Anti-Inflammatory Effects of Low-Level Light Emitting Diode Therapy on Achilles Tendinitis in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Low-level laser therapy in collagenase-induced Achilles tendinitis in rats: Analyses of biochemical and biomechanical aspects

NSAIDs are widely prescribed and used over the years to treat tendon injuries despite its well-known long-term side effects. In the last years several animal and human trials have shown that low-level laser therapy (LLLT) presents modulatory effects on inflammatory markers, however the mechanisms involved are not fully understood. The aim of this study was to evaluate the short-term effects of LLLT or sodium diclofenac treatments on biochemical markers and biomechanical properties of inflamed Achilles tendons. Wistar rats Achilles tendons (n?=?6/group) were injected with saline (control) or collagenase at peritendinous area of Achilles tendons. After 1?h animals were treated with two different doses of LLLT (810?nm, 1 and 3?J) at the sites of the injections, or with intramuscular sodium diclofenac. Regarding biochemical analyses, LLLT significantly decreased (p?<?0.05) COX-2, TNF-a, MMP-3, MMP-9, and MMP-13 gene expression, as well as prostaglandin E2 (PGE2) production when compared to collagenase group. Interestingly, diclofenac treatment only decreased PGE2 levels. Biomechanical properties were preserved in the laser-treated groups when compared to collagenase and diclofenac groups. We conclude that LLLT was able to reduce tendon inflammation and to preserve tendon resistance and elasticity. (c) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:19451951, 2012

Anisotropy of spin relaxation of water protons in cartilage and tendon

Transverse spin relaxation rates of water protons in articular cartilage and tendon depend on the orientation of the tissue relative to the applied static magnetic field. This complicates the interpretation of magnetic resonance images of these tissues. At the same time, relaxation data can provide information about their organisation and microstructure. We present a theoretical analysis of the anisotropy of spin relaxation of water protons observed in fully hydrated cartilage. We demonstrate that the anisotropy of transverse relaxation is due almost entirely to intramolecular dipolar coupling modulated by a specific mode of slow molecular motion: the diffusion of water molecules in the hydration shell of a collagen fibre around the fibre, such that the molecular director remains perpendicular to the fibre. The theoretical anisotropy arising from this mechanism follows the “magic-angle” dependence observed in magnetic-resonance measurements of cartilage and tendon and is in good agreement with the available experimental results. We discuss the implications of the theoretical findings for MRI of ordered collagenous tissues.

The time course of in vivo recovery of transverse strain in high-stress tendons following exercise

Objective To evaluate the time course of the recovery of transverse strain in the Achilles and patellar tendon following a bout of resistance exercise. Methods Seventeen healthy adults underwent sonographic examination of the right patellar (n=9) and Achilles (n=8) tendons immediately prior to and following 90 repetitions of weight-bearing quadriceps and gastrocnemius-resistance exercise performed against an effective resistance of 175% and 250% body weight, respectively. Sagittal tendon thickness was determined 20 mm from the enthesis and transverse strain, as defined by the stretch ratio, was repeatedly monitored over a 24 h recovery period. Results Resistance exercise resulted in an immediate decrease in Achilles (t7=10.6, p<0.01) and patellar (t8=8.9, p<0.01) tendon thickness, resulting in an average transverse stretch ratio of 0.86±0.04 and 0.82±0.05, which was not significantly different between tendons. The magnitude of the immediate transverse strain response, however, was reduced with advancing age (r=0.63, p<0.01). Recovery in transverse strain was prolonged compared with the duration of loading and exponential in nature. The average primary recovery time was not significantly different between the Achilles (6.5±3.2 h) and patellar (7.1±3.2 h) tendons. Body weight accounted for 62% and 64% of the variation in recovery time, respectively. Conclusions Despite structural and biochemical differences between the Achilles and patellar tendon, the mechanisms underlying transverse creep recovery in vivo appear similar and are highly time dependent. These novel findings have important implications concerning the time required for the mechanical recovery of high-stress tendons following an acute bout of exercise.

How much is enough? The effect of exercise repetition on the force frequency characteristics of eccentric exercise used for tendinopathy rehabilitation

Introduction: Eccentric exercise (EE) is a commonly used treatment for Achilles tendinopathy. While vibrations in the 8–12 Hz frequency range generated during eccentric muscle actions have been put forward as a potential mechanism for the beneficial effect of EE, optimal loading parameters required to expedite recovery are currently unknown. Alfredson's original protocol employed 90 repetitions of eccentric loading, however abbreviated protocols consisting of fewer repetitions (typically 45) have been developed, albeit with less beneficial effect. Given that 8–12 Hz vibrations generated during isometric muscle actions have been previously shown to increase with fatigue, this research evaluated the effect of exercise repetition on motor output vibrations generated during EE by investigating the frequency characteristics of ground reaction force (GRF) recorded throughout the 90 repetitions of Alfredson's protocol. Methods: Nine healthy adult males performed six sets (15 repetitions per set) of eccentric ankle exercise. GRF was recorded at a frequency of 1000 Hz throughout the exercise protocol. The frequency power spectrum of the resultant GRF was calculated and normalized to total power. Relative spectral power was summed over 1 Hz widows within the frequency rage 7.5–11.5 Hz. The effect of each additional exercise set (15 repetitions) on the relative power within each widow was investigated using a general linear modelling approach. Results: The magnitude of peak relative power within the 7.5–11.5 Hz bandwidth increased across the six exercise sets from 0.03 in exercise set one to 0.12 in exercise set six (P < 0.05). Following the 4th set of exercise the frequency at which peak relative power occurred shifted from 9 to 10 Hz. Discussion: This study has demonstrated that successive repetitions of eccentric loading over six exercise sets results in an increase in the amplitude of motor output vibrations in the 7.5–11.5 Hz bandwidth, with an increase in the frequency of these vibrations occurring after the 4th set (60th repetition). These findings are consistent with findings from previous studies of muscle fatigue. Assuming that the magnitude and frequency of these vibrations represent important stimuli for tendon remodelling as hypothesized within the literature, the findings of this study question the role of abbreviated EE protocols and raise the question; can EE protocols for tendinopathy be optimized by performing eccentric loading to fatigue?

Reproducibility and clinical utility of tendon palpation to detect patellar tendinopathy in young basketball players

Background—Palpation is an important clinical test for jumper's knee. Objectives—To (a) test the reproducibility of palpation tenderness, (b) evaluate the sensitivity and specificity of palpation in subjects with clinical symptoms of jumper's knee, and (c) determine whether tenderness to palpation may serve as a useful screening test for patellar tendinopathy. The yardstick for diagnosis of patellar tendinopathy was ultrasonographic abnormality. Methods—In 326 junior symptomatic and asymptomatic athletes' tendons, palpation was performed by a single examiner before ultrasonographic examination by a certified ultrasound radiologist. In 58 tendons, palpation was performed twice to test reliability. Tenderness to palpation was scored on a scale from 0 to 3 where 0 represented no pain, and 1, 2, and 3 represented mild, moderate, and severe tenderness respectively. Results—Patellar tendon palpation was a reliable examination for a single examiner (Pearson r = 0.82). In symptomatic tendons, the positive predictive value of palpation was 68%. As a screening examination in asymptomatic subjects, the positive predictive value of tendon palpation was 36–38%. Moderate and severe palpation tenderness were better predictors of ultrasonographic tendon pathology than absent or mild tenderness (p<0.001). Tender and symptomatic tendons were more likely to have ultrasound abnormality than tenderness alone (p<0.01). Conclusions—In this age group, palpation is a reliable test but it is not cost effective in detecting patellar tendinopathy in a preparticipation examination. In symptomatic tendons, palpation is a moderately sensitive but not specific test. Mild tenderness in the patellar tendons in asymptomatic jumping athletes should be considered normal.

Patellar tendon ultrasonography in asymptomatic active athletes reveals hypoechoic regions : a study of 320 tendons

OBJECTIVE: To compare patellar tendon sonographic findings in active, currently asymptomatic, elite athletes with those in nonathletic controls. DESIGN: Cross-sectional cohort study with convenience control sample. SETTING: The Victorian Institute of Sport Tendon Study Group, an institutional elite athlete study group in Australia. PATIENTS AND PARTICIPANTS: Two hundred elite male and female athletes from the sports of basketball, cricket, netball, and Australian rules football. Forty athletes who had current symptoms of jumper's knee were excluded from analysis, leaving 320 subject tendons in athletes who were currently asymptomatic. Twenty-seven nonathletic individuals served as controls. MAIN OUTCOME MEASURE: Sonographic patellar tendon appearance. We measured the dimensions of subject tendons and noted the presence or absence of hypoechoic regions and tendon calcification. Dimensions of hypoechoic regions were measured, and approximate cross-sectional areas were calculated. Chi-squared analysis was used to test the prevalence of hypoechoic regions in subjects and controls and men and women. RESULTS: In currently asymptomatic subjects, hypoechoic regions were more prevalent in athlete tendons (22%) than in controls (4%), in male subject tendons (30%) than in female subjects (14%), and in basketball players (32%) than in other athletes (9%) (all p < 0.01). Bilateral tendon abnormalities were equally prevalent in men and women but more prevalent in basketball players (15%) than in other athletes (3%) (p < 0.05). Sonographic hypoechoic regions were present in 35 of 250 (14%) patellar tendons in athletes who had never had anterior knee pain. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas were present in asymptomatic patellar tendons of a proportion of elite athletes but rarely present in controls. This has implications for clinicians managing athletes with anterior knee pain.

Asymptomatic hypoechoic regions on patellar tendon ultrasound : a 4-year clinical and ultrasound followup of 46 tendons

Patellar tendon ultrasound appearance is commonly used in clinical practice to diagnose patellar tendinopathy and guide management. Using a longitudinal study design we examined whether or not the presence of a hypoechoic ultrasonographic lesion in an asymptomatic patellar tendon conferred a risk for developing jumper's knee compared with a tendon that was ultrasonographically normal. Ultrasonographic, symptomatic and anthropometric assessment was completed at baseline and followup. Magnetic resonance imaging was performed on four tendons that resolved ultrasonographically in the study period. Forty-six patellar tendons were followed over 47 ± 11.8 months. Eighteen tendons were hypoechoic at baseline and 28 were ultrasonographically normal. Five tendons resolved ultrasonographically in the study period. Magnetic resonance imaging in four of these tendons was normal. Seven normal patellar tendons at baseline developed a hypoechoic area but only two became symptomatic. Analysis of ultrasonography at baseline and clinical outcome with Fisher's exact test shows there is no association between baseline ultrasound changes and symptoms at followup. In this study there is no statistically significant relationship between ultrasonographic patellar tendon abnormalities and clinical outcome in elite male athletes. Management of jumper's knee should not be solely based on ultrasonographic appearance; clinical assessment remains the cornerstone of appropriate management.

A poly(lactic-co-glycolic acid) knitted scaffold for tendon tissue engineering: an in vitro and in vivo study

We have designed a composite scaffold for potential use in tendon or ligament tissue engineering. The composite scaffold was made of a cellularized alginate gel that encapsulated a knitted structure. Our hypothesis was that the alginate would act as a cell carrier and deliver cells to the injury site while the knitted structure would provide mechanical strength to the composite construct. The mechanical behaviour and the degradation profile of the poly(lactic-co-glycolic acid) knitted scaffolds were evaluated. We found that our scaffolds had an elastic modulus of 750 MPa and that they lost their physical integrity within 7 weeks of in vitro incubation. Autologous rabbit mesenchymal stem cell seeded composite scaffolds were implanted in a 1-cm-long defect created in the rabbit tendon, and the biomechanical properties and the morphology of the regenerated tissues were evaluated after 13 weeks. The regenerated tendons presented higher normalized elastic modulus of (60%) when compared with naturally healed tendons (40%). The histological study showed a higher cell density and vascularization in the regenerated tendons.

Recovery of transverse strain in high–stress tendons following exercise

Background. This study evaluated the time course of recovery of transverse strain in the Achilles and patellar tendons following a bout of resistance exercise. Methods. Seventeen healthy adults underwent sonographic examination of the right patellar (n = 9) or Achilles (n = 8) tendons immediately prior to and following 90 repetitions of weight–bearing exercise. Quadriceps and gastrocnemius exercise were performed against an effective resistance of 175% and 250% body weight, respectively. Sagittal tendon thickness was determined 20 mm from the tendon enthesis and transverse strain was repeatedly monitored over a 24 hour recovery period. Results. Resistance exercise resulted in an immediate decrease in Achilles (t7 = 10.6, P<.01) and patellar (t8 = 8.9, P<.01) tendon thickness, resulting in an average transverse strain of 0.14 ± 0.04 and 0.18 ± 0.05. While the average strain was not significantly different between tendons, older age was associated with a reduced transverse strain response (r=0.63, P<.01). Recovery of transverse strain, in contrast, was prolonged compared with the duration of loading and exponential in nature. The mean primary recovery time was not significantly different between Achilles (6.5 ± 3.2 hours) and patellar (7.1 ± 3.2 hours) tendons and body weight accounted for 62% and 64% of the variation in recovery time, respectively. Discussion. Despite structural and biochemical differences between the Achilles and patellar tendons [1], the mechanisms underlying transverse creep–recovery in vivo appear similar and are highly time dependent. Primary recovery required about 7 hours in healthy tendons, with full recovery requiring up to 24 hours. These in vivo recovery times are similar to those reported for axial creep recovery of the vertebral disc in vitro [2], and may be used clinically to guide physical activity to rest ratios in healthy adults. Optimal ratios for high–stress tendons in clinical populations, however, remain unknown and require further attention in light of the knowledge gained in this study.

Mesenchymal stem cell therapies for bone and tendon conditions

Bone, tendon, and cartilage are highly specialized musculoskeletal connective tissues that are subject to injury and degeneration. These tissues have relatively poor healing capabilities, and coupled with their variable response to established medical treatments, produce significant morbidity. Mesenchymal stem cells (MSCs) are capable of regenerating skeletal tissues and therefore offer great promise in the treatment of connective tissue pathologies. Adult MSCs are multipotent cells that possess the properties of proliferation and differentiation into all connective tissues. Furthermore, they can be gene modified to secrete growth factors and utilized in connective tissue engineering. Potential MSC-based therapies for bone and tendon conditions are reviewed in this chapter.

A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury

Collagen synthesis inhibition potentially can reduce adhesion formation after tendon injury but also may affect cutaneous wound healing. We hypothesized that a novel orally administered collagen synthesis inhibitor (CPHI-I) would substantially reduce flexor tendon adhesions after injury, without any clinically important effect on cutaneous wound healing. The experiments were performed in a rat model with an in-continuity crush injury model in the rat hindfoot flexor tendon to provoke adhesion formation. Assays of dermal collagen production and the rate of healing of an excised wound were performed to assess cutaneous wound healing. Animals in the treatment groups received CPHI-I for 1, 2, or 6 weeks and were assessed at either 2 or 6 weeks. The work of flexion in the injured digit was reduced in the CPHI-I-treated animals compared with control animals, (0.188 J versus 0.0307 J at 2 weeks, and 0.0231 J versus 0.0331 J at 6 weeks) The cutaneous wound healing rate was similar in all animals, but dermal collagen synthesis was reduced in the treated animals. The CPHI-I seems to reduce tendon adhesion, and although collagen synthesis was reduced in cutaneous wounds, CPHI-I did not retard wound healing.

Tendinopathy alters cumulative transverse strain in the patellar tendon postexercise.

Introduction This research evaluated the effect of tendinopathy on the cumulative transverse strain response of the patellar tendon to a bout of resistive quadriceps exercise. Methods Nine adults with unilateral patellar tendinopathy (age 18.2±0.7 years, height 1.92±0.06 m and weight 76.8±6.8 kg) and ten healthy adults free of knee pain (age 17.8±0.8 years, height 1.83±0.05 m and weight 73.2±7.6 kg) underwent standardised sagittal sonograms (7.2–14 MHz linear–array transducer) of both patellar tendons immediately prior and following 45 repetitions of a double–leg decline–squat exercise performed against a resistance of 145% bodyweight. Tendon thickness was determined 5–mm and 25–mm distal to the patellar pole. Transverse Hencky strain was calculated as the natural log of the ratio of post– to pre–exercise tendon thickness and expressed as a percentage. Measures of tendon echogenicity were calculated within the superficial and deep aspects of each tendon site from gray–scale profiles. Intratendinous microvessels were evaluated using power Doppler ultrasound. Results The cumulative transverse strain response to exercise in symptomatic tendinopathy was significantly lower than that of asymptomatic and healthy tendon (P<.05). There was also a significant reduction (57%) in the area of microvascularity immediately following exercise (P=.05), which was positively correlated (r=0.93, P<.05) with VISA-P score. Conclusions This study is the first to show that patellar tendinopathy is associated with an altered morphological and mechanical response of the tendon to exercise, which is manifest by a reduction in cumulative transverse strain and microvascularity, when present. Research directed toward identifying factors that influence the acute microvascular and transverse strain response of the patellar tendon to exercise in the various stages of tendinopathy is warranted.

Long-term follow-up of flexor digitorum longus transfer and calcaneal osteotomy for stage II posterior tibial tendon dysfunction

Flexor digitorum longus transfer and medial displacement alcaneal osteotomy is a wellrecognised form of treatment or stage II posterior tibial tendon dysfunction. Although excellent short- and medium-term results have been reported, the long-term outcome is unknown. We reviewed the clinical outcome of 31 patients with a symptomatic flexible flatfoot deformity who underwent this procedure between 1994 and 1996. There were 21 women and ten men with a mean age of 54.3 years (42 to 70). The mean follow-up was 15.2 years (11.4 to 16.5). All scores improved significantly (p < 0.001). The mean American Orthopedic Foot and Ankle Society (AOFAS) score improved from 48.4 pre-operatively to 90.3 (54 to 100) at the final follow-up. The mean pain component improved from 12.3 to 35.2 (20 to 40). The mean function score improved from 35.2 to 45.6 (30 to 50). The mean visual analogue score for pain improved from 7.3 to 1.3 (0 to 6). The mean Short Form-36 physical component score was 40.6 (SD 8.9), and this showed a significant correlation with the mean AOFAS score (r = 0.68, p = 0.005). A total of 27 patients (87%) were pain free and functioning well at the final follow-up. We believe that flexor digitorum longus transfer and calcaneal osteotomy provides long-term pain relief and satisfactory function in the treatment of stage II posterior tibial tendon dysfunction.