Journal of Bodywork & Movement Therapies (2015) 19, 205e212

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CRITICAL REVIEW

Effectiveness of neural mobilization

in patients with spinal radiculopathy:
A critical review
Michalis A. Efstathiou, MSc a, Manos Stefanakis, PhD a,*,
Christos Savva, MSc b, Giannis Giakas, PhD c

a
Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
b
School of Sciences, European University, Nicosia, Cyprus
c
Department of Physical Education & Sports Science, University of Thessaly, Trikala, Greece

Received 25 March 2014; received in revised form 8 August 2014; accepted 10 August 2014

KEYWORDS Summary Spinal radiculopathy (SR) is a multifactorial nerve root injury that can result in sig-
Neurodynamics; nificant pain, psychological stress and disability. It can occur at any level of the spinal column
Sliders; with the highest percentage in the lumbar spine. Amongst the various interventions that have
Tensioners; been suggested, neural mobilization (NM) has been advocated as an effective treatment op-
Foraminal stenosis; tion. The purpose of this review is to (1) examine pathophysiological aspects of spinal roots
Nerve root and peripheral nerves, (2) analyze the proposed mechanisms of NM as treatment of injured
involvement; nerve tissues and (3) critically review the existing research evidence for the efficacy of NM
Neural Tissue in patients with lumbar or cervical radiculopathy.
Provocation Tests; ª 2014 Elsevier Ltd. All rights reserved.
Radiculopathy;
Radicular pain

Introduction root(s) most commonly caused by a disc herniation, or a

space-occupying lesion that can result in nerve root
Nerve roots are susceptible to injury at any level of the inflammation, impingement, or both (Wainner et al., 2003).
spinal column, with a high percentage of these injuries Also, malignant and infectious causes of SR have been re-
occurring at the lumbar and cervical spine (Konstantinou ported and hence should always be suspected, as these
and Dunn, 2008; Abbed and Coumans, 2007). Spinal radi- patients would require medical referral and not any type of
culopathy (SR) is defined as a disorder of the spinal nerve physiotherapy intervention (Stafford et al., 2007).

* Corresponding author. University of Nicosia, Department of Life and Health Sciences, School of Sciences and Engineering, Physiotherapy
Program Coordinator, Nicosia, Cyprus. Tel.: þ357 22842564; fax: þ357 22842555.
E-mail address: [email protected]
(M. Stefanakis).

http://dx.doi.org/10.1016/j.jbmt.2014.08.006
1360-8592/ª 2014 Elsevier Ltd. All rights reserved.
206 M.A. Efstathiou et al.

Depending on the spinal level of nerve root irritation, SR sciatic nerve of rats produced 50% drop in nerve blood flow
can be further categorized as cervical (CR), thoracic (TR) measured with laser Doppler flowmetry. The effects of
and lumbar radiculopathy (LR). Epidemiological data for CR nerve compression, have also been extensively explored in
has shown an annual incident of 0.1% in males and 0.06% in animal models using various methods (miniature inflatable
females in the general population with an increased prev- cuffs or silicon tubes around the nerve) to induce acute or
alence occurring in the fifth decade of life (Radhakrishnan chronic compression (Dahlin and Kanje, 1992; Dyck et al.,
et al., 1994). In the lumbar spine, the frequency of LR is 1990). Extraneural pressures have been found to inhibit
highly variable, depending largely on the characteristics of intraneural microvascular blood flow, axonal transport and
the population studied, with annual values ranging from nerve function with increases of intrafascicular pressure in
2.2% in the general population to 34% in specific working a doseeresponse manner (Rempel et al., 1999).
populations (Konstantinou and Dunn, 2008). Men are more The main sources of compressive stress that will impede
likely to have LR in their 4th decade of life, while women blood flow of the nerve root are disc herniations, osteo-
have higher rates in their 5th and 6th decade of life (Tarulli phytes of the facet or uncovertebral joints and stenosis of
and Raynor, 2007). Thoracic disc herniation and diabetes the spinal canal (Kobayashi et al., 2003). With the contrary
mellitus are two of the most common etiologies for the to dorsal root ganglion (Bogduk, 2009), root compressions
development of TR. There is no available epidemiological can cause sensory and motor dysfunction but usually not
data on TR, however certain data on thoracic disc hernia- pain (Mulleman et al., 2006). Pain, is typically generated
tions indicate that they occur in only 0.15e4% of all when microvascular alterations as a result of compression
symptomatic disc herniations of the spine, and they lead to upregulation of inflammatory mediators (Kobayashi
represent less than 2% of all spinal disc surgeries (O’Connor et al., 2004). Inflammation can ultimately lead to adhesions
et al., 2002). Since thoracic disc herniations are the less between the herniated disc and the nerve root that will
common across the whole spine and since disc herniation is impair gliding of the nerve root. In the acute and sub-acute
the most common cause of SR (Radhakrishnan et al., 1994), stages of nerve root compression, neural conduction block,
TR should also be less common than CR and LR. intraneural edema, mechanical sensitization and increase
The pattern and location of the patient’s symptoms may of sodium channel density have been reported (Chen et al.,
vary significantly, depending on the level of the affected 2003; Kobayashi et al., 2004; Rempel et al., 1999).
nerve root (Cleland et al., 2005). The two most commonly Dysfunction can also extend to primary sensory neurons
affected levels are L4-5 or L5-S1 (90%) among all LRs within the dorsal root ganglion (Kobayashi et al., 2004). The
(Murphy et al., 2009), and C7 (31%e81%), C6 (19%e25%) and result of these changes manifests itself as increased
C5 (2%e14%) among all CRs (Greathouse and Joshi, 2010). mechanosensitivity. It is worth noting that the critical
For TR, T11-T12 interspace is affected in 26%e50% of all threshold for duration and magnitude of compression has
cases (O’Connor et al., 2002). Common symptoms include not been fully determined yet (Rempel and Diao, 2004).
weakness, numbness, paresthesia or a combination of all Furthermore, substances contained in the herniated
these symptoms (Young et al., 2009), which often cause material can cause inflammation and radicular pain without
disability and functional limitations (Cleland et al., 2005). evidence of true mechanical compression (Videman and
SRs are often accompanied by (radicular) pain, but they are Nurminen, 2004). This is because the nucleus pulposus is
not defined by pain, as they can often occur in the absence a very powerful inflammatory stimulus (Takahashi et al.,
of it (Bogduk, 2009). 2003; Mulleman et al., 2006) possibly due to its high pro-
teoglycan content (Urban and Roberts, 2003). Takebayashi
Pathophysiology of injured nerves et al. (2001), found mechanical hypersensitivity in the
dorsal root ganglion of 14 rats after implanting nucleus
In order to understand the mechanism through which any pulposus at the L5 nerve root. In another animal study,
type of technique can have an effect on neural tissues, it is induced neuritis in the sciatic nerve of rats produced axonal
essential to understand the cascade of events that occur inflammation characterized by recruitment of macrophages
once a nerve has been affected by a mechanical or chem- and lymphocytes (Bove et al., 2003). This led to an increase
ical stimulus that exceeds its threshold of tolerance. of the pro-inflammatory cytokine, tumor necrosis factor
Nerves have the ability to adjust to different types of alpha (TNFa), which in turn created spontaneous activity in
mechanical stress imposed on them due to normal every nociceptors via an increase in sodium channel conductance.
day limb movements (Topp and Boyd, 2006). It is important Elevated levels of neurotrophines such as nerve growth
for the integrity of the nerve that the duration and/or factor can sensitize C fibers of the nervi nervorum resulting
degree of the stress never exceeds the nerve’s ability to in the release of prostaglandins and bradykinin (Onda
withstand it. Ischemia and impaired function seem to be et al., 2005; Greening, 2004). Other inflammatory media-
the first results when intraneural circulation and tors such as serotonin have also been involved (Kato et al.,
axoplasmic flow are blocked by compressive, tensile or 2008). Interestingly, these inflammatory responses can
shear forces (Topp and Boyd, 2006). Animal studies have cause nerve mechanosensitivity without evidence of major
demonstrated that nerves show time-dependent visco- axonal degeneration and damage (Bove, 2008). Dilley et al.
elastic behavior (Topp and Boyd, 2006). Driscoll et al. (2005) found that induced local neuritis in the nerve trunks
(2002) investigated the effect of 16.1% strain on the of adult rats caused small numbers of structurally intact
sciatic nerve of 10 rabbits. They found that 16.1% of strain myelinated and unmyelinated afferent fibers to develop
resulted in nerve blood flow reduction of 78% and that this increased sensitivity to stretch and pressure. Patients pre-
reduction failed to recover after 30 min of rest. Jou et al. senting with radicular-like pain without radiculopathy
(2000) also found that 24% and 32% lengthening of the (sensory and motor disturbance) are sometimes provided
Effectiveness of neural mobilization in patients with spinal radiculopathy 207

with general diagnosis such as “non-specific neck and arm relation to joint range of movement has also been explored
pain” or “cervico-brachial pain syndrome”. Therefore, (Herrington, 2006), as well as the effectiveness of NM in
these diagnostic labels can include both radicular and various types of peripheral neuropathies by means of
referred pain. Given that SRs with inflammation only, improvement in pain (Tal Akabi and Rushton, 2000; Nagrale
without conduction problems closely resemble this clinical et al., 2012; Coppieters et al., 2003b) and motor nerve
picture, studies that use these terms will also be reviewed. conduction velocity (Ha et al., 2012).
Apparently, a mixture of compressive and inflammatory McKeon and Yancosek (2008) conducted a systematic
processes has a synergistic effect. There is evidence review to assess the effectiveness of NM techniques for the
showing that, nerve injury is more pronounced when treatment of carpal tunnel syndrome. NM showed only a
compression and chemical irritation present in combination positive trend towards improvement. In another systematic
than when each factor acts alone (Takahashi et al., 2003; review, (Ellis and Hing, 2008), the therapeutic efficacy of
Onda et al., 2005). Finally, as in any clinical pain state, NM in various musculoskeletal disorders such as low back
insult to peripheral nerves will result in central sensitiza- pain, carpal tunnel syndrome, cervicobrachial neurogenic
tion with varying degree of severity (Woolf, 2011). In pain and lateral epicondylalgia was examined. Ten RCTs
addition, it has been shown that nerve root irritation pro- were included and the majority of these showed significant
duces a stronger central response than peripheral nerve benefit after the application of NM techniques. Nonethe-
irritation (Greening, 2004). less, the authors in both reviews concluded that evidence
for the efficacy of NM must be considered as limited due to
Treatment methodological quality of the trials. They suggest that
future studies should use more homogenous study designs,
All three SR have a good prognosis and non-operative populations and pathologies.
treatment is the appropriate initial approach (Kuijper
et al., 2009; Stafford et al., 2007). Various interventions Mechanisms of neural mobilization
(manual therapy, traction, exercise and electrotherapy)
have been proposed for cervical and lumbar radiculopathy Although several cadaveric, animal and in-vivo studies have
and have been further scrutinized in systematic reviews been conducted in order to decipher the plausible mecha-
(Clarke et al., 2010; Hahne et al., 2010; Boyles et al., nisms underlining the effectiveness of NM, the proposed
2011). However, there is still a need for additional high explanations remain largely theoretical.
quality trials that will allow firmer conclusions on the In a recent study by Brown et al. (2011), researchers
effectiveness of these interventions (Hahne et al., 2010). examined whether the application of NMs on the tibial
nerve in cadavers could have any effect on the simulated
Neural mobilization (NM) intraneural edema of the nerve. The results showed that
passive NM induced a significant increase in fluid dispersion
Different techniques that aim to mobilize the peripheral of the tibial nerve and could thus possibly explain how
nervous tissue or its surrounding structures have gained these techniques can prevent or reduce intraneural edema.
considerable attention among therapists and researchers Similar results are expected to be seen in living humans
collectively known as NMs. These techniques are used by with peripheral nerve or root involvement although this
therapist for assessment and treatment of various should be evaluated in future studies (Brown et al., 2011).
compression syndromes as well as other conditions that The ability of NMs to induce hypoalgesia has been
may or may not involve neuropathic pain such as lateral investigated. Beneciuk et al. (2009), found that a specific
epicondylalgia (Vicenzino, 2003). They involve a specific tensioning technique performed on the median nerve had
sequence of joint movements in which the therapist an immediate hypoalgesic effect on C-fiber mediated pain,
lengthens the nerve at one joint and simultaneously re- shown by thermal quantitative sensory testing on asymp-
duces its length at an adjacent joint in order to produce tomatic subjects. The authors suggested that the mecha-
sliding movements of neural structures relative to adjacent nism by which NM decreases thermal pain could be
tissues. These are known as sliders or gliding techniques inhibition at the dorsal horn (Beneciuk et al., 2009). These
(Shacklock, 2005; Butler, 2000). A slightly more aggressive positive results although informative are only short term
maneuver is a tensioning technique which increases the and need to be validated with double-blind RCTs in symp-
distance between each end of the nerve tract in an oscil- tomatic population.
latory fashion (Shacklock, 2005; Butler, 2000). In addition, In an animal study (Santos et al., 2012) researchers
other techniques that produce an opening action around explored the effect of NM on chronic constriction model of
the nerve root such as dynamic and static opening of the sciatic nerve injury in 10 male rats. Immunohistochemistry
bony and fascial interface (e.g. lateral glides) (Shacklock, and special protein analysis tests were used in order to
2005; Elvey, 1986) have been proposed for reduction of measure nerve growth factor (NGF) and glia fibrillary acid
nerve root mechanosensitivity. Advocators of NM suggest proteins (GFAP) in the dorsal root ganglion and spinal cord
that these techniques can be utilized to potentially reha- of the animals. This was supplemented with assessment of
bilitate normal function of the nervous system (Nee and allodynia and thermal and mechanical hyperalgesia. With
Butler, 2006). So far, it has been shown that these tech- the completion of 10 treatment sessions, researchers found
niques produce different amounts of longitudinal nerve a decrease of NGF and GFAP in the dorsal root ganglion and
excursion and strain, in both in vivo (Coppieters et al., decrease of GFAP in the lumbar spinal cord along with
2009) and cadaver studies (Coppieters and Butler, 2008; associated reduction of allodynia and hyperalgesia in the
Coppieters et al., 2006). Assessment of nerve mobility in experimental group. Although the results should be
208 M.A. Efstathiou et al.

interpreted with caution, findings from this study provide the specific site of nerve injury, but suggests increased
preliminary evidence that NMs can have an effect on in- mechanical sensitivity. Based on this, it is difficult to
flammatory mediators involved in nerve pain. determine whether symptoms were due to nerve root irri-
In another animal study (Bertolini et al., 2009), re- tation or any other dysfunction along the nerve tract.
searchers divided 23 rats with experimentally induced In another pilot study (Allison et al., 2002), the authors
sciatica in three groups, receiving either dynamic or, static randomly allocated 30 patients with cervico-brachial pain
stretch of the sciatic nerve or sham treatment for 5 sessions. syndrome in three groups to receive either manual therapy
Pain was assessed with the use of a functional incapacitation with a focus on articular tissues of the shoulder and
test that measures paw elevation time during gate. Rats in thoracic spine, NM techniques (lateral glides) or no treat-
the NM group showed lower paw elevation time and there- ment. Pain scores showed significantly lower values in the
fore greater reduction in pain compared to the static stretch NM group compared to the other two groups. Similarly to
and the sham group. Authors explained their findings in the previous study, the term “cervico-brachial pain syn-
terms of reduced edema and intraneural adhesions which drome” is a rather general term that can include other
result in restoration of nerve mechanosensitivity. peripheral nerve lesions apart from those of nerve roots.
Coppieters et al. (2003a) conducted a randomized clin-
ical trial and divided 20 patients with peripheral neurogenic
Neural mobilization in cervical radiculopathy cervicobrachial pain in two groups to receive either NMs
(lateral glides) or ultrasound. Inclusion criteria were based
In a prospected observational cohort study (Murphy et al., on certain clinical tests formulated by Elvey (1997) and
2006), a multi-faceted treatment approach was applied in included techniques of active and passive moment analysis,
27 patients with CR. Treatment was tailored to each patient peripheral-nerve provocation tests and nerve palpation.
and only those techniques that were deemed appropriate Patients treated with NMs had significant changes for all
after thorough assessment were used on each patient. outcome measures (ROM for elbow extension, symptom
Modalities used in this study were cervical manipulation, distribution, and pain intensity) immediately after the
over the door traction, end range loading maneuvers and intervention compared to patients treated with ultrasound.
NM directed to the affected nerve root. In the 3 months Although there was no follow up in order to evaluate any
follow up, 25/27 patients reported clinically significant sustained long term effects for NM, results indicate that NM
improvement in pain and disability. Despite the positive has an immediate short term positive effect compared to
results, this study design does not allow any constructive ultrasound for patients with this type of neurogenic pain.
conclusion on the effectiveness of NMs in isolation. In one case study (Savva and Giakas, 2013), a slider NM
Ragonese (2009), carried out a randomized trial technique was simultaneously applied on the median nerve
comparing manual therapy (cervical lateral glides, nerve with cervical traction, on a patient with CR. The patient
glides, thoracic mobilizations) against therapeutic exercise reported improvement in all outcome measures including
(deep neck flexor, trapezius and serratus anterior pain, and functional activities after 12 sessions spread over
strengthening) or a combination of both in 30 patients with a period of one month. Although case studies can only
CR. Inclusion criteria for CR was based on 4 examination inform evidence based practice to a limited extend, it is
findings (positive Spurling test, positive upper limb tension worth pointing out that this was the first study that used
test, positive distraction test and ipsilateral cervical rota- these two techniques (NM and traction) simultaneously.
tion less than 60 ). The group which received the combi- The rationale was that the cervical nerve root needs to be
nation of exercise and manual therapy demonstrated the decompressed before mobilization is applied. Of course,
greatest improvements in terms of pain and disability after larger, high quality randomized controlled trials must be
9 treatment sessions in 3 weeks. Although the researcher conducted in order to validate the effectiveness of these
used a small sample size of patients with CR, results two techniques combined.
demonstrate an additive effect on pain when NMs com- Collectively, current evidence for the efficacy of NM
plement therapeutic exercises. techniques for patients with CR seems to be limited as only
A recent randomized controlled trial, conducted by Nee 3 studies have explored these techniques in patients with
et al. (2012) used 60 patients with nerve related neck and CR (Murphy et al., 2006; Ragonese, 2009; Savva and Giakas,
arm pain who were randomized in two groups receiving 2013) and 3 studies in patients with nerve related neck and
either NMs (lateral glides, nerve glides) with manual ther- arm pain (Nee et al., 2012; Allison et al 2002; Coppieters
apy and education or advice to remain active alone. Par- et al., 2003a). NM techniques used in these studies mainly
ticipants were excluded if they presented with two or more include treatment protocols as described by Elvey (1986).
abnormal neurological findings at the same nerve root level These follow the general principle of mobilizing tissues
or were suspected to have myelopathy or other red flags. surrounding the nerve roots (nerve bed) in the acute phase
Patients in the experimental group showed immediate, followed by techniques directed at the neural tissue itself
clinically relevant benefits after only 4 treatment sessions as mechanosensitivity decreases.
without any adverse effects related to the application of
NM. This was the first randomized controlled trial that used
a between group analysis in order to assess the effective- Neural mobilization in lumbar radiculopathy
ness of NM in the short term. It is worth mentioning, that
the inclusion criteria for this study population was based on Murphy et al. (2009), undertook an observational cohort
a positive response to the application of upper limb neu- study which applied a multimodal treatment approach,
rodynamic test 1. This test does not inform the clinician of using a management algorithm depending on the patient’s
Effectiveness of neural mobilization in patients with spinal radiculopathy 209

symptoms. All 49 patients with LR were treated with a perineurium in nerve roots (Sunderland, 1990) is difficult to
combination of manipulation, myofascial therapy and NM discern.
depending on the source of their symptoms on an individual In addition, one randomized clinical trial (Nagrale et al.,
basis. Each patient was seen 2e3 times per week for 3 2012), one pilot clinical trial (Cleland et al., 2006), one
weeks initially, after which they were reassessed. This was case series study (George, 2002) and two case studies
followed by either continued frequency of 2 times per week (George, 2000; Cleland et al., 2004), also reported favor-
or a reduction in frequency to 1 time per week. The mean able changes in symptoms. Oddly enough though, all five
number of treatments was 12.6, with a mean duration of studies excluded patients with LR assuming that partici-
follow up after the end of treatment of 14.5 months. pants who lacked nerve root involvement had a less severe
Approximately, 90% of patients reported an “excellent” or condition and thus were more likely to respond to NM.
“good” outcome and more than 70% of patients had a
clinically meaningful improvement in disability. In addition,
74% of patients reported meaningful improvement in pain Discussion
and these improvements were maintained 14.5 months
after the end of the treatment. NM techniques were Viewed in concert, results from available studies point to-
applied in all participants in an attempt to minimize ad- ward a trend favoring NM techniques for SR but remain far
hesions in the involved nerve root. The study was con- from conclusive. Up to this point there are several reasons
ducted in a single practice setting with a relatively small why we cannot reach any definite conclusions on the
sample size, and without a control group. In addition, effectiveness of NM on patients with SRs:
during the 14.5 months follow up, natural history could be
credited for some of the improvement. Nevertheless, its 1) Existing research literature lacks well designed RCTs
findings are promising despite the fact that the beneficial that could clarify the effect of NM in SRs. Available
results cannot be attributed to NM alone. clinical trials and case studies have small sample sizes,
In contrast to the previous study, Scrimshaw and Maher while most of them use a multimodal treatment
(2001) randomly allocated 81 patients with LR that had approach that deprives us conclusive evidence of NM
undergone spinal surgery (lumbar discectomy, fusion or effectiveness in isolation.
laminectomy) into two groups, one receiving standard 2) Heterogeneity among studies seems to be a reason why
postoperative care and the other group standard post- it is so difficult to identify which treatment is most likely
operative care plus NM. The results after 12 months of to be beneficial in which patient group. Chaitow et al.
follow up indicated that NM did not offer any additional (2004) stress that if clinical trials wrongly assume that
benefit to standard care alone. Nevertheless, it is impor- a large patient population is homogenous, they would
tant to underline that Patients demonstrated normal fail to show clinical efficacy for specific interventions
straight leg raise test. NM could have been more effective favorable for a certain smaller sub-group. A stratified
for these patients if their SLR, indicated increased neural approach by use of prognostic screening has been shown
mechanosensitivity. In addition, this study is the only one in to be more effective than non-classification manage-
post-surgical population, and the effects of surgical trauma ment (Flynn et al., 2002; Hill et al., 2011). Classification
in central nervous system mechanosensitivity makes inter- systems like the one proposed by Schafer et al. (2009)
pretation of the results more complicated. are on the right track for identifying which patient
Schafer et al. (2011), carried out a prospective cohort sub-group is more likely to respond to NM.
study in an attempt to explore whether pain and disability 3) Definitions used across studies in order to describe pa-
differ in sub-groups of low back and leg pain treated with thology are non-specific and can include a range of
NM. The researchers proposed a pathomechanism-based different neurogenic and somatic disorders. For the
system of evaluation which consisted of four categories: medical community and pain scientists who are familiar
(1) patients with neuropathic sensitization, (2) patients with terms like radiculopathy and radicular pain, label-
with denervation, (3) patients with peripheral nerve ing such as “cervico-brachial pain syndrome”, “non-
sensitization and (4) patients with musculoskeletal pain. radicular low back pain” or “non-specific neck and arm
NM was utilized on 77 patients divided into one of these pain” is misleading and can create confusion. Sub-
four groups following a standardized assessment protocol. grouping patients in a distinct diagnostic group accord-
After seven treatments with NM techniques, twice per ing to the unique mechanism/cause of their nerve injury
week, the authors found that a significantly greater pro- (aetiological sub-grouping) (Wand and O’Connell, 2008;
portion of patients (56%) in the peripheral nerve sensitiza- Schafer et al., 2009) could help reduce definition
tion group had a positive response to NM compared to the heterogeneity.
other three groups. According to the authors, LR would be
included in the denervation group that did not show a From the evidence presented, radicular pain in SRs
favorable outcome after treatment with NM. The authors seems to emerge from a complex interaction of inflamma-
argued that NM is not the technique of choice for LR, since tory, immune, compression and central processes. For
an NM technique would further stress an already com- instance, proteoglycans from disc nucleus have been shown
pressed, hypoxic and oedematous nerve root and thus to provoke inflammation when they come in contact with
aggravate patient’s symptoms. However, they do not nerve roots (Lee et al., 2006; Kawakami et al., 1999;
comment on the positive effect of NM on peripheral nerves Kayama et al., 1996). NO which is considered responsible
that can also be compressed, hypoxic and oedematous. for mediating this inflammatory response (Brisby et al.,
Whether this difference can be explained by the lack of 2000) is also believed to activate glial cells in the area of
210 M.A. Efstathiou et al.

spinal cord and DRG in cases of neuronal damage (Watkins central mechanisms of pain should always be taken into
and Maier, 2005). Activated astrocytes and other glial consideration and carefully assessed, since both central
cells contribute significantly in cytokine production and and peripheral mechanisms interact (Nijs et al., 2010). It is
sensitization of pain transmitting cells in the dorsal horn of reasonable to postulate that SR patients with dominant,
the spinal cord (Watkins and Maier, 2005; Tsuda et al., hard-to-treat central sensitization that includes maladap-
2005). Prolonged pain due to inflammation as well as the tive psychological factors such as negative emotions
synergistic action of glial derived growth factors and cyto- (depression, anxiety), cognitions (catastrophizing, external
kines, cause memory type changes (long term potentiation) locus of control) and pain behaviors (fear of movement,
in the synapses of the spinal cord, thalamus and the brain fear of reinjury, avoidance of activity) (Zusman, 2002;
collectively called central sensitization (Costigan and Woolf, 2011), would not be appropriate candidates for
Woolf, 2000; Ji et al., 2003). When deciding to implement NMs that essentially target peripheral pain mechanisms
NM as an intervention, meticulous evaluation should be (Schafer et al., 2011). Such maladaptive emotions, cogni-
performed for signs of abnormal CNS sensitivity (e.g tions and behaviors can be screened via a combination of
hyperalgesia, allodynia) as the response to mechanical questionnaires such as Tampa Scale of Kinesiophobia,
treatments such as NM is expected to be limited. McGill Pain Questionnaire, Beck Depression Inventory and
With regards to compression related SRs, an important others (Lebovits, 2000). In those cases a more hands off,
factor to consider is the duration of the compression. Sus- pain management and cognitive-behavioral approach is
tained mechanical compression may in the long term cause recommended by the authors even in the presence of
injury to neurons of the dorsal root ganglion (Kobayashi physical trauma.
et al., 2004), and damage to nerve axons, changes that In conclusion, since there has been considerable evidence
are considered irreversible and thus unlikely to respond to from animal models showing that nerve root inflammation
NM treatment. Also, when presented with periradicular can be present with functional (e.g. mechanosensitivity) but
fibrosis and scarring, the nerve root will be fixed in one not structural nerve root deficits, it should be of interest if
position and thereby applying mechanical force via any kind future studies can ascertain whether these basic science
of neural movement based technique will only increase the findings could then be incorporated into clinical practice.
susceptibility of the nerve root to reinjury (Kobayashi This would allow adequate screening and classification to
et al., 2009, 2003). In this clinical scenario, interventions take place, in order to determine the efficacy of NM on this
that aim at reducing compressive pressure of the nerve root discrete sub-group of patients. With these improvements in
such as traction (Umar et al., 2012; Joghataei et al., 2004), future studies and the integration of basic and clinical
foramina opening techniques (Shacklock, 2005) or lateral research related to NM, there will be immense progress in
glides (Coppieters et al., 2003a) would appear to be more clinical decision-making and management of SRs.
reasonable.
Patients with nerve sensitization due to inflammation in
the absence of detectable nerve damage have been References
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respond to NM treatment. Examination procedures for Abbed, M.K., Coumans, E.C.V.J., 2007. Cervical radiculopathy:
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identifying these patients have been proposed (Nee and
surgery 60, 28e34.
Butler, 2006; Hall and Elvey, 2004) and include neural tis- Allison, T.G., Nagy, M.B., Hall, T., 2002. A randomized clinical trial
sue provocation tests, palpation of nerve trunks and clues of manual therapy for cervico-brachial pain syndrome - a pilot
from specific pain provoking postures or activities. Overall, study. Man. Ther. 7, 95e102.
sensitivity, specificity and validity of this examination Beneciuk, M.J., Bishop, D.M., George, Z.S., 2009. Effects of upper
scheme has yet to be established, although studies have extremity neural mobilization on thermal pain sensitivity: a
shown good inter-rater and intra-rater reliability for certain sham-controlled study in asymptomatic participants. J. Orthop.
neural tissue provocation tests (Vanti et al., 2010; Jespen Sports Phys. Ther. 39, 428e438.
et al., 2006) and promising results from a proposed classi- Bertolini, F.R.G., Silva, S.T., Trindade, L.D., et al., 2009. Neural
fication system (Schafer et al., 2009). Patients more likely mobilization and static stretching in an experimental sciatic
model e an experimental study. Braz. J. Phys. Ther. 13, 493e498.
to respond to NMs are those who demonstrate improvement
Bogduk, N., 2009. On the definition and physiology of back pain,
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