]. Psychological management of CNSLBP seeks to use generative change in the DLPFC. Sensory-motor incongru-
distraction and encourages engagement in activity despite ence may also directly produce pain, sustain altered motor
pain, as part of the treatment process [189]. This requires control strategies and contribute to fear and catastrophic
that the individual is able to let task relevant stimuli to thoughts. The resulting DLPFC dysfunction contributes to
dominate over pain [128], which can be particularly diffi- central sensitization and subsequent ongoing and exag-
cult given the high attentional demands of pain [190]. gerated pain, and also decreases the patient's ability to dis-
One suggested role of the DLPFC is in governing efficient engage from the pain, thus feeding back into the negative
performance in the presence of interfering stimuli [128]. psychological influences. The mechanisms presented in
Degeneration of the DLPFC will obviously interfere with the model should be acknowledged as speculative but rep-
this ability. Patients may not respond to this component resent an attempt to interpret the alterations in brain func-
of treatment as the neural substrate for engagement in this tion that have been demonstrated in CNSLBP in light of
process is not available to them. These views do not chal- the clinical manifestations of the condition.
lenge the biopsychosocial approach to the management
Central
sensitisation
Previous LBP
‘cortical’ or Intra-/sub-cortical
pathological Facilitation / decreased
pain inhibition
Cortical
reorganisation
Change in cortical Change in

New episode internal body Sensory-motor
representation of Increased
of low back schema incongruence with Activation/LTP
Activation of somatosensory DLPFC mPFC activity
pain: Proprioceptive back movements of DLPFC
the central input degeneration
Peripheral deficiency and functional
pain
nociceptive (Inability of activities
neuromatrix Implicit pain
input vision to
memory formation
compensate)
Decreased Enhanced
Distress Motor control Feelings of disengagement spontaneous
Somatisation Depression changes foreignness and from pain pain
and Increased guarding peculiarity
hypervigilance and co contraction
Catastrophic
thoughts and
fear
Figure
A Cortical
1 Dysfunction Model of Chronic Non Specific Low Back Pain
A Cortical Dysfunction Model of Chronic Non Specific Low Back Pain. Abbreviations: LTP = Long Term Potentiation, DLPFC
= Dorsolateral Prefrontal Cortex, mPFC = medial Prefrontal Cortex.
Page 9 of 15
In summary, CNSLBP patients have back pain yet no con- ful to consider other possibilities. There is mounting evi-
servative or surgical pain relieving measures directed at dence for the effectiveness of alternative and innovative
the back appear effective. They display a number of bio- strategies for "re-training" cortical function in other com-
mechanical abnormalities, however treatment directed at plex, long standing, pain problems [110-114,193] as well
normalising lumbar biomechanics has little effect and as recent data that training of brain activation with func-
there is no relationship between changes in outcome and tional MRI can favourably influence chronic pain [194].
changes in spinal mechanics. Finally, these patients dem- Advances in non-invasive brain stimulation techniques
onstrate some psychological problems but psychologi- such as repetitive transcranial magnetic stimulation and
cally based treatments offer only partial solution to the transcranial direct current stimulation also offer
problem. A possible explanation for these findings is that approaches for altering cortical function to achieve pain
they are epiphenomena, features that are incidental to a relief [195,196] and to enhance cognitive function [197-
problem of neurological reorganisation and degenera- 199]. The challenge presented by this model for research-
tion. ers and clinicians is to determine how therapy might be
designed to address cortical function.
Equivalence of treatment effects
As discussed, the response of CNSLBP patients is very sim- In conclusion there is little evidence to endorse current
ilar across a broad range of treatment options. A simple treatment for CNSLBP. Most treatments provide only
explanation would be to conclude that current interven- small short-term changes and there is currently scant evi-
tions are ineffective or demonstrate only non-specific or dence that one form of treatment is superior to another.
placebo effects. However, the evidence does not support Sub-grouping of CNSLBP is a common response to these
either of these perspectives. Most commonly applied con- disappointing results. The sub-grouping perspective is not
servative treatments demonstrate some level of effective- consistently supported by the available data and it is
ness, albeit small, and this seems to be above what is important that other research agendas are entertained. An
produced by sham treatment [15]. Alternatively, disparate alternative perspective is that treatment has been ineffec-
treatments may demonstrate equivalence in outcome tive because it has been misdirected. CNSLBP may be a
because they all work through the same mechanism. Mas- problem of abnormal cortical function. There is growing
sage, manipulation, exercise, acupuncture, education and evidence of supraspinal abnormalities in CNSLBP, these
other interventions may work by influencing cortical mechanisms can potentially explain the complexity of the
function. The effectiveness is comparable across treat- LBP experience and the outcomes of clinical trials on
ments because the pathway by which they act may be the CNSLBP. Various research groups have demonstrated the
same. potential value of 'training the brain' in other conditions
characterised by abnormal cortical processing. Given the
This perspective may also explain the disappointing effect growing body of evidence indicating similar neural mech-
sizes seen with conservative care. A possible reason for the anisms in CNSLBP, the development of clinical strategies
small effects seen is that none of these interventions are targeted at normalising neurological processing represents
currently delivered in a way that focuses on central a challenging new direction for musculoskeletal clinicians
processing. Mobilisation of the lumbar spine might be and researchers involved in the management of CNSLBP.
made more cortically directed by having the patient
respond verbally to the stimulus, trying to localise the Summary
level or determine direction of pressure, akin to the sen- • Clinical trials offer little support for current manage-
sory discrimination task employed by Flor et al. [114] in ment of chronic non specific low back pain
managing phantom limb pain or by Moseley et al. [192]
in CRPS. Exercises aimed at improving trunk muscle • Sub-grouping has been commonly offered as an expla-
recruitment seem an ideal way to normalise cortical repre- nation for the disappointing results of clinical trials
sentation, but rather than emphasis being placed on per-
forming a particular type of muscle recruitment pattern • Much of the literature on CNSLBP do not strongly sup-
based on a peripheral biomechanical model port a sub-grouping model
[154,170,171] participation in a variety of challenging
exercises may be more useful. Simply mastering any skill • Evidence is emerging of significant cortical alterations in
that the patient finds difficult may be all that is required. CNSLBP patients
Similar thinking can be applied to most commonly These changes may offer an explanation for the complex
applied conservative interventions, and whilst changing problem of CLBP and a potential focus for effective treat-
the emphasis of existing treatments may be a viable ment.
option for enhancing clinical efficacy, it may also be use-
Page 10 of 15
Competing interests for chronic low back pain as example. Spine 2007,
32:16:1785-1790.
The author(s) declare that they have no competing inter- 21. Hayden JA, Van Tulder MW, Tomlinson G: Systematic Review:
ests. Strategies for using exercise therapy to improve outcome in
chronic low back pain. Ann Intern Med 2005, 142(9):766-785.
22. Jull G, Moore A: What is a Suitable Dosage of Physical Therapy
Authors' contributions Treatment? Manual Therapy 2002, 7:4:181-182.
Both authors contributed to the development of the ideas 23. Ott SM: Physical therapy, chiropractic manipulation, or an
and arguments within this manuscript. Both authors have educational booklet for back pain. N Engl J Med 1999,
340(5):389-390.
read and approved the manuscript 24. Freeman MD, Rossignol AM: A critical evaluation of the meth-
odology of a low-back pain clinical trial. J Manipulative Physiol
Ther 2000, 23(5):363-364.
Acknowledgements 25. Rosner A: Fables or foibles: inherent problems with RCTs. J
The authors wish to thank Dr James McAuley, David Maskill, Pam Gerrard, Manipulative Physiol Ther 2003, 26:460-46.
Keith Smart, Claire Bourgoin, Carol McCrum and Dr Lorimer Moseley for 26. Moore A, Jull G: The systematic review of systematic reviews
their comments on earlier drafts of this manuscript. has arrived! Manual Therapy 2006, 11:91-92.
27. Dankaerts W, O'Sullivan PB, Straker LM, Burnett AF, Skouen JS: The
inter-examiner reliability of a classification method for non-
References specific chronic low back pain patients with motor control
1. Walker BF, Muller R, Grant WD: Low back pain in Australian impairment. Manual Therapy 2006, 11:1:28-39.
adults. Health provider utilization and care seeking. J Manip 28. Delitto A: Research in low back pain: Time to stop seeking the
Physiol Ther 2004, 27:327-335. elusive "magic bullet". Phys Ther 2005, 85:206-208.
2. Maniadakis N, Gray A: The economic burden of back pain in the 29. Leboeuf-Yde C, Manniche C: Low back pain: Time to get off the
UK. Pain 2000, 84:95-103. treadmill. J Manip Physiol Ther 2001, 24:63-66.
3. Koes BW, van Tulder MW, Ostelo R, Kim Burton A, Waddell G: 30. Leboeuf-Yde C, Grønstvedt A, Borge JA, Lothe J, Magnesen E, Nilsson
Clinical guidelines for the management of low back pain in O, Rosok G, Stig LC, Larsen K: The nordic back pain subpopula-
primary care: an international comparison. Spine 2001, tion program: Demographic and clinical predictors for out-
26:2504-13. come in patients receiving chiropractic treatment for
4. Waddell G: The Back Pain Revolution Edinburgh: Churchill Livingstone; persistent low-back pain. J Manip Physiol Therap 2004, 27:493-502.
2004. 31. McCarthy J, Arnall A, Strimpakos N, Freemont A, Oldham J: The
5. Spitzer WO, LeBlanc FE, Dupuis M: Scientific approach to the biopsychosocial classification of non-specific low back pain: a
assessment and management of activity related spinal disor- systematic review. Phys Ther Rev 2004, 9:17-30.
ders: a monograph for clinicians. Report of the Quebec task 32. McCarthy CJ, Cairns MC: Why is the recent research regarding
force on spinal disorders. Spine 1987, 12:S1-S60. non-specific pain so non-specific? Manual Therapy 2005,
6. Merskey H, Bogduk N: Classification of chronic pain Seattle: IASP Press; 10:239-241.
1994. 33. Turk DC: The potential of treatment matching for subgroups
7. Bogduk N, McGuirk B: Medical Management of Acute and Chronic Low of patients with chronic pain: Lumping versus splitting. Clin J
Back Pain: An Evidence-based Approach Elsevier; 2002. Pain 2005, 21:44-55.
8. Deyo RA, Phillips WR: Low back pain: A primary care chal- 34. McKenzie RA, May S: Mechanical diagnosis and therapy: the lumbar spine
lenge. Spine 1996, 21:2826-2832. 2nd edition. Waikanae: Spinal Publications; 2003.
9. Waxman R, Tennant A, Helliwell P: Community survey of factors 35. O'Sullivan P: Diagnosis and classification of chronic low back
associated with consultation for low back pain. BMJ 1998, pain disorders: Maladaptive movement and motor control
317:1564-1567. impairments as underlying mechanism. Manual Therapy 2005,
10. Pengel LHM, Herbert RD, Maher CG, Refshauge KM: Acute low 10:242-255.
back pain: Systematic review of its prognosis. BMJ 2003, 36. Herbert R: Dealing with heterogeneity in clinical trials. Manual
327:323-325. Therapy 2007, 12:1:1-2.
11. Kent PM, Keating JL: The epidemiology of low back pain in pri- 37. Cook DI, Gebski VJ, Keech AC: EBM: Trials on Trial. Subgroup
mary care. Chiropractic and Osteopathy 2005, 13:13. analysis in clinical trials. Med J Aust 2004, 180:6:289-291.
12. Carey TS, Garrett JM, Jackman AML: Beyond the good prognosis: 38. Yusuf S, Wittes J, Probstfield J, Tyroler HA: Analysis and interpre-
Examination of an inception cohort of patients with chronic tation of treatment effects in subgroups of patients in rand-
low back pain. Spine 2000, 25:1:115-120. omized clinical trials. JAMA 1991, 266:1:93-98.
13. Klenerman L, Slade PD, Stanley IM, Pennie B, Reilly JP, Atchison LE, 39. Klein JG: Five pitfalls in decisions about diagnosis and pre-
Troup JDG, Rose MJ: The prediction of chronicity in patients scribing. BMJ 2005, 330:7494:781-3.
with an acute attack of low back pain in a general practice 40. McGregor AH, McCarthy ID, Hughes SPF: Motion characteristics
setting. Spine 1995, 20(4):478-484. of normal subjects and people with low back pain. Physiother-
14. Van Den Hoogen HJM, Koes BW, Van Eijk JTM, Bouter LM, Deville' apy 1995, 81:632-637.
W: On the course of low back pain in general practice: A one 41. O'Sullivan PB, Twomey L, Allison CT: Dysfunction of the neuro-
year follow up study. Annals of the Rheumatic Diseases 1998, muscular system in the presence of low back pain-Implica-
57:13-19. tions for physical therapy management. J Man Manip Ther 1997,
15. van Tulder MW, Koes B, Malmivaara A: Outcome of non-invasive 5:20-26.
treatment modalities on back pain: an evidence-based 42. Van Dieën JH, Selen LPJ, Cholewicki J: Trunk muscle activation in
review. Eur Spine J 2006, 15: Suppl 1:S64-81. low-back pain patients, an analysis of the literature. J Electro-
16. van Tulder MW, Koes B, Seitsalo S, Malmivaara A: Outcome of myog Kinesiol 2003, 13:333-351.
invasive treatment modalities on back pain and sciatica: an 43. Main CJ, Watson PJ: Psychological aspects of pain. Manual Ther-
evidence-based review. Eur Spine J 2006, 15: Suppl 1:S82-92. apy 1999, 4:203-215.
17. Bogduk N: Management of chronic low back pain. Med J Aust 44. Linton SJ: A review of psychological risk factors in back and
2004, 180:79-83. neck pain. Spine 2000, 25:1148-1156.
18. Koes BW, Van Tulder MW, Thomas S: Diagnosis and treatment 45. McCarthy CJ: There is no panacea for low back pain. Physiother-
of low back pain. BMJ 2006, 332:1430-1434. apy 2005, 91:1:2-3.
19. Keller A, Hayden J, Bombardier C, van Tulder M: Effect sizes of 46. Andenaes R, Kalfoss M, Wahl A: Psychological distress and qual-
non-surgical treatments of non-specific low-back pain. Eur ity of life in hospitalized patients with chronic obstructive
Spine J 2007, 16:11:1776-88. pulmonary disease. J Advanced Nursing 2004, 46:523-530.
20. Van Tulder M, Malmivaara A, Hayden J, Koes B: Statistical signifi- 47. Bostan EE, Borman P, Bodur H, Barça N: Functional disability and
cance versus clinical importance: Trials on exercise therapy quality of life in patients with ankylosing spondylitis. Rheuma-
tol Int 2003, 23:121-126.
Page 11 of 15
48. Evers AWM, Kraaimaat FW, Geenen R, Jacobs JWG, Bijlsma JWJ: 68. The UK BEAM Trial Team: United Kingdom back pain exercise
Longterm predictors of anxiety and depressed mood in early and manipulation (UKBEAM) randomised trial: effectiveness
rheumatoid arthritis: A 3 and 5 year follow up. J Rheum 2002, of physical treatments for back pain in primary care. BMJ
29:2327-2336. 2004, 11:329(7479):1377.
49. Hyphantis T, Kaltsouda A, Triantafillidis J, Platis O, Karadagi S, Chris- 69. Hurwitz EL, Morgenstern H, Chiao C: Effects of recreational
tou K, Mantas C, Argyropoulos A, Mavreas V: Personality corre- physical activity and back exercises on low back pain and psy-
lates of adherence to type 2 diabetes regimens. Int J Psychiatry chological distress: Findings from the UCLA low back pain
Med 2005, 35:103-107. study. Am J Pub Health 2005, 95:1817-1824.
50. Petrie KJ, Weinman J, Sharpe N, Buckley J: Role of patients' view 70. Whitman JM, Fritz JM, Childs JD: The influence of experience and
of their illness in predicting return to work and functioning specialty certifications on clinical outcomes for patients with
after myocardial infarction: Longitudinal study. BMJ 1996, low back pain treated within a standardized physical therapy
312:1191-1194. management program. J Orthop Sports Phys Ther 2004,
51. Smedstad LM, Moum T, Vaglum P, Kvien TK: The Impact of Early 34:662-672.
Rheumatoid Arthritis on Psychological Distress: A compari- 71. Kent P, Marks D, Pearson W, Keating J: Does clinician treatment
son between 238 patients with RA and 116 matched con- choice improve the outcome of manual therapy for nonspe-
trols. Scand J Rheumatol 1996, 25:377-382. cific low back pain? A metaanalysis. J Manip Physiol Ther 2005,
52. Yeh M, Chen H, Liao Y, Liao W: Testing the functional status 28:312-322.
model in patients with chronic obstructive pulmonary dis- 72. Bendix AF, Bendix T, Lund C, Kirkbak S, Ostenfeld S: Comparison
ease. J Advanced Nursing 2004, 48:342-350. of three intensive programs for chronic low back pain
53. Riddle DL: Classification and low back pain: A review of the lit- patients: A prospective, randomized, observer-blinded study
erature and critical analysis of selected systems. Phys Ther with one-year follow-up. Scand J Rehab Med 1997, 29(2):81-89.
1998, 78:708-737. 73. Jousset N, Fanello S, Bontoux L, Dubus V, Billabert C, Vielle B, Roque-
54. Peterson T, Thorsen H, Manniche C, Ekdahl C: Classification of laure Y, Penneau-Fontbonne D, Richard I: Effects of Functional
nonspecific low back pain. A review of the literature on clas- Restoration Versus 3 Hours per Week Physical Therapy: A
sification systems relevant to physiotherapy. Phys Ther Rev Randomized Controlled Study. Spine 2004, 29:487-493.
1999, 4:265-281. 74. Molsberger AF, Mau J, Pawelec DB, Winkler JA: Does acupuncture
55. Zimny NJ: Diagnostic classification and orthopaedic physical improve the orthopedic management of chronic low back
therapy practice: what we can learn from medicine. J Orthop pain – A randomized, blinded, controlled trial with 3 months
Sports Phys Ther 2004, 34(3):105-109. follow up. Pain 2002, 99:579-587.
56. Schrag A, Dodel R, Spottke A, Bornschein B, Siebert U, Quinn NP: 75. Bendix T, Bendix A, Labriola M, Haestrup C, Ebbehoj N: Functional
Rate of clinical progression in Parkinson's disease: A pro- restoration versus outpatient physical training in chronic low
spective study. Mov Disord 2007, 22:7:938-45. back pain. A randomized comparative study. Spine 2000,
57. Pells J, Edwards CL, McDougald CS, Wood M, Barksdale C, Jonassaint 25:2494-2500.
J, Leach-Beale B, Byrd G, Mathis M, Harrison MO, Feliu M, Edwards 76. Bronfort G, Goldsmith CH, Nelson CF, Boline PD, Anderson AV:
LY, Whitfield KE, Rogers L: Fear of Movement (Kinesiophobia), Trunk exercise combined with spinal manipulative or
Pain, and Psychopathology in Patients With Sickle Cell Dis- NSAID therapy for chronic low back pain: A randomized,
ease. Clin J Pain 2007, 23(8):707-713. observer-blinded clinical trial. J Manipulative Physiol Ther 1996,
58. Canter PH, Ernst E: Sources of bias in reviews of spinal manip- 19:570-582.
ulation for back pain. Wien Klin Wochenschr 2005, 117:333-341. 77. Cairns MC, Foster NE, Wright C: Randomized controlled trial of
59. Smith LA, Oldman AD, McQuay HJ, Moore RA: Teasing apart specific spinal stabilization exercises and conventional phys-
quality and validity in systematic reviews: An example from iotherapy for recurrent low back pain. Spine 2006,
acupuncture trials in chronic neck and back pain. Pain 2000, 31:19:E670-E681.
86:119-132. 78. Hsieh CJ, Adams AH, Tobis J, Hong CZ, Danielson C, Platt K, Hoeh-
60. Critchley DJ, Ratcliffe J, Noonan S, Jones RH, Hurley MV: Effective- ler F, Reinsch S, Rubel : Effectiveness of four conservative treat-
ness and cost-effectiveness of three types of physiotherapy ments for subacute low back pain: A randomized clinical
used to reduce chronic low back pain disability: a pragmatic trial. Spine 2002, 27:1142-1148.
randomized trial with economic evaluation. Spine 2007, 79. Hurwitz EL, Morgenstern H, Harber P, Kominski GF, Belin TR, Yu F,
15:1474-81. Adams AH: A randomized trial of medical care with and with-
61. Carr JL, Klaber Moffett JA, Howarth E, Richmond SJ, Torgerson DJ, out physical therapy and chiropractic care with and without
Jackson DA, Metcalfe CJ: A randomized trial comparing a group physical modalities for patients with low back pain: 6-month
exercise programme for back pain patients with individual follow-up outcomes from the UCLA low back pain study.
physiotherapy in a severely deprived area. Disabil Rehabil 2005, Spine 2002, 15:27(20):2193-204.
27:929-937. 80. Kääpä EH, Frantsi K, Sarna S, Malmivaara A: Multidisciplinary
62. Frost H, Lamb SE, Doll HA, Carver PT, Stewart-Brown S: Ran- group rehabilitation versus individual physiotherapy for
domised controlled trial of physiotherapy compared with chronic nonspecific low back pain: A randomized trial. Spine
advice for low back pain. BMJ 2004, 329:708-711. 2006, 31:371-376.
63. Geisser ME, Wiggert EA, Haig AJ, Colwell MO: A randomized, 81. Kainz B, Gülich M, Engel E, Jäckel WH: Comparison of three out-
controlled trial of manual therapy and specific adjuvant patient therapy forms for treatment of chronic low back
exercise for chronic low back pain. Clin J Pain 2005, 21:463-470. pain – Findings of a multicentre, cluster randomized study.
64. Hay EM, Mullis R, Lewis M, Vohora K, Main CJ, Watson P, Dziedzic Rehabilitation 2006, 45:65-77.
KS, Sim J, Minns Lowe C, Croft PR: Comparison of physical treat- 82. Koumantakis GA, Watson PJ, Oldham JA: Trunk muscle stabiliza-
ments versus a brief pain-management programme for back tion training plus general exercise versus general exercise
pain in primary care: A randomised clinical trial in physio- only: Randomized controlled trial of patients with recurrent
therapy practice. Lancet 2005, 365:2024-2030. low back pain. Phys Ther 2005, 85:209-225.
65. Lewis JS, Hewitt JS, Billington L, Cole S, Byng J, Karayiannis S: A ran- 83. Linton SJ, Boersma K, Jansson M, Svärd L, Botvalde M: The effects
domized clinical trial comparing two physiotherapy inter- of cognitive-behavioral and physical therapy preventive
ventions for chronic low back pain. Spine 2005, 30:711-721. interventions on pain-related sick leave: A randomized con-
66. Mannion AF, Müntener M, Taimela S, Dvorak J: A randomized clin- trolled trial. Clin J Pain 2005, 21:109-119.
ical trial of three active therapies for chronic low back pain. 84. Smeets RJEM, Vlaeyen JWS, Hidding A, Kester AD, van der Heijden
Spine 1999, 24:2435-2448. GJ, van Geel AC, Knottnerus JA: Active rehabilitation for chronic
67. Petersen T, Kryger P, Ekdahl C, Olsen S, Jacobsen S: The effect of low back pain: Cognitive-behavioral, physical, or both? First
McKenzie therapy as compared with that of intensive direct post-treatment results from a randomized controlled
strengthening training for the treatment of patients with trial. BMC Musculoskel Disord 2006, 7:5.
subacute or chronic low back pain: A randomized controlled 85. Flynn T, Fritz J, Whitman J, Wainner R, Magel J, Rendeiro D, Butler B,
trial. Spine 2002, 27:1702-1708. Garber M, Allison S: A clinical prediction rule for classifying
patients with low back pain who demonstrate short-term
Page 12 of 15
improvement with spinal manipulation. Spine 2002, 104. Small DM, Apkarian AV: Increased taste intensity perception
27:2835-2843. exhibited by patients with chronic back pain. Pain 2006,
86. Hicks GE, Fritz JM, Delitto A, McGill SM: Preliminary develop- 120:124-130.
ment of a clinical prediction rule for determining which 105. Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N,
patients with low back pain will respond to a stabilization Larbig W, Taub E: Phantom-limb pain as a perceptual correlate
exercise program. Arch Phys Med Rehab 2005, 86:1753-1762. of cortical reorganization following arm amputation. Nature
87. Childs JD, Fritz JM, Flynn TW, Irrgang JJ, Johnson KK, Majkowski GR, 1995, 375:6531:482-4.
Delitto A: A clinical prediction rule to identify patients with 106. Maihöfner C, Handwerker HO, Neundörfer B, Birklein F: Patterns
low back pain most likely to benefit from spinal manipula- of cortical reorganization in complex regional pain syn-
tion: A validation study. Ann Intern Med 2004, 141(12):920-928. drome. Neurology 2003, 61(12):1707-1715.
88. Fritz JM, Whitman JM, Childs JD: Lumbar spine segmental mobil- 107. Grachev ID, Ramachandran TS, Thomas PS, Szeverenyi NM, Fredrick-
ity assessment: an examination of the validity for determin- son BE: Association between dorsolateral prefrontal N-acetyl
ing intervention strategies in patients with low back pain. aspartate and depression in chronic back pain: An in vivo
Arch Phys Med Rehabil 2005, 86(9):1745-1752. proton magnetic resonance spectroscopy study. J Neural
89. McCracken LM, Turk DC: Behavioral and cognitive-behavioral Transm 2003, 110:287-312.
treatment for chronic pain: Outcome, predictors of out- 108. Honda T, Maruta T, Takahashi K: Brain perfusion abnormality in
come, and treatment process. Spine 2002, 27:2564-2573. patients with chronic pain. Keio J Med 2007, 56:2:48-52.
90. Van Der Hulst M, Vollenbroek-Hutten MMR, Ijzerman MJ: A system- 109. Baliki MN, Chialvo DR, Geha PY, Levy RM, Harden RN, Parrish TB,
atic review of sociodemographic, physical, and psychological Apkarian AV: Chronic pain and the emotional brain: Specific
predictors of multidisciplinary rehabilitation- or, back school brain activity associated with spontaneous fluctuations of
treatment outcome in patients with chronic low back pain. intensity of chronic back pain. J Neurosci 2006, 26:12165-12173.
Spine 2005, 30:813-825. 110. McCabe CS, Haigh RC, Ring EFJ, Halligan PW, Wall PD, Blake DR: A
91. Riipinen M, Niemistö L, Lindgren K, Hurri H: Psychosocial differ- controlled pilot study of the utility of mirror visual feedback
ences as predictors for recovery from chronic low back pain in the treatment of complex regional pain syndrome (type
following manipulation, stabilizing exercises and physician 1). Rheumatology 2003, 42:97-101.
consultation or physician consultation alone. J Rehab Med 111. Moseley GL: Graded motor imagery is effective for long-
2005, 37(3):152-158. standing complex regional pain syndrome: A randomised
92. Underwood MR, Morton V, Farrin A, on behalf of the UK BEAM trial controlled trial. Pain 2004, 108:192-198.
team: Do baseline characteristics predict response to treat- 112. Moseley GL: Is successful rehabilitation of complex regional
ment for low back pain? Secondary analysis of the UK BEAM pain syndrome due to sustained attention to the affected
dataset. Rheumatology 2007, 46:1297-1302. limb? A randomised clinical trial. Pain 2005, 114(1–2):54-61.
93. Skargren EI, Öberg BE: Predictive factors for 1-year outcome of 113. Moseley GL: Graded motor imagery for pathologic pain: a ran-
low-back and neck pain in patients treated in primary care: domized controlled trial. Neurology 2006, 67:12:2129-34.
Comparison between the treatment strategies chiropractic 114. Flor H, Denke C, Schaefer M, Grüsser S: Effect of sensory discrim-
and physiotherapy. Pain 1998, 77:201-207. ination training on cortical reorganisation and phantom limb
94. Bekkering GE, Hendriks HJ, Van Tulder MW, Knol DL, Simmonds MJ, pain. Lancet 2001, 357:1763-1764.
Oostendorp RA, Bouter LM: Prognostic factors for low back 115. Maihöfner C, Handwerker HO, Neundörfer B, Birklein F: Cortical
pain in patients referred for physiotherapy: Comparing out- reorganization during recovery from complex regional pain
comes and varying modeling techniques. Spine 2005, syndrome. Neurology 2004, 63(4):693-701.
30:1881-1886. 116. Carragee EJ, Hannibal M: Diagnostic evaluation of low back pain.
95. Michaelson P, Sjölander P, Johansson H: Factors predicting pain Orthop Clin N Am 2004, 35:7-16.
reduction in chronic back and neck pain after multimodal 117. COST B13 Working Group on Guidelines for Chronic Low
treatment. Clin J Pain 2004, 20:447-454. Back Pain: European guidelines for the management of non-
96. Niemistö L, Sarna S, Lahtinen-Suopanki T, Lindgren K, Hurri H: Pre- specific low back pain 2004 [http://www.backpaineurope.org/web/
dictive factors for 1-year outcome of chronic low back pain files/WG2_Guidelines.pdf].
following manipulation, stabilizing exercises, and physician 118. Kleinstück F, Dvorak J, Mannion AF: Are "structural abnormali-
consultation or physician consultation alone. J Rehab Med ties" on magnetic resonance imaging a contraindication to
2004, 36:104-109. the successful conservative treatment of chronic nonspecific
97. Jellema P, Van Der Horst HE, Vlaeyen JWS, Stalman WAB, Bouter low back pain? Spine 2006, 31:2250-2257.
LM, Van Der Windt DAWM: Predictors of outcome in patients 119. Carragee EJ, Lincoln T, Parmar VS, Alamin T: A gold standard eval-
with (sub)acute low back pain differ across treatment uation of the "discogenic pain" diagnosis as determined by
groups. Spine 2006, 31:1699-1705. provocative discography. Spine 2006, 31:18:2115-23.
98. Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB, Gitel- 120. Clauw DJ, Williams D, Lauerman W, Dahlman M, Aslami A, Nachem-
man DR: Chronic back pain is associated with decreased pre- son AL, Kobrine AI, Wiesel SW: Pain sensitivity as a correlate of
frontal and thalamic gray matter density. J Neurosci 2004, clinical status in individuals with chronic low back pain. Spine
24:10410-10415. 1999, 24:19:2035-41.
99. Flor H, Elbert T, Braun C, Birbaumer N: Extensive cortical reor- 121. Giesecke T, Gracely RH, Grant MAB, Nachemson A, Petzke F, Wil-
ganization in chronic back pain patients. NeuroImage 1997, liams DA, Clauw DJ: Evidence of Augmented Central Pain
5(4):S216. Processing in Idiopathic Chronic Low Back Pain. Arthritis
100. Grachev ID, Fredrickson BE, Apkarian AV: Abnormal brain chem- Rheum 2004, 50:613-623.
istry in chronic back pain: An in vivo proton magnetic reso- 122. Apkarian AV, Scholz J: Shared mechanisms between chronic
nance spectroscopy study. Pain 2000, 89:7-18. pain and neurodegenerative disease. Drug Discovery Today: Dis-
101. Siddall PJ, Stanwell P, Woodhouse A, Somorjai RL, Dolenko B, Nikulin ease Mechanisms 2006, 3:3:319-326.
A, Bourne R, Himmelreich U, Lean C, Cousins MJ, Mountford CE: 123. Thompson S: Clinical Pain, experimental evidence: Molecular
Magnetic resonance spectroscopy detects biochemical mechanisms within the spinal cord. In Topical Issues in Pain 5
changes in the brain associated with chronic low back pain: Edited by: Gifford L. Falmouth: CNS Press; 2005:379-397.
A preliminary report. Anesthesia Analgesia 2006, 102:1164-1168. 124. Flor H: Cortical reorganisation and chronic pain: Implications
102. Schmidt-Wilcke T, Leinisch E, Gänßbauer S, Draganski B, Bogdahn U, for rehabilitation. J Rehab Med, Supplement 2003:66-72.
Altmeppen J, May A: Affective components and intensity of pain 125. Watson CPN, Deck JH, Morshead C, Van der Kooy D, Evans RJ:
correlate with structural differences in gray matter in Post-herpetic neuralgia: Further post-mortem studies of
chronic back pain patients. Pain 2006, 125:89-97. cases with and without pain. Pain 1991, 44:2:105-117.
103. Giesecke T, Gracely RH, Clauw DJ, Nachemson A, Duck MH, 126. Flor H, Nikolajsen L, Jensen TS: Phantom limb pain: A case of
Sabatowski R, Gerbershagen HJ, Williams DA, Petzke F: Central maladaptive CNS plasticity? Nature Reviews Neuroscience 2006,
pain processing in chronic low back pain: Evidence for 7:11:873-881.
reduced pain inhibition. Schmerz 2006, 20:411-417.
Page 13 of 15
127. Grachev ID, Fredrickson BE, Apkarian AV: Brain chemistry back pain patients and asymptomatic participants during lift-
reflects dual states of pain and anxiety in chronic low back ing exertions. Clin Biomech 2004, 19:992-999.
pain. J Neural Transm 2002, 109:1309-1334. 152. Marras WS, Davis KG, Ferguson SA, Lucas BR, Gupta P: Spine load-
128. Lorenz J, Minoshima S, Casey KL: Keeping pain out of mind: The ing characteristics of patients with low back pain compared
role of the dorsolateral prefrontal cortex in pain modulation. with asymptomatic individuals. Spine 2001, 26:2566-2574.
Brain 2003, 126:1079-1091. 153. Marras WS, Ferguson SA, Burr D, Davis KG, Gupta P: Spine loading
129. Schmahl C, Bohus M, Esposito F, Treede RD, Di Salle F, Greffrath W, in patients with low back pain during asymmetric lifting
Ludaescher P, Jochims A, Lieb K, Scheffler K, Hennig J, Seifritz E: Neu- exertions. Spine J 2004, 4:64-75.
ral correlates of antinociception in borderline personality 154. Richardson C, Hodges P, Hides J: Therapeutic exercise for lumbopelvic
disorder. Arch Gen Psychiatry 2006, 63:659-667. stabilisation. A motor control approach for the treatment and prevention of
130. Seminowicz DA, Davis KD: Cortical responses to pain in healthy low back pain Edinburgh: Churchill Livingstone; 2004.
individuals depends on pain catastrophizing. Pain 2006, 155. Leinonen V, Kankaanpää M, Luukkonen M, Hänninen O, Airaksinen O,
120:297-306. Taimela S: Disc herniation-related back pain impairs feed-for-
131. Flor H: The functional organization of the brain in chronic ward control of paraspinal muscles. Spine 2001,
pain. Progress in Brain Research 2000, 129:313-322. 26:16:E367-372.
132. Harris AJ: Cortical origin of pathological pain. Lancet 1999, 156. Radebold A, Cholewicki J, Panjabi MM, Patel TC: Muscle response
354:1464-1466. pattern to sudden trunk loading in healthy individuals and in
133. McCabe CS, Haigh RC, Halligan PW, Blake DR: Simulating sen- patients with chronic low back pain. Spine 2000, 25:947-954.
sory-motor incongruence in healthy volunteers: Implications 157. Radebold A, Cholewicki J, Polzhofer GK, Greene HS: Impaired pos-
for a cortical model of pain. Rheumatology 2005, 44:509-516. tural control of the lumbar spine is associated with delayed
134. Moseley GL, Gandevia SC: Sensory-motor incongruence and muscle response times in patients with chronic idiopathic
reports of 'pain'. Rheumatology 2005, 44:1083-1085. low back pain. Spine 2001, 26:724-730.
135. Moseley GL, McCormick K, Hudson M, Zalucki N: Disrupted cor- 158. Wilder DG, Aleksiev AR, Magnusson ML, Pope MH, Spratt KF, Goel
tical proprioceptive representation evokes symptoms of VK: Muscular response to sudden load: A tool to evaluate
peculiarity, foreignness and swelling, but not pain. Rheumatol- fatigue and rehabilitation. Spine 1996, 21:2628-2639.
ogy 2006, 45:196-200. 159. Luoto S, Aalto H, Taimela S, Hurri H, Pyykko I, Alaranta H: One-
136. Jeannerod M: The mechanism of self-recognition in humans. footed and externally disturbed two-footed postural control
Behav Brain Res 2003, 142:1-15. in patients with chronic low back pain and healthy control
137. Fink GR, Marshall JC, Halligan PW, Frith CD, Driver J, Frackowiak RS, subjects. A controlled study with follow-up. Spine 1998,
Dolan RJ: The neural consequences of conflict between inten- 23:19:2081-9.
tion and the senses. Brain 1999, 122:497-512. 160. Mientjes MIV, Frank JS: Balance in chronic low back pain
138. Adams M, Bogduk N, Burton K, Dolan P: The Biomechanics of Back Pain patients compared to healthy people under various condi-
Edinburgh: Churchill Livingston; 2002. tions in upright standing. Clin Biomech 1999, 14:710-716.
139. Dolan P, Adams MA: Influence of lumbar and hip mobility on 161. Mok NW, Brauer SG, Hodges PW: Hip strategy for balance con-
the bending stresses acting on the lumbar spine. Clin Biomech trol in quiet standing is reduced in people with low back pain.
1993, 8:185-192. Spine 2004, 29:6:E107-112.
140. Keefe FJ, Hill RW: An objective approach to quantifying pain 162. Nies N, Sinnott PL: Variations in balance and body sway in mid-
behavior and gait patterns in low back pain patients. Pain dle-aged adults. Subjects with healthy backs compared with
1985, 21:153-161. subjects with low-back dysfunction. Spine 1991, 16(3):325-30.
141. Lamoth CJ, Meijer OG, Wuisman PI, van Dieën JH, Levin MF, Beek PJ: 163. Brumagne S, Cordo P, Lysens R, Verschueren S, Swinnen S: The role
Pelvis-thorax coordination in the transverse plane during of paraspinal muscle spindles in lumbosacral position sense
walking in persons with nonspecific low back pain. Spine 2002, in individuals with and without low back pain. Spine 2000,
27:4:E92-9. 25:989-994.
142. Larivie're C, Gagnon D, Loisel P: The effect of load on the coor- 164. Gill KP, Callaghan MJ: The measurement of lumbar propriocep-
dination of the trunk for subjects with and without chronic tion in individuals with and without low back pain. Spine 1998,
low back pain during flexion-extension and lateral bending 23:371-377.
tasks. Clin Biomech 2000, 15:407-416. 165. Taimela S, Kankaanpää M, Luoto S: The effect of lumbar fatigue
143. Porter JL, Wilkinson A: Lumbar-hip flexion motion. A compar- on the ability to sense a change in lumbar position: A con-
ative study between asymptomatic and chronic low back trolled study. Spine 1999, 24:1322-1327.
pain in 18- to 36-year-old men. Spine 1997, 22:1508-1514. 166. Luoto S, Taimela S, Hurri H, Aalto H, Pyykkö L, Alaranta H: Psycho-
144. Selles RW, Wagenaar RC, Smit TH, Wuisman PIJM: Disorders in motor speed and postural control in chronic low back pain
trunk rotation during walking in patients with low back pain: patients: A controlled follow-up study. Spine 1996,
A dynamical systems approach. Clin Biomech 2001, 16:175-181. 21:2621-2627.
145. Vogt L, Pfeifer K, Portscher M, Banzer W: Influences of nonspe- 167. Luoto S, Taimela S, Hurri H, Alaranta H: Mechanisms explaining
cific low back pain on three-dimensional lumbar spine kine- the association between low back trouble and deficits in
matics in locomotion. Spine 2001, 26:1910-1919. information processing. A controlled study with follow-up.
146. Marras WS, Parnianpour M, Ferguson SA, Kim JY, Crowell RR, Simon Spine 1999, 24:3:255-61.
SR: Quantification and classification of low back disorders 168. Taimela S, Osterman K, Alaranta H, Soukka A, Kujala UM: Long psy-
based on trunk motion. Eur J Phys Med Rehab 1993, 3:218-235. chomotor reaction time in patients with chronic low-back
147. Marras WS, Parnianpour M, Ferguson SA, Kim JY, Crowell RR, Bose pain: Preliminary report. Arch Phys Med Rehab 1993,
S, Simon SR: The classification of anatomic- and symptom- 74(11):1161-1164.
based low back disorders using motion measure models. 169. Moseley GL, Hodges P: Chronic pain and motor control. In
Spine 1995, 20:2531-2546. Grieves Modern Manual Therapy 3rd edition. Edited by: Boyling JD, Jull
148. Marras WS, Ferguson SA, Gupta P, Bose S, Parnianpour M, Kim JY, GA. Edinburgh: Churchill Livingstone; 2004:215-232.
Crowell RR: The quantification of low back disorder using 170. Barr KP, Griggs M, Cadby T: Lumbar stabilization: Core con-
motion measures: Methodology and validation. Spine 1999, cepts and current literature, part 1. Am J Phys Med Rehab 2005,
24:2091-2100. 84:473-480.
149. Cassisi JE, Robinson ME, O'Conner P, MacMillan M: Trunk strength 171. O'Sullivan PB: Lumbar segmental 'instability': Clinical presen-
and lumbar paraspinal muscle activity during isometric exer- tation and specific stabilizing exercise management. Manual
cise in chronic low-back pain patients and controls. Spine Therapy 2000, 5:2-12.
1993, 18(2):245-251. 172. Ferreira PH, Ferreira ML, Maher CG, Herbert RD, Refshauge K: Spe-
150. Grabiner MD, Koh TJ, El Ghazawi A: Decoupling of bilateral par- cific stabilisation exercise for spinal and pelvic pain: A sys-
aspinal excitation in subjects with low back pain. Spine 1992, tematic review. Aust J Physiother 2006, 52(2):79-88.
17:10:1219-1223. 173. Hayden JA, Van Tulder MW, Malmivaara AV, Koes BW: Meta-anal-
151. Ferguson SA, Marras WS, Burr DL, Davis KG, Gupta P: Differences ysis: Exercise therapy for nonspecific low back pain. Ann Int
in motor recruitment and resulting kinematics between low Med 2005, 142:765-775.
Page 14 of 15
174. Assendelft WJJ, Morton SC, Yu EI, Suttorp MJ, Shekelle PG: Spinal study of transcranial direct current stimulation for the treat-
Manipulative Therapy for Low Back Pain: A Meta-Analysis of ment of pain in fibromyalgia. Arthritis and Rheumatism 2006,
Effectiveness Relative to Other Therapies. Ann Int Med 2003, 54:3988-3998.
138:871-881. 197. Antal A, Nitsche MA, Kruse W, Kincses TZ, Hoffmann K, Paulus W:
175. Pincus T, Burton AK, Vogel S, Field AP: A systematic review of Direct current stimulation over V5 enhances visuomotor
psychological factors as predictors of chronicity/disability in coordination by improving motion perception in humans. J
prospective cohorts of low back pain. Spine 2002, Cog Neurosci 2004, 16:4:521-527.
27:5:E109-120. 198. Kincses TZ, Antal A, Nitsche MA, Bártfai O, Paulus W: Facilitation
176. Pincus T, Vogel S, Burton AK, Santos R, Field AP: Fear avoidance of probabilistic classification learning by transcranial direct
and prognosis in back pain: A systematic review and synthe- current stimulation of the prefrontal cortex in the human.
sis of current evidence. Arthritis Rheum 2006, 54:12:3999-4010. Neuropsychologia 2004, 42:1:113-117.
177. Young-Casey C, Greenberg MA, Nicassio PM, Harpin RE, Hubbard D: 199. Wassermann EM, Grafman J: Recharging cognition with DC
Transition from acute to chronic pain and disability: A model brain polarization. Trends Cog Neurosci 2005, 9:503-505.
including cognitive, affective, and trauma factors. Pain 2008,
134(11–22):69-79.
178. George MS, Ketter TA, Post RM: Prefrontal cortex dysfunction Pre-publication history
in clinical depression. Depression 1994, 2:59-72. The pre-publication history for this paper can be accessed
179. Pascual-Leone A, Rubio B, Pallardo' F, Catala' MD: Rapid-rate tran- here:
scranial magnetic stimulation of left dorsolateral prefrontal
cortex in drug-resistant depression. Lancet 1996, 348:233-237.
180. Fitzgerald PB, Oxley TJ, Laird AR, Kulkarni J, Egan GF, Daskalakis ZJ: http://www.biomedcentral.com/1471-2474/9/11/prepub
An analysis of functional neuroimaging studies of dorsola-
teral prefrontal cortical activity in depression. Psychiatry
Research – Neuroimaging 2006, 148:33-45.
181. Rogers MA, Kasai K, Koji M, Fukuda R, Iwanami A, Nakagome K,
Fukuda M, Kato N: Executive and prefrontal dysfunction in uni-
polar depression: A review of neuropsychological and imag-
ing evidence. Neurosci Res 2004, 50:1-11.
182. Ostelo RW, van Tulder MW, Vlaeyen JW, Linton SJ, Morley SJ, Assen-
delft WJ: Behavioural treatment for chronic low-back pain.
Cochrane database of systematic reviews 2005.
183. Schweikert B, Jacobi E, Seitz R, Cziske R, Ehlert A, Knab J, Leidl R:
Effectiveness and cost-effectiveness of adding a cognitive
behavioural treatment to the rehabilitation of chronic low
back pain. J Rheumatol 2006, 33(12):2519-2526.
184. Vlaeyen JWS, Linton SJ: Fear-avoidance and its consequences in
chronic musculoskeletal pain: A state of the art. Pain 2000,
85:317-332.
185. Leeuw M, Goossens MEJB, Linton SJ, Crombez G, Boersma K,
Vlaeyen JWS: The Fear-Avoidance Model of Musculoskeletal
Pain:Current State of Scientific Evidence. Journal of Behavioral
Medicine 2007, 30:1:77-94.
186. Vlaeyen JWS, Crombez G: Fear of movement/(re)injury, avoid-
ance and pain disability in chronic low back pain patients.
Manual Therapy 1999, 4:187-195.
187. Keefe F, Nicholas M, Vlaeyen J: Psychological Assessment and
Management of Pain. In Pain 2005 – An Updated Review Edited by:
Justins D. IASP Press; 2005.
188. Turk D, Okifuji A, Sherman J: Psychological aspects of back pain:
implications for physical therapists. In Physical Therapy of the Low
Back 3rd edition. Edited by: Twomey LT, Taylor JR. Edinburgh:
Churchill Livingstone; 2000.
189. Main CJ, Spanswick CC: Pain Management: an interdisciplinary approach
Edinbugh: Churchill Livingstone; 2000.
190. Eccleston C, Crombez G: Pain demands attention: A cognitive-
affective model of the interruptive function of pain. Psycholog-
ical Bulletin 1999, 125:3:356-366.
191. Watson PJ: Managing Chronic Pain. In Grieve's Modern Manual
Therapy 3rd edition. Edited by: Boyling JD, Jull GA. Edinburgh: Church-
ill Livingstone; 2004:551-566.
192. Moseley GL, Zalucki NM, Wiech K: Tactile discrimination, but Publish with Bio Med Central and every
not tactile stimulation alone, reduces chronic limb pain. Pain
in press. 2007; Dec 1 scientist can read your work free of charge
193. Ramachandran VS, Rogers-Ramachandran D: Synaesthesia in "BioMed Central will be the most significant development for
Phantom Limbs Induced with Mirrors. Proc Biol Sci 1996, disseminating the results of biomedical researc h in our lifetime."
263:1369:377-386.
194. de Charms RC, Maeda F, Glover GH, Ludlow D, Pauly JM, Soneji D, Sir Paul Nurse, Cancer Research UK
Gabrieli JD, Mackey SC: Control over brain activation and pain Your research papers will be:
learned by using real-time functional MRI. Proc Natl Acad Sci
USA 2005, 102:18626-18631. available free of charge to the entire biomedical community
195. Antal A, Nitsche M, Paulus W: Non-invasive transcranial stimu- peer reviewed and published immediately upon acceptance
lation of the brain in patients with pain. Klinische Neurophysiolo-
gie 2004, 35:241-244. cited in PubMed and archived on PubMed Central
196. Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, yours — you keep the copyright
Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A,
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Background for considerable healthcare and socioeconomic costs [2].

Change in cortical Change in

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