Christoph Spang

The plantaris tendon in association with mid-portion Achilles tendinosis : tendinosis-like morphological features and presence of a non-neuronal cholinergic system

The plantaris tendon is often neglected in morphological/clinical studies on the lower extremity. There is, however, clinical evidence that the plantaris tendon is involved in cases with Achilles midportion tendinopathy/tendinosis. It is nevertheless unclear if the plantaris tendon exhibits tendinosis-like features in this situation. We therefore investigated the plantaris tendon of patients with midportion Achilles tendinosis when the plantaris tendon was found to be located very close to or invaginated into the Achilles tendon, a situation which very often has been found to be the case. There was a very large number of tenocytes in the tendon tissue and the tenocytes showed abnormal and irregular appearances, exhibiting widened/rounded and wavy appearances, and were frequently lined up in rows. These features are characteristic features in Achilles tendinosis tendons. The tendon cells showed a distinct immunoreaction for the acetylcholine (ACh) -producing enzyme choline acetyltransferase (ChAT). Frequent fibroblasts were found in the loose connective tissue and these cells also showed a marked ChAT immunoreaction. The study shows that the plantaris tendon is morphologically affected in a similar way to the Achilles tendon in cases with midportion Achilles tendinosis and medial pain. The plantaris tendon may accordingly be a co-factor in these cases. The results also favour that there is a local ACh production both within the tendon tissue of the plantaris tendon and in the loose connective tissue. In conclusion, it is evident that plantaris tendons lying invaginated into or very close to the Achilles tendon in cases with midportion Achilles tendinosis show similar tendinosis features, as previously shown for the Achilles tendon itself in these cases.

Achilles tendinopathy—do plantaris tendon removal and Achilles tendon scraping improve tendon structure? A prospective study using ultrasound tissue characterisation

Objectives The plantaris tendon has recently been described as a possible important factor in midportion Achilles tendinopathy. Ultrasound tissue characterisation (UTC) is a method to study tendon structure (matrix integrity). The effect of plantaris tendon removal on Achilles tendon structure was studied using UTC. Design and setting Prospective case series study at one centre. Participants Nine tendons in eight physically active and healthy patients (mean age 39 years) with chronic painful midportion Achilles tendinopathy were included. Preoperative two-dimensional ultrasound and UTC showed midportion Achilles tendinopathy (tendinosis) with medial tendon changes and suspected plantaris tendon involvement. Patients with previous operations to the Achilles tendon were excluded. Interventions Operative treatment consisted of excision of the plantaris tendon and scraping of the ventromedial surface of the Achilles tendon under a local anaesthetic. Primary and secondary outcome measures UTC examination and clinical scoring with the VISA-A questionnaire were performed preoperatively and 6 months postoperatively. Results At 6 months follow-up, UTC demonstrated a statistically significant (t=5.40, p<0.001) increase in the mean organised matrix (echo-type I+II) and a decrease in the mean disorganised matrix (echo-type III+IV). Seven out of eight patients were satisfied, and the VISA-A score had increased significantly (p<0.001) from 56.8 (range 34–73) preoperatively to 93.3 (range 87–100) postoperatively. Conclusions Excision of the plantaris tendon and scraping of the ventromedial Achilles tendon in chronic midportion tendinopathy seem to have the potential to improve tendon structure and reduce tendon pain. Studies on a larger group of patients and with a longer follow-up period are needed.

Unilateral surgical treatment for patients with midportion Achilles tendinopathy may result in bilateral recovery

Background Bilateral midportion Achilles tendinopathy/tendinosis is not unusual, and treatment of both sides is often carried out. Experiments in animals suggest of the potential involvement of central neuronal mechanisms in Achilles tendinosis. Objectives To evaluate the outcome of surgery for Achilles tendinopathy. Methods This observational study included 13 patients (7 men and 6 women, mean age 53 years) with a long duration (6–120 months) of chronic painful bilateral midportion Achilles tendinopathy. The most painful side at the time for investigation was selected to be operated on first. Treatment was ultrasound-guided and Doppler-guided scraping procedure outside the ventral part of the tendon under local anaesthetic. The patients started walking on the first day after surgery. Follow-ups were conducted and the primary outcome was pain by visual analogue scale. In an additional part of the study, specimens from Achilles and plantaris tendons in three patients with bilateral Achilles tendinosis were examined. Results Short-term follow-ups showed postoperative improvement on the non-operated side as well as the operated side in 11 of 13 patients. Final follow-up after 37 (mean) months showed significant pain relief and patient satisfaction on both sides for these 11 patients. In 2 of 13 patients operation on the other, initially non-operated side, was instituted due to persisting pain. Morphologically, it was found that there were similar morphological effects, and immunohistochemical patterns of enzyme involved in signal substance production, bilaterally. Conclusion Unilateral treatment with a scraping operation can have benefits contralaterally; the clinical implication is that unilateral surgery may be a logical first treatment in cases of bilateral Achilles tendinopathy.

VGluT2 and NMDAR1 Expression in Cells in the Inflammatory Infiltrates in Experimentally Induced Myositis: Evidence of Local Glutamate Signaling Suggests Autocrine/Paracrine Effects in an Overuse Injury Model

It is not known whether a glutamate signaling system is involved in muscle inflammation (myositis). In the present study, we examined this question in the soleus muscle in a laboratory model of myositis resulting from repetitive overuse induced by electrical stimulation and injection of pro-inflammatory substances. Sections of rabbit soleus muscle with an induced myositis, i.e., exhibiting infiltration of inflammatory cells, were examined immunohistochemically using antibodies against vesicular glutamate transporter VGluT2 and the glutamate receptor NMDAR1. In situ hybridization for demonstration of VGluT2 mRNA was also performed. Specific reactions for both VGluT2 and NMDAR1 could be observed immunohistochemically in the same cells. In situ hybridization demonstrated the occurrence of VGluT2 mRNA in the cells. Double staining showed that the VGluT2 reactions were detectable in cells marked with T cell/neutrophil marker and in cells expressing eosinophil peroxidase. These data suggest the occurrence of previously unknown glutamate-mediated autocrine/paracrine effects within the inflammatory infiltrates during the development of muscle inflammation.

The plantaris tendon: a narrative review focusing on anatomical features and clinical importance

In recent years, the plantaris tendon has been implicated in the development of chronic painful mid-portion Achilles tendinopathy. In some cases, a thickened plantaris tendon is closely associated with the Achilles tendon, and surgical excision of the plantaris tendon has been reported to be curative in patients who have not derived benefit following conservative treatment and surgical interventions. The aim of this review is to outline the basic aspects of, and the recent research findings, related to the plantaris tendon, covering anatomical and clinical studies including those dealing with histology, imaging and treatment. Cite this article: Bone Joint J 2016;98-B:1312-19.

Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part I: biology, biomechanics, anatomy and an exercise-based approach

Chronic tendinopathies represent a major problem in the clinical practice of sports orthopaedic surgeons, sports doctors and other health professionals involved in the treatment of athletes and patients that perform repetitive actions. The lack of consensus relative to the diagnostic tools and treatment modalities represents a management dilemma for these professionals. With this review, the purpose of the ESSKA Basic Science Committee is to establish guidelines for understanding, diagnosing and treating this complex pathology.

The tenocyte phenotype of human primary tendon cells in vitro is reduced by glucocorticoids.

BackgroundThe use of corticosteroids (e.g., dexamethasone) as treatment for tendinopathy has recently been questioned as higher risks for ruptures have been observed clinically. In vitro studies have reported that dexamethasone exposed tendon cells, tenocytes, show reduced cell viability and collagen production. Little is known about the effect of dexamethasone on the characteristics of tenocytes. Furthermore, there are uncertainties about the existence of apoptosis and if the reduction of collagen affects all collagen subtypes.MethodsWe evaluated these aspects by exposing primary tendon cells to dexamethasone (Dex) in concentrations ranging from 1 to 1000 nM. Gene expression of the specific tenocyte markers scleraxis (Scx) and tenomodulin (Tnmd) and markers for other mesenchymal lineages, such as bone (Alpl, Ocn), cartilage (Acan, Sox9) and fat (Cebpα, Pparg) was measured via qPCR. Cell viability and proliferation was calculated using a MTS Assay. Cell death was measured by LDH assay and cleaved caspase-3 using Western Blot. Gene expression of collagen subtypes Col1, Col3 and Col14 was analyzed using qPCR.ResultsStimulation with Dex decreased cell viability and LDH levels. Dex also induced a significant reduction of Scx gene expression and a marked loss of fibroblast like cell shape. The mRNA for all examined collagen subtypes was found to be down-regulated. Among non-tendinous genes only Pparg was significantly increased, whereas Acan, Alpl and Sox9 were reduced.ConclusionsThese results indicate a Dex induced phenotype drift of the tenocytes by reducing scleraxis expression. Reduction of several collagen subtypes, but not cell death, seems to be a feature of Dex induced tissue degeneration.

Glutamate signaling through the NMDA receptor reduces the expression of scleraxis in plantaris tendon derived cells

BackgroundA body of evidence demonstrating changes to the glutaminergic system in tendinopathy has recently emerged. This hypothesis was further tested by studying the effects of glutamate on the tenocyte phenotype, and the impact of loading and exposure to glucocorticoids on the glutamate signaling machinery.MethodsPlantaris tendon tissue and cultured plantaris tendon derived cells were immunohisto-/cytochemically stained for glutamate, N-Methyl-D-Aspartate receptor 1 (NMDAR1) and vesicular glutamate transporter 2 (VGluT2). Primary cells were exposed to glutamate or receptor agonist NMDA. Cell death/viability was measured via LDH/MTS assays, and Western blot for cleaved caspase 3 (c-caspase 3) and cleaved poly (ADP-ribose) polymerase (c-PARP). Scleraxis mRNA (Scx)/protein(SCX) were analyzed by qPCR and Western blot, respectively. A FlexCell system was used to apply cyclic strain. The effect of glucocorticoids was studies by adding dexamethasone (Dex). The mRNA of the glutamate synthesizing enzymes Got1 and Gls, and NMDAR1 protein were measured. Levels of free glutamate were determined by a colorimetric assay.ResultsImmunoreactions for glutamate, VGluT2, and NMDAR1 were found in tenocytes and peritendinous cells in tissue sections and in cultured cells. Cell death was induced by high concentrations of glutamate but not by NMDA. Scleraxis mRNA/protein was down-regulated in response to NMDA/glutamate stimulation. Cyclic strain increased, and Dex decreased, Gls and Got1 mRNA expression. Free glutamate levels were lower after Dex exposure.ConclusionsIn conclusion, NMDA receptor stimulation leads to a reduction of scleraxis expression that may be involved in a change of phenotype in tendon cells. Glutamate synthesis is increased in tendon cells in response to strain and decreased by glucocorticoid stimulation. This implies that locally produced glutamate could be involved in the tissue changes observed in tendinopathy.

Choline acetyltransferase and the nicotinic acetylcholine receptor AChRα7 in experimental myositis.

It is not known to what extent a non-neuronal cholinergic system is involved in myositis (muscle inflammation) evoked by marked muscle overuse. Therefore, in the present study, a recently established rabbit myositis model was used and the expression patterns of ChAT and nicotinic acetylcholine receptor AChRα7 (α7nAChR) were evaluated. Immunohistochemistry and in situ hybridization were used. The model leads to myositis including occurrence of muscle fiber necrosis. It was found that the infiltrating white blood cells as well the walls of small blood vessels exhibited immunoreactivity for both ChAT and α7nAChR. There was also pronounced immunoreactivity for these in the white blood cells that had coalesced within the necrotic muscle fibers. The findings show that there is a presence of a non-neuronal cholinergic system in the situation of muscle inflammation. Cholinergic effects may be highly involved in the inflammation-modifying events that occur in muscle overuse.

STUDIES ON ACHILLES TENDINOSIS: BILATERAL RECOVERY AFTER UNILATERAL SURGERY, AND SIMILAR HISTOPATHOLOGICAL APPEARANCES BILATERALLY

It is frequently observed that midportion Achilles tendinopathy/tendinosis occurs bilaterally. With this as a background, the outcome of unilateral operations was evaluated in 13 patients (seven males and six females) with chronic painful bilateral midportion Achilles tendinopathy (tendinosis) (symptom duration: 6–12 months). Prolonged periods of rest did not have an effect. As surgical treatment, an ultrasound and Doppler-guided scraping procedure outside the ventral part of the tendon was performed in local anaesthesia, a method that recently has been found to be successful for patients with Achilles tendinosis. Surgical treatment was performed only on one side, the other side being left untreated. The patients started walking on the first day after surgery, and were followed over time. In an additional part of the study, specimens from Achilles and plantaris tendons in 3 patients with bilateral Achilles tendinosis were examined. Follow-ups showed postoperative improvement also on the non-operated side in 11/13 patients, and a final follow up after 37 (mean) months showed significant pain relief and patient satisfaction on both sides for these 11 patients. In 2/13 patients, operation on the other, initially non-operated side, was needed. Morphologically, it was found that there were similar morphological characteristics and similar immunohistochemical patterns concerning enzymes involved in signal substance production bilaterally, the microscopic findings being in line with previous information from tendinosis tendons. It can be concluded that the structural affections are similar on both sides in bilateral Achilles tendinosis. The study showed that unilateral operative treatment can also have benefits contra-laterally. A hypothesis is that unilateral influences on the sensory innervation in the peritendinous tissue in response to the scraping operation have secondary effects contralaterally, that is, influences on the pattern of primary-afferent activation on one side can have effects contra-laterally. The interpretation concerning a presumable cross-talk between right and left sides are in line with the results of recent experimental studies in animals showing that tendinosis-like features occur bilaterally in the Achilles tendons in response to unilateral overuse, suggesting that there is an involvement of central neuronal mechanisms. The observations of bilateral effects in response to unilateral treatment have clinical implications.