A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations
This randomized controlled trial investigated whether low-level laser therapy (LLLT) has an anti-inflammatory effect on activated Achilles tendinitis. Seven patients with bilateral Achilles tendinitis received either active LLLT or placebo LLLT on their two tendons. Prostaglandin E2 (PGE2) concentrations, measured via microdialysis, were significantly reduced after active LLLT compared to placebo and pre-treatment levels, indicating LLLT's anti-inflammatory effect. Pressure pain threshold also increased more after active LLLT than placebo LLLT. The study demonstrates that LLLT can reduce inflammation and pain in activated Achilles tendinitis.
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Corina Bondi, PhD discusses her research on experimental traumatic brain injury and the resulting cognitive deficits.
Traumatic brain injuries (TBIs) affect 2.8 million individuals in the United States each year. Moreover, 500,000 yearly emergency room visits are attributed to childhood-acquired brain trauma, while the elderly also constitute another high-risk population segment due to falls, with patients enduring long-lasting cognitive, physical, or behavioral effects. Impaired attention is central to the cognitive deficits associated with long-term sequelae for many TBI survivors. Considering that cognitive deficits are often assessed using multi-domain neuropsychological cognitive battery tests, Dr. Bondi’s group employed, for the first time, multimodal approaches to determine higher-order attentional capabilities after experimental TBI in rats. Their studies aimed to investigate complex cognitive deficits in adolescent and adult male and female rats subjected to frontal or parietal lobe injuries. Higher-order attentional testing will advance the understanding of long-term cognitive impairments in survivors of brain trauma and may provide reliable avenues towards developing more suitable therapeutic approaches.
Key Topics Include:
Cognitive functioning can be assessed via multiple test modalities in rodents, similar to the clinical setting.
Multiple domains of complex, higher-order cognitive functioning (sustained attention, behavioral flexibility, goal-directed behavior) are mediated by the frontal lobe in rodents in a similar fashion to the human brain, with long-lasting alterations after brain trauma occurring regardless of sex.
Differences between multiple classes of pharmacotherapies employed to restore neurobehavioral and cognitive performance after traumatic brain injury, such as antidepressants and cholinergic drugs.
Still’s Disease and Recurrent Complex Regional Pain Syndrome Type-I: The Firs...Samantha Adcock
Clinical Study
Still’s Disease and Recurrent Complex Regional Pain Syndrome
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C´esar Faillace and Joz´elio Freire de Carvalho
Multimodal Behavioral Assessment After Experimental Brain TraumaInsideScientific
Corina Bondi, PhD discusses her research on experimental traumatic brain injury and the resulting cognitive deficits.
Traumatic brain injuries (TBIs) affect 2.8 million individuals in the United States each year. Moreover, 500,000 yearly emergency room visits are attributed to childhood-acquired brain trauma, while the elderly also constitute another high-risk population segment due to falls, with patients enduring long-lasting cognitive, physical, or behavioral effects. Impaired attention is central to the cognitive deficits associated with long-term sequelae for many TBI survivors. Considering that cognitive deficits are often assessed using multi-domain neuropsychological cognitive battery tests, Dr. Bondi’s group employed, for the first time, multimodal approaches to determine higher-order attentional capabilities after experimental TBI in rats. Their studies aimed to investigate complex cognitive deficits in adolescent and adult male and female rats subjected to frontal or parietal lobe injuries. Higher-order attentional testing will advance the understanding of long-term cognitive impairments in survivors of brain trauma and may provide reliable avenues towards developing more suitable therapeutic approaches.
Key Topics Include:
Cognitive functioning can be assessed via multiple test modalities in rodents, similar to the clinical setting.
Multiple domains of complex, higher-order cognitive functioning (sustained attention, behavioral flexibility, goal-directed behavior) are mediated by the frontal lobe in rodents in a similar fashion to the human brain, with long-lasting alterations after brain trauma occurring regardless of sex.
Differences between multiple classes of pharmacotherapies employed to restore neurobehavioral and cognitive performance after traumatic brain injury, such as antidepressants and cholinergic drugs.
Similar to A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations
Still’s Disease and Recurrent Complex Regional Pain Syndrome Type-I: The Firs...Samantha Adcock
Clinical Study
Still’s Disease and Recurrent Complex Regional Pain Syndrome
Type-I: The First Description
C´esar Faillace and Joz´elio Freire de Carvalho
EXAMINATION OF THE SKIN CONDUCTANCE LEVEL (SCL) AS AN INDEX OF THE ACTIVITY O...ijbesjournal
This paper displays standardized measurements to examine the skin conductance level (SCL) as an index for the sympathetic nervous system’s activity considering a possible standardization of personal variability. SCL measurements were performed at baseline, Cold-Pressor-Tests and Stroop Tests for 15 subjects and inter- and intra-individual mean SCL values were examined. The logarithmic representation displays a high inter-individual variability, denoted by a high fluctuation range of the absolute values and SCL amplitudes. A standardization of inter-individuality could not be achieved by the applied methods (range correction and z-transformation). For the relative intra-individual comparison of the stress situation to the baseline, a method of correction for the determination of the real effect of sympathetic activation was established. EDA should be combined with other parameters of the ANS for a more precise evaluation of stress situations in the context of changes in blood pressure.
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A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations
1. 76
ORIGINAL ARTICLE
A randomised, placebo controlled trial of low level laser
therapy for activated Achilles tendinitis with microdialysis
measurement of peritendinous prostaglandin E2
concentrations
J M Bjordal, R A B Lopes-Martins, V V Iversen
...............................................................................................................................
Br J Sports Med 2006;40:76–80. doi: 10.1136/bjsm.2005.020842
Background: Low level laser therapy (LLLT) has gained increasing popularity in the management of
tendinopathy and arthritis. Results from in vitro and in vivo studies have suggested that inflammatory
modulation is one of several possible biological mechanisms of LLLT action.
Objective: To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human
Achilles tendon.
Subjects: Seven patients with bilateral Achilles tendinitis (14 tendons) who had aggravated symptoms
produced by pain inducing activity immediately before the study.
Method: Infrared (904 nm wavelength) LLLT (5.4 J per point, power density 20 mW/cm2) and placebo
LLLT (0 J) were administered to both Achilles tendons in random blinded order.
Results: Ultrasonography Doppler measurements at baseline showed minor inflammation through
See end of article for
authors’ affiliations increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of
....................... 0.91 (95% confidence interval 0.87 to 0.95). Prostaglandin E2 concentrations were significantly reduced
75, 90, and 105 minutes after active LLLT compared with concentrations before treatment (p = 0.026)
Correspondence to:
Dr Bjordal, Physiotherapy and after placebo LLLT (p = 0.009). Pressure pain threshold had increased significantly (p = 0.012) after
Science, University of active LLLT compared with placebo LLLT: the mean difference in the change between the groups was
Bergen, Bergen, Norway; 0.40 kg/cm2 (95% confidence interval 0.10 to 0.70).
jmbjor@broadpark.no
Conclusion: LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles
Accepted 1 July 2005 tendinitis. LLLT may therefore have potential in the management of diseases with an inflammatory
....................... component.
O
steoarthritis, tendinitis, and painful spinal disorders peritendinous inflammation in normal and symptomatic
are the most common musculoskeletal disorders in tendons.26 27 Although some researchers have questioned
modern society.1–4 A whole range of different treat- the presence of inflammation in chronic tendinopathies,
ments such as locally applied or orally administered drugs, others have shown that structural tendon damage and
electrotherapies, joint mobilisation techniques, exercise ruptures correlate significantly with the degree of inflamma-
therapy, cognitive behavioural therapies, and alternative tion.28–30 In addition, loading of tendon cells increased the
treatments are currently in use for these conditions.5–9 Non- expression of cyclo-oxygenase 2 and the release of prosta-
steroidal anti-inflammatory drugs (NSAIDs) and steroid glandin E2 (PGE2) in vitro and peritendinous PGE2 concen-
injections have been the most prevalent form of treatment trations in a human experimental model of healthy Achilles
for short term pain relief.10–12 Most treatments exhibit some tendons.31 In healthy subjects, this activity induced release of
pain relieving effect against osteoarthritis and tendino- PGE2 could be blocked by a cyclo-oxygenase 2 inhibitor
pathy.13 14 However, it is unclear whether any electrophysical (celecoxib).27 Therefore microdialysis after activity induced
agents have anti-inflammatory effects. A review on the inflammation seems to be a suitable method for assessing the
biological effects of ultrasound therapy suggests that there is anti-inflammatory effect of LLLT in humans.
no evidence that it has any major anti-inflammatory effect.15
For low level laser therapy (LLLT) two important biological MATERIALS AND METHODS
responses have been targeted as possible mechanisms for its Patient sample
beneficial clinical effects in clinical trials on tendinopathy Patients were recruited through primary care doctors and
and osteoarthritis.16 17 The first possible biological response is physiotherapists. Patients who sought help for their bilateral
a modulating, dose dependent effect on fibroblast metabo- Achilles pain were targeted, and given the opportunity to
lism and collagen deposition. This response has been participate before standard treatment was started. Inclusion
observed in a broad range of controlled studies on cell criteria were: signed written informed consent statement; age
cultures and animals.18–22 The second possible mechanism is 20–60 years; bilateral symptoms of pain and tenderness from
similar to that of NSAIDs and steroids. Controlled laboratory the Achilles tendons that could be aggravated by some type of
trials have revealed that LLLT can reduce inflammation physical activity; willingness to perform the type of physical
through reduction of PGE2 concentrations and inhibition of activity that by experience aggravated Achilles tendon pain;
cyclo-oxygenase 2 in cell cultures.23 24 This effect has also pathological sonographic appearance of tendon thickening
been shown in an animal trial, but to our knowledge no study
has yet confirmed such an anti-inflammatory effect in Abbreviations: LLLT, low level laser therapy; NSAID, non-steroidal anti-
humans.25 Microdialysis is a technique used to assess inflammatory drug; PGE2, prostaglandin E2; RI, resistive index
www.bjsportmed.com
2. Laser therapy for Achilles tendinitis 77
and structural alterations of tendon matrix. Exclusion criteria water. Syringes for both Achilles tendons were then placed in
were: systemic inflammatory disease; previous operations on a syringe pump (CMA/100) and adjusted to give 2 ml/min.
Achilles tendons; pregnancy; mental inability to understand Samples of the harvested fluid were collected every 15 min-
the consequences of participation; NSAID treatment during utes. After a stabilisation period of 60 minutes, baseline
the preceding four weeks; steroidal treatment during the levels were registered for another 60 minutes before laser
preceding six months; monogenic familial hypercholestero- treatment was administered. PGE2 concentrations after
laemia (may cause Achilles tendon xanthomas). treatment were recorded for 105 minutes. PGE2 concentra-
tion in the dialysate was analysed by a high sensitivity
Examination procedure and outcome measures Prostaglandin E2 Enzyme Immunoassay Kit (Electra-box
Each patient was examined by interview about symptom Diagnostica AS, Stockholm, Sweden). The washing, the
characteristics, symptom duration, and specific activities that adding of substrate solutions and stop solutions, and the
caused aggravation of Achilles tendon symptoms. A physical analyses were performed according to the manufacturers’
examination was then performed. After location of the most specifications. For each well, the absorbance was read using a
painful spot identified by finger palpation, pressure pain microplate reader (Spectramax; Molecular Devices,
threshold was measured as the average of three tests with Sunnyvale, California, USA) set to 450 nm, with wavelength
pressure pain algometry. This test was performed by pressing control.
a circular metallic tip of area 1 cm2 with gradually increasing
force to the most painful spot of the tendon. The patient was Intervention
told to respond by saying ‘‘stop’’ when the feeling of pressure LLLT was administered by a GaAs laser with an infrared
changed to pain. Before the experiment, this test was checked wavelength of 904 nm (Irradia AB, Stockholm, Sweden) with
on healthy subjects for test-retest reliability; the intraclass a laser probe consisting of three laser diodes placed long-
correlation coefficient was 0.79 and standard deviation itudinally 9 mm apart. On the laser probe, an A/B switch
0.39 kg/cm2, which is similar to other reliability studies for determined whether active or sham irradiation was given.
pressure pain threshold.32–34 During operation the laser appeared identical for both active
Functional ability was tested by measuring the mean and sham irradiation, because of the invisible nature of the
distance of three repetitions reached in the single leg hop infrared laser beam and the same blinking red diode and
test.35 Ultrasonography (Siemens Sonoline G60) was per- descending time counter. The output of the laser averaged
formed to ensure the exact location of tendon pathology. 10 mW for each diode, which was tested and calibrated
Tendon thickness was measured using calibrated callipers, before and after treatment for every patient by technical staff
and structural alteration of the tendon matrix was described. not otherwise involved in the experiment. The peak power for
Tendon vascularisation was examined by power Doppler. If each laser pulse was 10 W and pulse duration was
possible, peritendinous or intratendinous arterial blood flow 200 nanoseconds (1029 seconds), delivered by a frequency
velocity was also measured, as they can be used to detect of 5000 Hz. The spot area was 0.5 cm2 giving a power density
signs of inflammation through the arterial resistive index (fluence) of 20 mW/cm2. Each patient was treated for
(RI), which is a measure of vasodilatation and inflamma- 180 seconds, and the dose of active treatment was 1.8 J for
tion.36 RI is defined as: (systolic peak velocity minus end each of three points along the Achilles tendons, giving a total
diastolic velocity)/systolic peak velocity. Values of less than 1 of 5.4 J per tendon.
(normal) indicate inflammation.
Microdialysis was performed by first giving a local Blinding and randomisation procedure
anaesthetic injection (xylocaine, 20 mg/ml; AstraZeneca, The trial was designed to achieve randomised concealed
Oslo, Norway) at the insertion site 30 mm cranially to the allocation to groups and double blinding. As patients were
centre of pathology. After four to five minutes, the micro- acting as their own controls, both Achilles tendons were
dialysis membrane (CMA/60, cut off 20 kDa, membrane treated, but only one received active treatment. Which side
length 30 mm, outer diameter 0.6 mm; CMA, Stockholm, should be treated with the laser probe in switch position A or
Sweden) was inserted into the peritendinous tissue parallel B was decided for each patient by drawing one of 10 opaque
to the Achilles tendon. Insertion into the tissue is achieved envelopes containing a written character A or B (five of
with the help of a slit cannula introducer which leaves the
catheter in place when withdrawn. Before withdrawal of the
introducer, the position of the membrane was checked by
PGE2 concentration relative to baseline
ultrasonography. The microdialysis membrane and tubes 1.70
Laser
were then coupled to a syringe containing isotonic 0.9% salt Placebo
1.50
1.30
2.5
Pain pressure threshold (kg/cm2)
Laser 1.10
1.66
2 Placebo
1.45
1.4
0.90
1.5 1.21
1 p = 0.012 0.70
0.5 0.19 0.50
1 2 3 4 5 6 7
0 Time (15 minute intervals)
–0.5 –0.21
Figure 2 Laser effect on inflammation as measured by prostaglandin E2
–1 (PGE2) concentrations in peritendinous tissue. Mean post-treatment PGE2
Before After Change concentrations and their respective 95% confidence intervals relative to
the mean pre-treatment baseline results are shown. Values were
Figure 1 Mean pressure pain thresholds of three recordings from each recorded at seven consecutive 15 minute intervals (total 165 minutes
tendon with their respective 95% confidence intervals grouped by after treatment), and the significant between-groups difference at the last
treatment allocation. time point is indicated by an asterisk.
www.bjsportmed.com
3. 78 Bjordal, Martins-Lopes, Iversen
each). The A/B switch on the laser was then switched to the Single jump hop test
character drawn, and treatment started for the right leg first. Because of the fragile microdialysis membrane and the
Thus the allocation of tendon to groups was concealed from importance of harvesting fluid meticulously, the single hop
patients, therapist, and observer. The code of the A/B switch test could only be performed before and after microdialysis.
positions on the laser probe was only known to the technical Both groups showed a decrease in the single jump hop test
staff who calibrated the laser before and after each patient. after treatment. However, the mean decrease was signifi-
The code was not broken until all treatments and analyses cantly less (p = 0.025) for the laser treated group (10.6 cm
were finished. (95% CI 3.5 to 17.7) than for the placebo group (18.4 cm
(95% CI 12.3 to 24.5)).
Ethical approval
The experiments in this study were performed with the Ultrasound Doppler scanning
approval of, and in accordance with the regulations laid At baseline all 14 tendons exhibited increased peritendinous
down by, the regional ethics committee of Western Norway and intratendinous blood flow when assessed by colour
Doppler in a relaxed position of ankle plantar flexion. At
(no 144/03). Participants gave signed informed consent.
follow up, blood flow measured by colour Doppler seemed to
have decreased in all tendons, but no arbitrary assessment
RESULTS was performed. The decreased flow was thought to be a result
Randomisation procedure of the necessary physical inactivity in the experimental set
Four right side and three left side Achilles tendons were given up.
active treatment. For power Doppler measurements of blood flow, velocity
and RI could only be measured at baseline in eight tendons,
Pressure pain threshold five in the active LLLT group and three in the placebo LLLT
There was a small, but non-significant mean decrease group. The mean RI for these eight tendons indicated a
(20.05 kg/cm2) in the pressure pain threshold from the start small inflammatory reaction, with RI 0.91 (95% CI 0.87
to 0.95) (fig 3). No significant differences between
of the observation period to immediately before treatment.
groups were observed after treatment for any ultrasound
However, after treatment it had increased by 0.19 kg/cm2
measures.
(95% confidence interval (CI) 0.04 to 0.34) in the laser group,
whereas a decrease of 20.21 kg/cm2 (95% CI +0.04 to 20.46)
was recorded for the placebo group from the start to the end Side effects and adverse reactions
the observation period. The mean difference in change was The experiment was well tolerated by all patients. Local
0.40 kg/cm2 (95% CI 0.10 to 0.70) (fig 1). injection of analgesic (xylocaine) and placement of the
microdialysis catheter caused minor transient pain at the
time of insertion. Likewise, the application of the pressure
Inflammatory marker PGE 2 concentrations pain algometer caused increased tenderness in the area of the
In the laser group, a small decrease in PGE2 concentration Achilles tendon, probably partly because of the repeated pain
was seen first one hour after treatment, and then gradually threshold pressure applications and partly because the effect
decreasing from baseline (1.0) to 0.72 (95% CI 0.58 to 0.86) at of the local anaesthetic was tailing off. None of the patients
the last time point 105 minutes after treatment. For the experienced infections or other complications, and they all
placebo group, PGE2 concentrations increased gradually in reported that being bored was a greater problem than the
the period after treatment from baseline to 1.30 (95% CI 1.48 transient pain they experienced.
to 1.12) at the last observation. For the laser group, there was
a significant difference in both the pre-treatment and post- DISCUSSION
treatment means (p = 0.0269) and the difference in change To our knowledge, other physiotherapy methods have failed
between the groups (p = 0.0096) (fig 2). to produce relevant anti-inflammatory effects in the labora-
tory. In this trial, we show that LLLT can suppress
inflammation, as measured by a reduction in the inflamma-
tory marker PGE2. In addition, clinical indices of small,
but significant improvements in pressure pain and single
hop function were observed. The ultrasound measurements
were not suitable for detecting differences at follow up
mainly because the experimental set up, with hours of
physical inactivity, reduces peripheral circulation to a
minimum and impairs ultrasound measurements. Still, our
baseline ultrasound results may be important for
confirming both that pain was actually related to Achilles
pathology and a small degree of inflammation was
possibly present.37 We devised the protocol with prior pain
inducing activity, and the ultrasound measurements of RI
seem to suggest that a small inflammatory reaction had
been induced. Our findings possibly contradict other
claims that inflammation is not present in Achilles tendino-
pathy.28 In our opinion, this is not a true contradiction, but
rather an elaboration in the sense that inflammation may
play a small, but important part in episodes of symptom
aggravation. This question remains to be more thoroughly
Figure 3 Colour Doppler image of a transverse section of Achilles
tendon showing intratendinous blood vessels (right hand frame) and
investigated.
power Doppler (left hand frame) assessment of intratendinous blood flow The small increase in PGE2 concentration seen in both
velocity in systolic peak (26.1 cm/s) and diastolic end (2.8 cm/s), giving active and placebo groups immediately after treatment was
a resistive index of 0.89, indicating minor inflammation. probably caused by a local reaction to the pressure pain
www.bjsportmed.com
4. Laser therapy for Achilles tendinitis 79
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.............. COMMENTARY ..............
32 Smidt N, van der Windt DA, Assendelft WJ, et al. Interobserver
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33 Maquet D, Croisier JL, Demoulin C, et al. Pressure pain thresholds of tender therapy (LLLT) with 904 nm laser reduces the production of
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36 Terslev L, Torp-Pedersen S, Qvistgaard E, et al. Estimation of inflammation by
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38 Fahlstrom M, Jonsson P, Lorentzon R, et al. Chronic Achilles tendon pain raised. Interestingly, this study suggests an inflammatory
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