Low‐Level Laser Therapy for Acute Neck Pain with Radiculopathy: A Double‐Blind Placebo‐Controlled Randomized Study

Abstract

The objective of the study was to investigate clinical effects of low-level laser therapy (LLLT) in patients with acute neck pain with radiculopathy.
Double-blind, randomized, placebo-controlled study.
The study was carried out between January 2005 and September 2007 at the Clinic for Rehabilitation at the Medical School, University of Belgrade, Serbia.
Sixty subjects received a course of 15 treatments over 3 weeks with active or an inactivated laser as a placebo procedure. LLLT was applied to the skin projection at the anatomical site of the spinal segment involved with the following parameters: wavelength 905 nm, frequency 5,000 Hz, power density of 12 mW/cm(2), and dose of 2 J/cm(2), treatment time 120 seconds, at whole doses 12 J/cm(2).
The primary outcome measure was pain intensity as measured by a visual analog scale. Secondary outcome measures were neck movement, neck disability index, and quality of life. Measurements were taken before treatment and at the end of the 3-week treatment period.
Statistically significant differences between groups were found for intensity of arm pain (P = 0.003, with high effect size d = 0.92) and for neck extension (P = 0.003 with high effect size d = 0.94).
LLLT gave more effective short-term relief of arm pain and increased range of neck extension in patients with acute neck pain with radiculopathy in comparison to the placebo procedure.

Full text

Low-Level Laser Therapy for Acute Neck Pain
with Radiculopathy: A Double-Blind
Placebo-Controlled Randomized Studypme_9071169..1178
Ljubica M. Konstantinovic, MD, PhD,*
Milisav R. Cutovic, MD, PhD,*
Aleksandar N. Milovanovic, MD, PhD,†
Stevan J. Jovic, MD, PhD,* Aleksandra S. Dragin,
MS,* Milica Dj. Letic, MS,‡and Vera M. Miler, MS§
*Clinic for Rehabilitation,
†Institute for Occupational Medicine and
‡Institute for Rehabilitation, Medical School, University
of Belgrade, Belgrade, Serbia;
§High School dr Djordje Natosevic, Indjija, Serbia
Reprint requests to: Ljubica M. Konstantinovic, MD,
PhD, Clinic for Rehabilitation dr Miroslav Zotovic,
Medical School, University of Belgrade, Sokobanjska
13, Belgrade, Serbia. Tel: +3812602541; Fax:
+381112667623; E-mail: ljkonstantinovic@yahoo.com.
Abstract
Objective. The objective of the study was to inves-
tigate clinical effects of low-level laser therapy
(LLLT) in patients with acute neck pain with
radiculopathy.
Design. Double-blind, randomized, placebo-
controlled study.
Setting. The study was carried out between January
2005 and September 2007 at the Clinic for Rehabili-
tation at the Medical School, University of Belgrade,
Serbia.
Patients and Intervention. Sixty subjects received a
course of 15 treatments over 3 weeks with active or
an inactivated laser as a placebo procedure. LLLT
was applied to the skin projection at the anatomical
site of the spinal segment involved with the follow-
ing parameters: wavelength 905 nm, frequency
5,000 Hz, power density of 12 mW/cm2, and dose of
2 J/cm2, treatment time 120 seconds, at whole doses
12 J/cm2.
Outcome measures. The primary outcome measure
was pain intensity as measured by a visual analog
scale. Secondary outcome measures were neck
movement, neck disability index, and quality of life.
Measurements were taken before treatment and at
the end of the 3-week treatment period.
Results. Statistically significant differences
between groups were found for intensity of arm pain
(P=0.003, with high effect size d =0.92) and for
neck extension (P=0.003 with high effect size
d=0.94).
Conclusion. LLLT gave more effective short-term
relief of arm pain and increased range of neck exten-
sion in patients with acute neck pain with radicul-
opathy in comparison to the placebo procedure.
Key Words. Low-Level Laser Therapy (LLLT); Acute
Neck Pain
Introduction
Acute neck pain with cervical radiculopathy is a common
condition with a reported annual incidence of approxi-
mately 83 per 100,000 and an increased prevalence in
the fifth decade of life (203 per 100,000) [1,2]. The most
common causes of compression of the cervical level nerve
root are stenosis of the lateral canal secondary to spondy-
larthrosis [3] and a prolapsed intervertebral disk (PID) [1].
However, nerve root pain can occur in the absence of
visible compression [4,5]. The main clinical features of the
condition are pain and functional disability, which have a
considerable impact on overall health [6]. Clinical diagno-
sis of cervical radiculopathy is hindered by a lack of
well-defined clinical criteria [7–9]. The scientific evidence
supports the use of manual provocative tests in patients
with neck pain and suspected radiculopathy and together
with a combination of patient history, physical examina-
tion, imaging techniques, and needle electromyography
(EMG) to diagnose the cause and site of cervical radicul-
opathy. Patient self-reported assessment is useful to
evaluate perceived pain, function, disability, and psycho-
social status [10]. The natural course of spondylotic and
discogenic cervical radiculopathy is generally favorable;
however, the percentage of spontaneous recovery is
unknown [11,12]. Several intervention strategies are com-
monly used in the management of cervical radiculopathy.
These range from conservative approaches to surgical
intervention [13]. Conservative treatments have shown
positive results in patients with severe pain and neurolo-
gical lesions [14]. However, it was found that a lower
Pain Medicine 2010; 11: 1169–1178
Wiley Periodicals, Inc.
1169

percentage of patients underwent conservative treatment
as compared to surgery [15], in spite of the fact that no
advantage of surgery has been demonstrated [16]. For
many of the treatment modalities that are used widely in
practice, insufficient evidence supports their use [17,18].
Increasing evidence suggests that inflammation alone or in
association with root compression is the main pathological
factor that is responsible for radiculopathy that is associ-
ated with disk herniation [19]. Disk herniation may cause
pain by mechanical compression of the nerve root. Cervical
nerve roots can also be at risk of injury due to foraminal
impingement and mechanical compression, which lead to
endoneurial edema, neuronal damage, and decreased
axonal conduction velocity, and these in turn are strongly
related to pain [20,21]. Data strongly support the role of
proinflammatory cytokines in pain that is associated with
herniated disks. Cytokines, such as interleukin 3 (IL-3),
IL-6, and IL-8, cause hyperalgesia in animals [22] and
may play a role in the physiopathology of radiculopathy. The
interactions of axons with proinflammatory cytokines could
increase electrical conductivity. Recently, a study demon-
strated the effect of cyclic mechanical stress on the pro-
duction of inflammatory agents and postulated a possible
synergistic effect of simultaneous mechanical and chemi-
cal irritation of the annulus fibrosus cells on the production
of pain mediators, such as prostaglandin E2 [23].
Many experimental and clinical studies have shown anal-
gesic and anti-inflammatory potential of low-level laser
therapy (LLLT) in a dose-dependent manner [24,25]. It has
been shown to be a low risk and safe treatment, but its
true efficacy is controversial. LLLT was demonstrated to
modulate the inflammatory, proliferative, and remodeling
phases of the healing process [26,27]. Important addi-
tional effects appear to include a direct influence on neural
structures that are damaged by compression or inflam-
mation, and this significantly improves nerve recovery
[28–30].
The aim of this study was to investigate the clinical effects
of LLLT in patients with acute neck pain with radiculopa-
thy. We hypothesize that LLLT would provide a clinically
and statistically significant benefit over a placebo for
patients with acute neck pain with radiculopathy.
Materials and Methods
Patients
The study was carried out between January 2005 and
September 2007 at the Clinic for Rehabilitation at the
Medical School, University of Belgrade, Serbia. During this
period, 285 patients with acute neck pain with radiating
arm pain were admitted to the clinic. The prospective
double-blind randomized study included 60 patients with
acute neck pain with unilateral radiculopathy (Figure 1).
Clinical characteristics for inclusion in the study were: neck
and/or unilateral arm pain; clinical signs of radicular lesion
in a dermatomal distribution and/or myotomal muscle
weakness (graded less than 4/5) and/or diminished
reflexes in the upper extremities; disability evaluated as
moderate to severe; absence of symptoms and signs of
myelopathy; duration of symptoms less than 4 weeks;
absence of symptoms or signs of other similar neck and
arm diseases; no more than three previous episodes [31];
and evidence from magnetic resonance imaging (MRI) of a
PID or spondylotic degenerative changes. In the study, 225
patients were not included because they failed to meet
inclusion criteria, were unresponsive to initial contact, or
had red flag symptoms [32], such as neck trauma, diabe-
tes mellitus, inflammatory arthritis, neurological disease, or
cancer disease. In addition, pregnant patients and patients
that had been treated surgically for the same problem or
treated with oral corticosteroids and steroid injections for
any reason in the previous month were not included [33].
Diagnosis was made by a combination of clinical muscu-
loskeletal and neurological examinations of the neck and
upper extremities [34]; provocative tests: upper limb
tension test and Spurling’s test [35]; and additional neu-
roradiological and neurophysiological examinations. MRI
was done before the treatment and was a requirement for
inclusion the trial. Conventional needle myography (EMG)
was performed after 3 to 4 weeks from the beginning of
symptoms; only observations of signs of acute denerva-
tion were considered to be consistent findings, but the
observation of acute denervation was not required for
inclusion in the study.
During the study, two patients dropped out; one due to
nausea and the other due to an increase in blood pres-
sure. However, the last recorded parameters for these
patients were included in the analysis. Withdrawal of the
subjects was not registered.
All patients gave informed written consent to participate
in the study. The study was approved by the Ethics
Committee of the Clinic for Rehabilitation at the Medical
School, University of Belgrade.
Blinding
The patients were allocated randomly into two groups
using 60 sequentially numbered, opaque, sealed enve-
lopes that had been prepared earlier, using a computer-
ized table of random numbers and balanced to ensure
equal numbers in each group. The allocations were con-
cealed from the statistician (GH) until the statistical analy-
sis had been completed.
Treatment
The patients were allocated randomly to one of two treat-
ment groups: Group A (n =30) was treated with local
active LLLT and group B (n =30) was treated with local
placebo LLLT. Laser units were manufactured by Enraf
Nonius. The devices for LLLT were assigned as device A
for active LLLT and device B for placebo LLLT. The
patients did not know which unit was active. Patients were
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treated five times weekly for a total of 15 treatments. All
patients were instructed to perform restricted and allowed
activity (low aerobic activity). Both treatments were applied
by the same therapist, who was also unaware which unit
was active.
Active LLLT Treatment
The parameters of the laser beams are shown in Table 1.
The parameters were chosen on the basis of preliminary
results and previous studies [18,19]. The optical output
was tested before and after the end of the trial.
Placebo LLLT Treatment
Placebo LLLT was applied in the same manner, but using
a unit that had been deactivated by a member of the
Institute for Physics, Belgrade. The physicians and the
patients were unable to distinguish between the active
and placebo units.
Figure 1 Flowchart of patients
recruitment. LLLT =low-level
laser therapy.
285 assessed for eligibility
225 excluded
Reasons:
Not meeting inclusion criteria
(n=95)
Refused to participate (n=30)
Meeting excluding criteria (n=105)
Intention to treat analysis (n=30)
Lost to follow-up (n=0)
Discontinued intervention (n= 2)
Drop out (n=2)
Allocated to active LLLT group (A)
(n=30)
Received allocated intervention
(n=30)
Lost to follow-up (n=0)
Discontinued intervention (n=0)
Drop out (n=0)
Allocated to placebo LLLT group (B)
(n= 30)
Received allocated intervention
(n= 30)
Intention to treat analysis (n=30)
60 randomized
Table 1 Characteristics of the laser beams
Parameters Value used
Wavelength 905 nm (red)
Laser frequency 5,000 Hz
Maximum power output 25 mW
Diode surface 1 cm2
Power density 12 mW/cm2
Energy 2 J/point
Energy density 2 J/cm2at each point
Treatment time 120 seconds at each point
Number of points 6
Daily energy delivered 12 J
Total energy delivered 180 J
Application mode Probe held stationary in
contact with skin
Anatomical site Local transforaminal*
* 2.5 cm and 3.5 cm laterally from process spinosus of
involved (C6, C7, or C8) and the two next distal spinal segment.
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Low-Level Laser Therapy for Acute Neck Pain

Outcomes
The primary outcome measure was intensity of pain.
The secondary outcome measures were: neck mobility,
neck disability index (NDI), and a 12-item short-form
health survey (SF-12). Intensity of pain was measured
using a visual analog scale (VAS), either for neck (VAS-
neck) or for arm (VAS-arm) pain. The VAS corresponded
to a 100-mm horizontal scale, that was graded from
zero, which represented no pain, to 100, which repre-
sented the worst imaginable pain [36,37]. We classified
the changes in VAS scores into bands and analyzed the
resulting data as an ordinal response. Severity of pain
was graded into four groups according to the range
of VAS scores: none to mild (0–30 mm); moderate
(30–60 mm); moderately severe (60–80 mm); and severe
(80–100 mm) [38]. Neck mobility was measured by
assessment of flexion and extension. Flexion was
expressed as the distance in millimeters from the mid-
point of the chin to the apex of the sternal manubrium.
Extension range was evaluated as the distance in milli-
meters from the occipital tuberosities to the spinous
process of C7. NDI consists of a 10-item questionnaire
that assesses the impact of pain on daily activities using
a score from 0 to 5 for each section, with higher values
indicating more severe impact [39]. NDI was represented
as percentage disability, which was calculated from the
measured values (measured sum/50 ¥100). The SF-12
consists of 12 questions that concern general health and
can be divided into two aggregate summary measures:
the physical component summary (PCS) and the mental
component summary [40].
Subjects were evaluated before and at 3 weeks after by
independent physicians, who performed the diagnostic
assessment and were blind to the type of treatment.
To identify any adverse effects of treatment in a
systematic manner, subjects were asked to record any
new symptoms.
Statistics
The analysis was conducted on an “intention to treat”
basis. SPSS 11.5 (SPSS Inc., Chicago, IL) was used
for analysis. The results were expressed as the
mean ⫾standard deviation (SD) for data that had a
normal distribution, or as median (25% and 75% percen-
tiles) for data that were not distributed normally. We
present two types of comparison: 1) comparison of means
obtained prior to therapy and at the end of therapy for
each measured outcome in both groups; and 2) compari-
son between groups of differences in scores obtained
prior therapy and at the end of therapy for each measured
outcome. For (1), statistically significant differences were
tested using both the paired t-test and the Wilcoxon
signed-ranks test for paired observations. For (2), statisti-
cally significant differences were tested using the inde-
pendent t-test or Wilcoxon–Mann–Whitney test for two
independent groups or the chi-square test, depending on
type of outcome variable. The level of statistical signifi-
cance was set at a two-tailed alpha level of 0.05. Post hoc
power analysis was used to analyze the effect size in order
to evaluate the importance of measured changes. An
ordinal regression analysis was performed for changes in
pain severity.
Results
Baseline characteristics are presented in Table 2. Inter-
group baseline statistics were determined with respect
to sex by the chi-square test and t-test and with respect
to age and duration by the independent sample
t-test. A statistically significant difference between the
groups was only verified for duration of symptoms
(t=–2.016, P=0.048); however, this was without clinical
significance in relation to duration of the acute phase.
Most of the other characteristics were evaluated as out-
comes, and some of those presented are only descriptive.
In Table 3, the mean values ⫾SD for outcomes are pre-
sented, except for the PCS before therapy and after
Table 2 Baseline characteristics
Characteristics
Group A
(n =30)
Group B
(n =30)
Age 41.71 ⫾8.63 38.55 ⫾7.86
Male 43.33 40.63
Female 56.67 59.3
Duration of symptoms
(days)
17.27 ⫾4.04 19.13 ⫾3.14
Pain in arm and neck 16/30 18/30
Pain in arm 28/30 27/30
Number of tender
points
3.2 ⫾1.4 2.5 ⫾1.8
Site of tender points
Neck 16/30 17/30
Shoulder 21/30 20/30
Scapula 24/30 21/30
Decreased neck ROM 30/30 30/30
Sensitive signs 11/30 12/30
Paresthesias 27/30 25/30
Weakness 23/30 21/30
Diminished reflexes 11/30 9/30
Root level C6 18/30 19/30
Root level C7 16/30 14/30
Decreased daily
activities and quality
of life
30/30 30/30
MRI findings
Protrusion of disk 18/30 16/30
Extrusion of disk 2/30 3/30
Foraminal stenosis 14/30 16/30
EMG consistent
findings
19/30 18/30
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Konstantinovic et al.

therapy in group B, which is shown as the median [25%,
75%]. Both groups showed statistically significant values
obtained after therapy in comparison with the baseline
values for all investigated parameters (P<0.001).
Differences between the baseline values obtained prior to
therapy and those obtained at the end of the therapy for
each measured outcome are compared between the two
groups in Table 4. Between groups is represented on
Table 4. Statistical analyses show greater improvement in
group A than in group B for all measured outcomes
except neck pain, with a high effect size on VAS-arm
(d =0.98) and range of extension in neck (d =1.09).
Table 5 represents the distribution of improvement in pain
scores at the end of therapy. These were defined as
greatly improved (<-50 mm), much improved (-50 to
-30 mm), somewhat improved (-30 to -10 mm), about
the same (-10 to 1 mm), and worse (>1 mm).
Ordinal regression analyses for pain intensity in the arm
and neck are presented in Table 6. The analyses show a
significant relationship between the level of pain in the arm
and the treatment group. After treatment, patients in
group A were more likely to have lower levels of arm pain
that those in group B (Odds ratio =5.8). No effect of group
was seen on pain intensity in the neck at the end of
treatment (P=0.09).
Systematic monitoring of adverse effects showed transi-
tional worsening of pain in 6/30 (20%) patients, persistent
nausea in 1/30 (3.33%), and an increase blood pressure in
1/30 (3.33%). All adverse effects occurred in the active
laser group (group A). Transitional worsening of pain was
registered immediately after the first three sessions of
treatment and had a maximum duration of 6 hours.
Patients with nausea or increased blood pressure were
excluded from the study. The results of the monitoring of
side effects show the low-risk nature of LLLT.
Table 3 Mean and median values for outcomes
Group Group A (n =30) Group B (n =30)
Outcomes Pre-therapy Post-therapy Statistics* Pre-therapy Post-therapy Statistics*
VAS-arm†74.06 ⫾4.91 44.29 ⫾5.44 t =38.12 72.52 ⫾5.98 47.84 ⫾7.37 t =20.22
VAS-neck‡56.84 ⫾12.61 33.35 ⫾8.73 t =10.03 58.45 ⫾11.01 39.45 ⫾11.03 t =12.67
NDI§67.65 ⫾6.0 37.81 ⫾7.05 t =21.28 66.87 ⫾5.07 41.74 ⫾4.25 t =23.09
Flexion¶31.87 ⫾3.82 20.29 ⫾3.44 t =20.68 30.61 ⫾4.65 21.29 ⫾4.29 t =14.17
Extension** 39.58 ⫾5.11 37.68 ⫾4.56 t =18.87 26.58 ⫾4.54 27.74 ⫾4.16 t =23.25
PCS†† 11.09 ⫾1.76 16.09 ⫾1.58 t =-16.44 11.03 ⫾1.14 15.13 ⫾1.09 t =-26.22
MCS‡‡ 10.03 ⫾1.45 13.84 ⫾1.19 t =-18.17 9.0 [9.0, 9.0] 12.0 [12.0, 13.0] Z =-5.05
*P<0.001 for all measured outcomes.
Values represented the mean values ⫾SD except for the MCS of group B, where the values represent the median [25%, 75%];
†VAS arm; ‡VAS neck; §The NDI; ¶flexion of neck; ** extension of neck; †† PCS; ‡‡ MCS.
VAS =visual analog scale; NDI =neck disability index; PCS =physical component summary; MCS =mental component summary.
Table 4 Statistical analyses of measured changes
Group
Outcomes
A B A–B
Mean ⫾SD
Mean (SD) or median
(25% 75%) t or Z Pd†
VAS-arm 29.77 ⫾4.35 26.68 ⫾6.79 3.518 0.001* 0.98
VAS-neck 23.35 ⫾11.3 19.0 ⫾7.21 1.806 0.077 No
NDI 29.84 ⫾7.81 25.13 ⫾6.06 2.654 0.01* 0.69
flexion 11.58 ⫾3.12 9.32 ⫾3.66 2.613 0.011* 0.68
extension 13.06 ⫾3.86 9.94 ⫾2.38 3.845 0.000* 1.09
PCS 5.0 ⫾1.69 4.0 [4.0, 5.0]‡-3.17‡0.002* 0.40
MCS 3.81 ⫾1.17 3.0 [3.0, 3.0]‡-2.28‡0.023* 0.29
* Statistically significant values (P>0.05); abbreviations of outcomes are explained in Table 3.
†d (Cohen effect size: d <0.2 =low, 0.2 <d<0.8 =medium, d >0.8 =high).
‡For outcome data that were not distributed normally (PCS and MCS group B), the median (25% 75%) and Zvalue are shown.
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Low-Level Laser Therapy for Acute Neck Pain

Discussion
The lack of evidence with regard to diagnostic procedures
and treatment interventions for a condition that occurs as
frequently as degenerative cervical radiculopathy is very
distressing. The main characteristics of published trials are
imprecise selection of patients with cervical radiculopathy
non-confirmed with additional MRI and EMG investiga-
tions, with different clinical characteristics, undefined clini-
cal stage, and usually lacking description of treatment.
This study included patients with severe pain, moderate
disability, and discomfort during daily activities that were
associated with acute radicular lesion caused by disk
herniation or degenerative changes confirmed with MRI.
Baseline demographic characteristics (Table 2) were
similar to published data and showed an increased preva-
lence in females. Clinical examination prior to treatment
revealed that lesions were predominantly at the level of the
C6 root and that the patients presented frequently with
tender points behind the medial border of the scapula on
the involved side. These findings were particulary incon-
sistent with the published data [41]. The diagnoses in this
study were made mainly on clinical grounds with high
levels of support from consistent MRI findings. However, in
the majority of cases, the neurophysiological examination
did not provide consistent supporting evidence. The
results showed a statistically significant improvement in
the VAS score for arm pain, the parameters for neck
movement, and the PCS score (Table 5) in group A in
comparison with group B. Ordinal regression analyses of
categorized pain intensity showed very clear differences
between the groups, with greater improvement in the
active laser group with respect to arm pain (odds
ratio =5.8). In a study of acute pain, the minimum clinically
relevant change in pain intensity was found to be 13 mm
on the VAS [42,43], and in this study, the changes in VAS
for both the arm and neck were greater than this threshold
value in the majority of patients in both groups (Table 5).
The intensity of neck pain decreased in a statistically sig-
nificant manner in both groups with no intergroup differ-
ences. Statistically significant decreases were measured
for the NDI. This decrease was larger for group A, in which
disability improved from moderate severe to moderate.
The placebo response in this study was similar for the
parameters investigated; for pain in the arm and NDI, it
was approximately 30% (calculated as the difference
between the values obtained prior to treatment and those
obtained at the end of therapy).
The main problem in comparing the results of this study
with the results of other studies of conservative treatment,
particularly LLLT studies, are the differences in included
patients and applied treatments [25]. The study of Soriano
et al. [44], which examined the effectiveness of 10 laser
treatments (wavelength 904 nm, average power 40 mW,
frequency 10,000 Hz, and energy density 4 J/cm2)was
similar in design to this study and showed significant
improvement in 71 patients at the end of treatment and 6
months later. Many other clinical studies have used LLLT
for nonspecific chronic neck pain and myofascial neck
pain [45–49]. The group of patients with nonspecific
chronic neck pain is very heterogeneous, and the genesis
of their pain is caused not only by pathological changes
in spinal and paraspinal structures but also by complex
neurophysiological and psychosocial mechanisms. In
addition, well-designed trials on other conservative treat-
ments of cervical radiculopathy have not been performed.
Persson et al. [16] conducted a randomized clinical trial
that compared three modes of treatment. Patients with
long-lasting cervical radiculopathy were randomized for
surgery, physiotherapy, or use of a cervical collar. Surgery
provided superior pain relief on follow-up at 4 months.
However, on follow-up at 16 months, the three groups
were not different with regard to pain, muscular strength,
or sensory loss. In 1966, the British Association of Physi-
cal Medicine conducted a randomized clinical trial that
included 493 patients with cervical root symptoms. They
were treated with traction, placebo traction, collar,
placebo tablets, or placebo heat treatment [31]. Seventy-
Table 5 Overall change in pain levels for
VAS-arm and VAS-neck
Change in
pain level
Group A
(n =30)
Group B
(n =30)
Overall change in pain level in arm
Greatly improved 0/30 (0%) 0/30 (0%)
Much improved 18/30 (60%) 6/30 (20%)
Somewhat
improved
11/30 (36.66%) 22/30 (73.33%)
About the same 0/30 (0%) 2/30 (6.66%)
Worse 1/30 (3.33%) 0/30 (0%)
Overall change in pain level in neck
Greatly improved 1/30 (3.33%) 3/30 (10%)
Much improved 9/30 (30%) 0/30 (0%)
Somewhat
improved
18/30 (60%) 26/30 (86.66%)
About the same 2/30 (6.66%) 1/30 (3.33%)
Worse 0/30 (0%) 0/30 (0%)
Table 6 Ordinal regression for VAS-arm and
VAS-neck
Group
Estimate
coefficient
Odds
ratio Wald
P
value
95% CI
for odds
ratio
VAS-arm
A-1.753 5.77 9.056 0.003 (0.06, 0.54)
B* 0 1 ———
VAS-neck
A-1.033 2.81 2.828 0.093 (0.11, 1.19)
B* 0 1 ———
* Reference group for this parameter.
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Konstantinovic et al.

five percent of patients in all treatment groups reported
pain relief on follow-up at 4 weeks, and no significant
difference was observed in pain or in ability to work
between the five groups. A recent systematic review on
exercise for patients with neck pain (with or without
radicular arm pain) included specific exercises that may
only be effective for mechanical neck disorders [50]. A
systematic review that examined the effect of manipula-
tion and mobilization techniques in patients with mechani-
cal neck disorders [51] showed that manual therapy
probably results in greater short-term pain relief than exer-
cise therapy or the usual medical care that is given for
atypical neck pain without radiculopathy. However, insuf-
ficient evidence was found for the beneficial effect of
manipulative techniques in the subgroup with cervical
radiculopathy [52]. Moreover, cervical spine manipulation
carries a risk of complications, such as vertebral artery
dissection and spinal cord compression due to massive
disk herniation [53].
Hypothetically, the biological actions of LLLT are multiple.
Studies have documented changes in biochemical
markers of inflammation [54], the distribution of inflam-
matory cells, and a reduction in the occurrence of
edema, hemorrhage, and necrosis after local laser irra-
diation with different sources of laser beams (wave-
lengths of 660 and 684 nm [55], 780 nm [56], and
904 nm [57]) in experimentally induced models of inflam-
mation. The reduction in inflammatory infiltration (appro-
ximately 30–50%) is greatest after 3 to 4 hours and
correlates positively with a dose-dependent reduction in
tumor necrosis factor alpha (TNFa) [58]. Effects on anti-
oxidative enzymes could also be part of the modulation
mechanism in view of the role of these enzymes in
increasing the nonspecific resistance of cells to different
types of damages [59]. Comparison of LLLT with anti-
inflammatory drugs, such as meloxicam and indome-
thacin, has shown that the laser treatment has similar
anti-inflammatory effects to the drugs [60]. Important
additional effects may include a direct influence on neural
structures that are damaged by compression or inflam-
mation [28]. Laser phototherapy of injured peripheral
nerves significantly improves nerve recovery in rat [29]
and in clinical studies [30]. LLLT may have a direct effect
on nerve structures, which could increase the speed of
recovery of the conductive block or inhibit A-d and C
fiber transmission [61,62]. It is possible that laser-induced
neural blockade may then lead to a long-term alteration
in nociception [63], analogous to the prolonged analgesia
seen in some patients after the administration of local
anesthetics [64] and changes at the endorphin level [65].
However, the neuromodulation effects of LLLT are
dependent on many conditions in relation to timing and
mode of irradiation and rarely have been observed for
904 nm laser sources.
The results of this study must be considered in the light
of several limitations. Patients with relatively strictly
defined clinical forms of the condition (severe levels of
pain and moderate severe levels of disability) were
selected due to the typical flow of patients to clinical
treatment (selection bias). Randomization did not include
initial level of disability, MRI and EMG findings, duration of
symptoms, or other psychosocial characteristics that
could influence the therapeutic response. The results of
this study suggest only short-term effects. The identifica-
tion of true positive effects and a placebo response
under conditions of this study is controversial given that
we had no untreated group, especially when the history,
level, and percentage of spontaneous recovery were
unknown.
Future studies could include patients that are randomized
by levels for baseline disability, duration of symptoms, and
other physical and psychosocial characteristics that could
influence the response to treatment. In addition, further
long-term studies could be designed that compare the
use of a single type of therapy with a combined therapy
approach. Further understanding of the mechanisms of
the effects of LLLT could be very important for clinical
recommendation.
Conclusions
The suitability of LLLT (wavelength of 905 nm and dose of
2 J per point) as a monotherapy for the treatment of acute
neck pain with radiculopathy was examined. Patients
treated with LLLT showed a greater improvement in local
neck movements, a more significant reduction of pain
intensity and related disability, and a greater improvement
in quality of life, in comparison with patients treated with a
placebo LLLT procedure. In addition, no major side effects
were observed.
Acknowledgments
The authors would like to thank the Institute for Physics
Belgrade, in particular Professor Milesa Sreckovic, for
technical assistance.
Disclosure Statement
No competing financial interests exist.
References
1 Radhakrishnan K, Litchy WJ, O’Fallon WM, Kurland
LT. Epidemiology of cervical radiculopathy. A popula-
tion based study from Rochester, Minnesota, 1976
through 1990. Brain 1994;117:325–35.
2 Salemi G, Savattieri G, Meneghini F, et al. Prevalence
of cervical spondylotic radiculopathy: A door-to-door
survey in a Sicilian municipality. Acta Neurol Scand
1996;93:184–8.
3 Tanaka N, Fujimoto Y, An HS, Ikuata Y, Yasuda M. The
anatomic relation among the nerve roots, interverte-
bral foramina, and intervertebral discs of the cervical
spine. Spine 2000;25:286–91.
4 Saal JS. The role of inflammation in lumbar pain. Spine
1995;20:1821–7.
1175
Low-Level Laser Therapy for Acute Neck Pain

5 Grönblad M, Virri J, Tolonen J, et al. A controlled
immunohistochemical study of inflammatory cells in
disc herniation tissue. Spine 1994;19:2744–51.
6 Daffner SD, Hilibrand AS, Hanscom BS, et al. Impact
of neck and arm pain on overall health status. Spine
2003;28:2030–5.
7 Wainner RS, Fritz JM, Irrgang JJ, et al. Reliability and
diagnostic accuracy of the clinical examination and
patient self-report measures for cervical radiculopathy.
Spine 2003;28:52–62.
8 Rubinstein SM, Pool JJM, van Tulder MW, Riphagen II,
de Vet HCW. A systematic review of the diagnostic
accuracy of provocative tests of the neck for diagnos-
ing cervical radiculopathy. Eur Spine J 2007;16:307–
19.
9 Carette S, Fehlings MG. Clinical practice. Cervical
radiculopathy. N Eng J Med 2005;353:392–9.
10 Nordin M, Carragee EJ, Hogg-Johnson S, et al.
Assessment of neck pain and its associated disorders:
Results of the Bone and Joint Decade 2000–2010
Task Force on Neck Pain and Its Associated Disor-
ders. Spine 2008;33:S101–22.
11 Bush K, Chaudhuri R, Hillier S, Penny J. The patho-
morphologic changes that accompany the resolution
of cervical radiculopathy. A prospective study with
repeat magnetic resonance imaging. Spine 1997;22:
183–6.
12 Vinas FC, Wilner H, Rengachary S. The spontaneous
resorption of herniated cervical discs. J Clin Neurosci
2001;8:542–6.
13 Korthals-de Bos IBC, Hoving JL, van Tulder MW, et al.
Cost effectiveness of physiotherapy, manual therapy
and general practitioner care for neck pain: Economic
evaluation alongside a randomised, controlled trial.
BMJ 2003;326:911–4.
14 Saal JS, Saal JA, Yurth EF. Nonoperative manage-
ment of herniated intervertebral cervical disc with
radiculopathy. Spine 1996;21:1877–83.
15 Sampath P, Bendebba M, Davis JD, Ducker T.
Outcome in patients with cervical radiculopathy: Pro-
spective multicenter study with independent clinical
review. Spine 1999;24:591–7.
16 Persson LCG, Carlsson CA, Carlsson JY. Long lasting
cervical radicular pain managed with surgery, physio-
therapy or a cervical collar: A prospective, randomized
study. Spine 1997;22:751–8.
17 The Philadelphia Panel Members and Ottawa
Methods Group. Philadelphia panel evidence-based
clinical practice guidelines on selected rehabilitation
interventions for neck pain. Phys Ther 2001;81:1701–
17.
18 Guzman J, Haldeman S, Carroll LJ, et al. Clinical prac-
tice implications of the results of the Bone and Joint
DECADE 2000–2010 Task Force on Neck Pain and its
Associated Disorders: From concepts and findings to
recommendations. Eur Spine J 2008;17:S199–213.
19 Autio RA, Karppinen J, Niinimäki J, et al. The effect of
infliximab, a monoclonal antibody against TNF-[alpha],
on disc herniation resorption: A randomized controlled
study. Spine 2006;31:2641–5.
20 Hubbard RD, Quinn KP, Martínez JJ, Winkelstein BA.
The role of graded nerve root compression on axonal
damage, neuropeptide changes, and pain-related
behaviors. Stapp Car Crash J 2008;52:33–58.
21 Hubbard RD, Winkelstein BA. Dorsal root compres-
sion produces myelinated axonal degeneration near
the biomechanical thresholds for mechanical behav-
ioral hypersensitivity. Exp Neurol 2008;212:482–9.
22 Wehling P, Cleveland SJ, Heininger K, et al. Neuro-
physiologic changes in lumbar nerve root inflammation
in the rat after treatment with cytokine inhibitors:
Evidence for a role of interleukin-1. Spine 1996;21:
931–5.
23 Starkweather A, Witek-Janusek L, Mathews HL.
Neural–immune interactions: Implications for manage-
ment in patients with low back pain and sciatica. Biol
Res Nurs 2005;6:196–206.
24 Bjordal JM, Couppé C, Ljunggren AE. Low-level laser
therapy for tendinopathy. Evidence of a dose-
response pattern. Phys Ther Rev 2001;6:91–9.
25 Bjordal JM, Couppé C, Chow RT, Tunér J, Ljunggren
EA. A systematic review of low-level laser therapy with
location specific doses for pain from chronic joint dis-
orders. Aust J Physiother 2003;49:107–16.
26 Reis SR, Medrado AP, Marchionni AM, et al. Effect of
670-nm laser therapy and dexamethasone on tissue
repair: A histological and ultrastructural study. Pho-
tomed Laser Surg 2008;26:307–13.
27 Vasheghani MM, Bayat M, Rezaei F, Bayat A, Karimi-
pour M. Effect of low-level laser therapy on mast cells
in deep second-degree burns of rats. Photomed Laser
Surg 2008;26:1–5.
28 Gigo-Benato D, Geuna S, Rochkind S. Phototherapy
for enhancing peripheral nerve repair: A review of the
literature. Muscle Nerve 2005;31(6):694–701.
1176
Konstantinovic et al.

29 Rochkind S, Barrnea L, Razon N, Bartal A, Schwartz
M. Stimulatory effect of He-Ne low dose laser on
injured sciatic nerves of rats. Neurosurgery 1987;20:
843–7.
30 Rochkind S, Drory V, Alon M, Nissan M, Ouaknine GE.
Laser phototherapy (780 nm), a new modality in treat-
ment of long-term incomplete peripheral nerve injury:
A randomized double-blind placebo-controlled study.
Photomed Laser Surg 2007;25:436–42.
31 The British Association of Physical Medicine. Pain in
the neck and arm: A multicentre trial of the effects of
physiotherapy. BMJ 1966;1:253–8.
32 Binder AI. Cervical spondylosis and neck pain. BMJ
2007;334:527–31.
33 Lopes-Martins RA, Albertini R, Lopes-Martins PS,
et al. Steroid receptor antagonist mifepristone inhibits
the anti-inflammatory effects of photoradiation. Pho-
tomed Laser Surg 2006;24:197–201.
34 Magee DJ. Cervical spine. In: Magee DJ, ed. Ortho-
pedic Physical Assessment, 3rd edition. Philadelphia,
PA: W.B. Saunders; 1997:101–51.
35 Shah KC, Rajshekhar V. Reliability of diagnosis of soft
cervical disc prolapse using Spurling’s test. Br J Neu-
rosurg 2004;18:4480–3.
36 Scott J, Huskisson E. Graphic representation of pain.
Pain 1976;2:175–84.
37 Bijur PE, Silver W, Gallagher EJ. Reliability of the visual
analog scale for measurement of acute pain. Acad
Emerg Med 2001;8:1153–7.
38 Collins SL, Moore RA, McQuay HJ. The visual ana-
logue pain intensity scale: What is moderate pain in
millimetres? Pain 1997;72:95–7.
39 Vernon H, Mior S. The neck disability index: A study of
reliability and validity. J Manipulative Physiol Ther
1991;14:409–15.
40 Ware JE, Kosinski M, Keller SD. A 12-item short form
health survey. Med Care 1996;34:220–33.
41 Henderson CM, Hennessy RG, Shuey HM, Shackel-
ford EG. Posterior-lateral foraminotomy as an exclu-
sive operative technique for cervical radiculopathy: A
review of 846 consecutively operated cases. Neuro-
surgery 1983;13:504–12.
42 Todd KH, Funk KG, Funk JP, Bonacci R. Clinical sig-
nificance of reported changes in pain severity. Ann
Emerg Med 1996;27:485–9.
43 Fejer R, Jordan A, Hartvigsen J. Categorising the
severity of neck pain: Establishment of cut-points for
use in clinical and epidemiological research. Pain
2005;119:176–82.
44 Soriano F, Rios R, Pedrola M, Giagnorio J, Battagliotti
C. Acute cervical pain is relieved with Gallium Arsenide
(GaAs) laser radiation. A double-blind preliminary
study. Laser Ther 1996;8:149–54.
45 Altan L, Bingöl U, Aykaç M, Yurtkuran M. Investigation
of the effect of GaAs laser therapy on cervical myo-
fascial pain syndrom. Rheumatol Int 2005;25:23–7.
46 Ozdemir F, Birtane M, Kokino S. The clinical efficacy of
low-power laser therapy on pain and function in cer-
vical osteoarthritis. Clin Rheumatol 2001;20:181–4.
47 Chow RT, Heller GZ, Barnsley L. The effect of
300 mW, 830 nm laser on chronic neck pain: A
double-blind, randomized, placebo-controlled study.
Pain 2006;124:201–10.
48 Gur A, Sarac AJ, Cevik R, Altindag O, Sarac S. Effi-
cacy of 904 nm gallium arsenide low level laser
therapy in the management of chronic myofascial pain
in the neck: A double-blind and randomized-controlled
trial. Lasers Surg Med 2004;35:229–35.
49 Chow RT, Barnsley L. Systematic review of the litera-
ture of low-level laser therapy (LLLT) in the manage-
ment of neck pain. Lasers Surg Med 2005;37:46–52.
50 Kay TM, Gross A, Goldsmith C, et al. Exercises for
mechanical neck disorders. Cochrane Database Syst
Rev 2005;3:CD004250.
51 Gross AR, Hoving JL, Haines TA, et al. Manipulation
and mobilisation for mechanical neck disorders.
Cochrane Database Syst Rev 2004;1:CD004249.
52 Hurwitz EL, Morgenstern H, Harber P, et al. A ran-
domized trial of medical care with and without physical
therapy and chiropractic care with and without physi-
cal modalities for patients with low back pain: 6-month
follow-up outcomes from the UCLA low back pain
study. Spine 2002;27:2193–204.
53 Di Fabio RP. Manipulation of the cervical spine: Risks
and benefits. Phys Ther 1999;79:50–65.
54 Sattayut S, Hughes F, Bradley P. 820 nm gallium alu-
minium arsenide laser modulation of prostaglandin
E2 production in interleukin-1 stimulated myoblasts.
Laser Ther 1999;11:88–95.
55 Albertini R, Villaverde AB, Aimbire F, et al. Anti-
inflammatory effects of low- level laser therapy (LLLT)
with two different red wavelengths (660 nm and
684 nm) in carrageenan-induced rat paw edema. J
Photochem Photobiol 2007;89:50–5.
1177
Low-Level Laser Therapy for Acute Neck Pain

56 Honmura A, Yanase M, Obata J, Haruki E. Therapeutic
effects of Ga-Al-As diode laser irradiation on experi-
mentally induced inflammation in rats. Lasers Surg
Med 1992;12:441–9.
57 Correa F, Lopes-Martins RA, Correa JC, et al. Low-
level laser therapy (GaAs l=904 nm) reduces
inflammatory cell migration in mice with
lipopolysaccharide-induced peritonitis. Photomed
Laser Surg 2007;25:245–9.
58 Aimbire F, Albertini R, Pacheco MT, et al. Loe-level
laser therapy induces dose-dependent reduction of
TNF-alpha levels in acute inflammation. Photomed
Laser Surg 2006;24:33–7.
59 Karu T. Primary and secondary mechanisms of action
of visible to near IR radiation on cells. J Photochem
Photobiol B 1999;49:1–17.
60 Campana V, Moya A, Gavotto A, et al. The relative
effects of He-Ne laser and meloxicam on experimen-
tally induced inflammation. Laser Ther 1999;11:
36–41.
61 Chow RT, David MA, Armati PJ. 830 nm laser irradia-
tion induces varicosity formation, reduces mitochon-
drial membrane potential and blocks fast axonal flow
in small and medium diameter rat dorsal root ganglion
neurons: Implications for the analgesic effects of
830 nm laser. J Peripher Nerv Syst 2007;12:28–39.
62 Tsuchiya K, Kawatani M, Takeshige C, Sato T, Matsu-
moto I. Diode laser irradiation selectively diminishes
slow component of axonal volleys to dorsal roots from
the saphenous nerve in the rat. Neurosci Lett 1993;
161:65–8.
63 Wall PD. New horizons—An essay. In: Bridenbaugh
PO, Cousins MJ, eds. Neural Blockade in Clinical Ana-
esthesia and Management of Pain. Philadelphia, PA:
Lippincott-Raven Publishers; 1998:1135–43.
64 Arnér S, Lindblom U, Meyerson BA, Molander C. Pro-
longed relief of neuralgia after regional anesthetic
blocks. A call for further experimental and systematic
clinical studies. Pain 1990;43:287–97.
65 Laakso EL, Cramond T, Richardson C, Galligan JP.
Plasma Acth and beta-endorphin levels in response to
low level laser therapy (LLLT) for myofascial trigger
points. Laser Ther 1994;6:133–42.
1178
Konstantinovic et al.