LLLT for Ankylosing Spondylitis
LLLT for Ankylosing Spondylitis
ORIGINAL ARTICLE
Abstract This study aimed to compare the effectiveness of passive stretching exercises decreased pain more
the combined low-level laser therapy (LLLT) and passive effectively than placebo LLLT along with the same passive
stretching with combined placebo LLLT laser and the same stretching exercises in patients with Αnkylosing
passive stretching exercises in patients suffering from spondylitis. Future stud- ies are needed to establish the
Αnkylosing spondylitis. Forty-eight patients suffering from relative and absolute effective- ness of the above protocol.
Αnkylosing spondylitis participated in the study and were
ran- domized into two groups. Group A (n = 24) was Keywords LLLT . Ankylosing spondylitis . Passive
treated with a λ= 820 Ga-Al-As laser CW, with power stretching
intensity = 60 mW/ cm2, energy per point in each session =
4.5 J, total energy per session = 27.0 J, in contact with
specific points technique, plus passive stretching exercises.
Introduction
Group B (n = 24), received pla- cebo laser plus the same
passive stretching exercises. Both groups received 12
Ankylosing spondylitis (AS) is the most common of the
sessions of laser or placebo within 8 weeks; two sessions
five subtypes of spondyloarthritides [1]. AS is more
per week (weeks 1–4) and one session per week (weeks 5–
prevalent than undifferentiated spondyloarthritides and
8). Pain and function scales were completed before the
psoriatic arthritis and is a disease that involves joints and
treatment, at the end of the fourth and eighth week of
ligamentous attachments of the spine with the most typical
treatment, and 8 weeks after the end of treatment (follow-
findings to be a result from enthesitis and sacroiliitis [2].
up). Group A revealed a significant improvement after 8
AS is a chronic inflammatory disease that progressively
weeks of treatment in all pain and function scales. At 8-
deteriorate and predominantly affects the spine and may
week follow- up, the improvement remained only for the
cause serious functional impairment. This process is
pain, while for all other function outcomes the differences
characterized by the infiltration of tissue destruction,
were not statistically significant. The results suggested that
mononuclear inflam- matory cells, and attempts at healing
after an 8-week treat- ment and after a follow-up, the
by fibrosis and angio- genesis. Macrophages are the central
combination of LLLT and
and dominant cells in chronic inflammation; they are
activated by clinical mediators such as interferon-γ,
produced by T lymphocytes [3, 4].
* K. Papadopoulos
[email protected] The prevalence of AS is 0.4–1.4 % and affects males
more than female patients with a ratio of about 2:1 to 3:1
and usually starts in the third decade of life [5]. The
1
Physiotherapy Program, Department of Health Sciences, School disease is known to have definite socio-economic
of Sciences, European University Cyprus, Laureate International implications [6].
Universities, 6 Diogenes Street, 2044 Engomi, Nicosia, Cyprus AS treatment aims to reduce morning stiffness and pain;
2
Lab of Health, Fitness and Disability Management, Faculty of to delay the evolution of the disease; to maintain posture;
Human Movement and Quality of Life, University of to prevent malfunction, deformity, disability, and handicap;
Peloponnese, Efstathiou & Stamatikis Balioti & Plateon, 231 00 and preserve physical condition and psychosocial
Sparta,
Laconia, Greece health. Additionally, treatment points to suppress the
inflammation
Lasers Med Sci
Pain
determine the between-group difference (simple main The main effect of the group was statistically significant
effects) at each time point. In the case of the generalized (p < 0.05) for all outcomes indicating significant
mixed effect models, the likelihood ratio test (LRT) was improvement in the treatment group in comparison to the
performed to test for a significant main effect of group and control group. The difference between the treatment and
a significant inter- action between the effect of group and control groups was sta- tistically significant at 8 weeks for
time. all outcomes (the adjusted effect size from mixed ANOVA
The LME4 package of the statistical software R (version was for VAS = −32.5, 95 % confidence interval [CI] =
2.12.1; R Foundation for Statistical Computing, Vienna, −40.0 to −25.0; BASFI = −13.1,
Austria) was used for fitting the generalized mixed effect 95 % CI = −22.2 to −4.1; STEST = 0.7, 95 % CI = 0.1 to
model. All the other analyses were performed using the 1.3;
Predictive Analytics Software Statistics 20 (SPSS Inc, CervR = 15.9, 95 % CI = 6.2 to 25.5; LsideF = 2.2, 95 %
Chicago, IL, USA). Significance test and confidence CI = 0.8 to 3.6; and IntMD = 8.3, 95 % CI = 2.3 to 14.4
intervals were calculated at a significance level of 0.05. while for BASFI and TrwallD, the p values of the adjusted
effect size from the generalized linear mixed models were
p < 0.01). However, with the exception of VAS, the
Results difference between the two groups was not statistically
significant at 8-week fol- low-up for all other outcomes
Sixty-five patients who met the inclusion criteria and had a (the adjusted effect size from mixed ANOVA was for
diagnosis of AS were included in the study. Patient character- VAS = −41.9, 95 % CI = −49.4 to
istics are presented in Table 2. There were no significant dif- −34.5, BASFI = −8.9, 95 % CI = −18.1 to 0.1; STEST =
ferences in gender, age, DISDUR, ESR, and baseline mea- 0.5,
surements between the treatment and control groups (Table 95 % CI = −0.1 to 1.1; CervR = 4.9, 95 % CI = −4.7 to
1). 14.6;
The interaction between the effect of group and time LsideF = 1.1, 95 % CI = −0.3 to 2.5; and IntMD = 4.3, 95
was statistically significant only for two outcomes, %
BASFI (F(3138) = 2.84, p = 0.04) and Tragus to wall CI = −1.8 to 10.4 while the p values of the adjusted effect
distance (p for LRT = 0.003). The simple main effects size for BASFI and TrwallD were 0.36 and 0.14,
analysis with linear contrasts showed that there was respectively).
significant difference between treatment and control
groups at 8 weeks (p < 0.01) for both outcomes, but there
was no difference between the two groups at 4- and 8-week Discussion
follow-up (Tables 3 and 4).
Τhe present study was conducted to ascertain whether a
combination of LLLT with passive stretching for 8 weeks
and an 8-week follow-up period for patients with anky-
losing spondylitis, would indicate any effects on pain and
Table 2 Anthropometric
characteristics and baseline Variable Treatment (n = 24) Control (n = 24) p value
measurements of the treatment
and control groups (n = 48) Gender, n (%)
Male 14 (58.3 %) 15 (62.5 %) 0.77†
Female 10 (41.7 %) 9 (37.5 %)
Age 46.4 (7.5) 47.0 (8.9) 0.59+
DISDUR 8.9 (2.6) 8.0 (2.8) 0.58+
ESR, median (IQR) 28.8 (17.6) 35.0 (21.9) 0.22*
VAS 70.0 (14.9) 67.5 (15.8) 0.59+
BASFIα 51.5 (16.7) 48.6 (17.5) 0.55+
Schöber test 2.2 (0.9) 2.2 (1.0) 0.91+
Cervical rotation 51.3 (17.9) 49.5 (19.9) 0.73+
Lumbar side flexion 4.8 (2.1) 5.0 (2.2) 0.66+
Intermalleolar distance 80.9 (11.4) 77.5 (21.7) 0.53+
Tragus to wall distance, median (IQR) 5.8 (3.3) 5.3 (3.3) 0.56*
BASDAI, median (IQR) 28.2 (13.3) 25.9 (12.0) 0.42*
Table 3 Results of analysis comparing outcomes between treatment and control groups
Outcome variable Unadjusted mean (SD) for each group Unadjusted Mean p value Adjusted mean difference p value
Difference between groups† (95 %
between groups (95 % CI) CI)
Treatment Control
VAS
4 weeks 52.9 (14.8) 66.5 (15.2) −13.6 (−22.3, −4.9) <0.01 −13.6 (−21.0, −6.1) <0.01
8 weeks 33.1 (8.6) 65.6 (14.3) −32.5 (−39.4, −25.6) <0.01 −32.5 (−40.0, −25.0) <0.01
8 weeks follow-up 26.7 (6.8) 68.6 (11.7) −41.9 (−47.5, −36.5) <0.01 −41.9 (−49.4, −34.5) <0.01
BASFI
4 weeks 41.7 (15.4) 46.5 (16.9) −4.8 (−14.1, 4.6) 0.31 −4.8 (−13.9, 4.3) 0.30
8 weeks 37.4 (13.7) 50.6 (15) −13.2 (−21.7, −4.6) <0.01 −13.1 (−22.2, −4.1) <0.01
8 weeks follow-up 43.9 (15.6) 52.8 (16.4) −8.9 (−18.2,0.4) 0.06 −8.9 (−18.1, 0.1) 0.05
Schöber test
4 weeks 2.6 (1.1) 2.2 (1.0) 0.4 (−0.2, 1.0) 0.20 0.4 (−0.2, 1.0) 0.21
8 weeks 2.8 (1.6) 2.1 (0.9) 0.7 (−0.0, 1.5) 0.06 0.7 (0.1, 1.3) 0.02
8 weeks follow-up 2.7 (1.0) 2.2 (0.9) 0.5 (−0.1, 1.1) 0.07 0.5 (−0.1, 1.1) 0.10
Cervical rotation
4 weeks 59.3 (17.1) 47.4 (18.9) 11.9 (1.4, 22.4) 0.03 11.9 (2.2, 21.5) 0.02
8 weeks 66.1 (14.1) 50.2 (16.0) 15.9 (7.1, 24.6) <0.01 15.9 (6.2, 25.5) <0.01
8 weeks follow-up 58.5 (15.4) 53.6 (16.3) 4.9 (−4.3, 14.1) 0.29 4.9 (−4.7, 14.6) 0.32
Lumbar side flexion
4 weeks 5.8 (2.9) 4.9 (2.2) 0.9 (−0.6, 2.4) 0.22 0.9 (−0.5, 2.3) 0.19
8 weeks 7.4 (2.9) 5.2 (2.2) 2.2 (0.7, 3.7) <0.01 2.2 (0.8, 3.6) <0.01
8 weeks follow-up 6.1 (2.9) 5.0 (1.9) 1.1 (−0.3, 2.5) 0.13 1.1 (−0.3, 2.5) 0.13
Intermalleolar distance
4 weeks 86.8 (8.3) 77.0 (10.8) 9.7 (4.1, 15.3) <0.01 9.7 (3.7, 15.8) <0.01
8 weeks 89.8 (11.6) 81.4 (10.6) 8.3 (1.9, 14.8) 0.01 8.3 (2.2, 14.4) <0.01
8 weeks follow-up 84.2 (10.7) 79.9 (10.4) 4.3 (−1.8, 10.4) 0.16 4.3 (−1.8, 10.4) 0.16
functional activities of the patients. The parameters condition and their modulation at the early stages may
followed were daytime pain intensity, the BASMI, slow the progression of AS. However, the planning of
BASFI, and BASDAI. After 8 weeks of treatment, all treatment is dependent from severity, the localization, the
the above-mentioned parameters showed significant im- manifestation, and the degree of progress of AS [1, 2].
provement in comparison with placebo laser with passive Anti-inflammatory medications such as indomethacin,
stretching. These differences remained unchanged in the diclofenac, novel more COX-2-selective agents, cortico-
follow-up period only for the pain perception, while in the steroids, and biological therapy with agents directed
other outcomes, although remained changed, the differ- against tumor necrosis factor-alpha (TNF-a), seem to have
ences between the two groups were not statistically an effect in the pain perception and in the other symptoms
significant. of AS patients. However, these biological agents have
A serious symptom of inflammation in AS patients is various side effects and its clinical use is questioned and
pain which is produced by pro inflammatory cytokines. For limited [48].
exam- ple, interleukin-6, increases the sensitization of thin LLLT is the modality used in rehabilitation departments
myelinat- ed A delta fibers and unmyelinated C fibers to decrease inflammation and pain. It is believed that LLLT
innervating the joint [46]. Additionally, tumor necrosis acts similarly as the effects of nonsteroidal anti-
factor-alpha (TNF-a), and interleukin-1beta (IL-1β), inflammatory ste- roids and drugs. Laser light enhances the
contribute to pain hypersensi- tivity [47]. blood concentration of B-endorphins, reduces the level of
Thus, the treatment options are the suppression of the prostaglandin E2, and inhibits the release cyclo-oxygenase.
in- flammatory mediators, that are increased in the Also, it modulates nerve transmission [16–20, 49].
diseased
Lasers Med Sci
However, the exact mechanisms by which LLLT Kingsley et al. [63], and Yousefi-Nooraie et al. [64] in the
alleviates pain is not fully understood. It is believed that reviews.
laser irradiation causes a series of reactions in biological However, in spite of the above-mentioned positive LLL
tissues. Increase in NO, which is beneficial in the healing effects, Chou and Huffman supported that LLLT may not
process since its in- crease at the inflammation site, would be beneficial for spondyloarthritides [65].
improve the local in- flammation [50, 51]. With regards to AS, only one study by Aydin et al. [66]
LLLT causes an increase in the metabolism of cells such was found. The authors studied the effects of GaAlAs, λ =
as a release of growth factors, upregulation of ATP, 810 nm, 30 mW in the treatment of patients with AS. They
cytokine reactions, an increase in reactive oxygen species measured pain, functional status, and disease activity in 37
(ROS) and therefore cell proliferation [52]. (19 experi- mental and 18 control) patients with AS. In the
AS is reported to affect cervical, thoracic, and lumbar skin contact method used in 10 sessions, they delivered 1.2
spine. Typically, osteoarthritis of spine zygapophyseal J per point on the L3 to S1 supra spinous ligaments and
joints manifests inflammation, pain, and restricted move- sacroiliac joints bilaterally. These investigators did not find
ments. The distance between skin and lateral aspect of significant differ- ences in the measurement parameters
joint surface is for cervical spine about 3 cm, while for between the placebo and control groups.
the lumbar spine 7 cm. Laser 820 nm of our study param- The negative results of the above-mentioned study were
eters can penetrate several centimeters at these joints and mainly due to different lasers being used and differences in
can decrease inflammation and consequent the pain inten- the treatment parameters. We hypothesized that the patients
sity [53]. with AS would show better results in all BASMI, BASFI,
Bad posture, that characterizes AS patients, cause and BASDAI and VAS scores, if along with the laser
fatigue and increases the oxidative stress in the erector treatment passive stretching was applied at the same time.
spine muscles. Muscle fatigue is the precursor of muscle The finding that LLLT, together with passive stretching,
pain because the ischemia impairs microcirculation. Laser reduced significantly the five symptoms of BASDAI
with light doses, which is used for inflammatory purposes, (fatigue, morning stiffness, tenderness, and spinal or joint
can delay the in- flammation process and preserve the pain), at the end of the intervention and remained slightly
physiology of spine curves by decreasing the oxidative improved in the follow-up, indicates that this protocol
stress and muscle fatigue [54–56]. plays an important role in the treatment of AS patients.
Several studies investigated the efficacy of different The results also showed an increase in physical
phys- ical therapy modalities such as LLLT and exercise in functions as presented by BASFI. It seems that this
patients suffering from spondyloarthritides reporting improvement is due to the reduction in pain intensity
positive and neg- ative effects. during daily activities that was caused by LLLT.
For example, Konstantinovic et al. [57], Jovicic et al. Also, the results demonstrated an increase in mobility,
[58], Djavid et al., [59], Fiore et al. [60], and Ay [61] functional capacity, and activity, reported by the modified
investigated the effects of 904-nm low-level laser with Schöber test, tragus to wall distance, lumbar side flexion,
different doses and energy density in patients suffering cer- vical rotation, and intermalleolar distance.
from acute or chronic low back pain or back pain with Literature search revealed that the effect of
radiculopathy and reported good effects. Similar were the physiotherapy with exercise as main component was
conclusions of Fulop et al. [62], mostly investigated, in
Lasers Med Sci
the treatment of AS. Therefore, the results of the present energy delivering per point, per treatment session, and the
study are most comparable with these studies. total session energy [78–80].
For example Kjeken et al. [67], Aytekin et al. [68], Altan Several steps to avoid these methodological errors were
et al. [69], Strumse et al. [70], Rosu et al. [71], and taken. AS patients were recruited from a large rural region.
Rodriguez- Lozano et al. [72] studied the effects of It is believed that our subjects are representative, as a
different exercise types such as home-based exercise, homog- enous population lives in Peloponnese prefecture.
Pilates, McKenzie and Heckscher training and Out of 65 patients initially enrolled, 24 completed the
physiotherapy. These authors mea- sured the same experimental pro- tocol; It is thought that this number is
parameters of the present study. They showed a significant high if taking in account that the prevalence of AS is low
improvement in the fatigue, morning stiffness, tenderness, and patients are hard to find. The laser intensity and
and spinal or joint pain (BASDAI); in mobility, functional duration of every session were stan- dardized and
capacity, and activity (BASMI); and in physical function quantified, and ensured that the patients follow- ed strictly
(BASFI) and pain which remained after the follow- up to the intervention. Finally, an 8-week follow-up period
periods. was included, that is generally acceptable by patients in
Besides the aforementioned studies, the current clinical studies, since it is not ethical to leave the placebo
literature showed many reviews that further strengthened laser group, without treatment for a long time (more than 8
the view that physical therapy has positive effects in weeks). This length of time can usually be tolerated by
patients suffering from AS (Elvan and Khan [73], patients with- out undue distress, compared to longer time
Passalent [74], Dagfinrud et al. [75], Giannoti et al. [76]). [35, 77]. Another significant advantage of this study was
It was decided that the present study would include the specific spine point, which is either trigger, motor, or
passive stretching exercises in order to strength the acupuncture points for irradiation were used. Simons, et al.
interaction be- tween the group and time effect. The [81] confirmed the characteristics of relationship of the
stretching program per- formed satisfactorily in the specific points that are the following: tenderness to
treatment sessions, because this maneuver accelerates palpation in the presence of segmen- tally related
collagen realignment [23, 77]. Passive stretching activate pathology, decrease resistance to electricity, in- creased
the stress/relaxation phenomenon and im- prove function resistance to pressure (hardness, firmness, muscle guarding
of the erector spine muscles [35]. It is believed that or spasm), anatomically situated, near, or over su- perficial
because of inflammation, free nerve endings of the area are nerve fibers and blood vessels, contain fibrositic
irritated and produce pain, which does not allow the AS components, give rise to referred pain on pressure, exists
patient to use the spine in concrete motions. Passive an- atomically at similar locations, and represent or are
stretching can improve and realign the collagen fibers in located at dense groupings of sensory end organs, on or
muscles, fascia, ligaments, and in the other soft tissues of just below the skin surface.
the spine [28]. At the end of the present investigation, our Τhe patients of our study who received LLLT were
protocol was offered to all of the AS patients. All accepted improved with regards to pain, but there was no signifi-
and all improved. Twelve treatments were sufficient to cant difference in comparison with the placebo laser sub-
elicit a significant change. Further improvement was jects in other parameters, supporting the view that the
achieved in pain during follow-up period by continuing the laser treatment has analgesic effects. The analgesia pro-
passive stretching exercises, all pa- tients being kept on vided by laser treatment allows other therapeutic proce-
treatment for at least 8 more weeks. It is not known if this dures such as passive stretching to be performed more
continued improvement also would have occurred if comfortably. Decreasing the pain intensity will gain the
passive stretching exercises been stopped after the end of confidence of the patient and facilitate spine muscles re-
the active laser treatment. Most patients stated that could laxation, which is essential for the process of recovery
be more active during daily activities without pain. and pain improvement [16–20].