**5.2. Intra-articular injections**

All the principles that led the application of the ESWT since 1995 have been revised in a recent review, that has established new ones. The recommended energy limit should be beneath 0.28 mJ/mmq, above which necrotic effects prevail; ESWT is performed without anesthesia, even

The regenerative effect of ESWT is the consequence of the activation of gene expression for growth factors or cytokines and fibroblast proliferation. Mechanical stimulation is converted by tendon tissue in enhancement of TGF-β1 gene expression and increase of collagen I and collagen III [93]. The phenomenon of mechanosensing is particularly clear in bone tissue, due to its structure and physiology: it acts like a piezoelectric. After ESWT exposure, bone shows: osteogenic differentiation of mesenchymal stem cells [94]; expression of nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) that lead to neoangiogenesis and accelerate tissue regeneration and healing [95]; bone regeneration, starting from periosteum stimulation [96];

In addition, the increase in NOS appears to be involved in another signaling pathway leading to the reduction of pro-inflammatory factors. It has been seen that NOS exerts an inhibitory action on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), hence the role in production of proinflammatory cytokine and leukocytes recruitment, generating pain

Other mechanism is the production of NO and VEGF resulting in neoangiogenesis (**Figure 6**) that improves blood supply promoting tissue repairing and wash-out of algogenic and nox-

ESWT intervene in pain modulation also by release of endogenous analgesic sustances P and calcitonine gene-related peptide (CGRP) and according to the gate control [100]. About the gate control, Saggini et al. [101], claim that a hyperstimulation-like shock waves, activate the descending inhibitory system, blocking following nociceptive stimuli in the posterior column of the spinal cord. In addition, ESWT modify substances P and CGRP levels, damaging peripheral small unmyelinated fibers, responsible of immediate release of the algogenic peptide. All these mechanisms make ESWT suitable to treat various musculoskeletal disorders,

ESWT has proved to be a valid option in the treatment of calcifying tendinitis of the shoulder. A study based on a meta-analysis showed the power of ESWT to intervene in case of calcific

such as calcific tendonitis, epicondylitis, osteoarthritis and long bone fracture [102].

**Figure 6.** Coronary neovascularization after 4 weeks of shock wave therapy.

on larger areas; their application also on open growth plates seems to be safe [92].

direct stimulation of osteoblasts and indirect reduction of osteoclasts activity [97].

and phlogosis, are blocked [98].

ious substances [99].

222 Advances in Shoulder Surgery

Intra-articular drug administration offers several advantages: increased bioavailability, reduced systemic effects and fewer side effects. Moreover, most joints can be accessed accurately, especially under ultrasound guidance [107].

Intra-articular injections into the glenohumeral joint are commonly performed to treat different conditions affecting this articulation, such as osteoarthritis, adhesive capsulitis and rheumatoid arthritis. Despite the widespread use of this treatment, there are no standard criteria for their performance [26].

With regard to this type of therapy applied to the treatment of shoulder pain, two substances are used: corticosteroids and hyaluronic acid [108]. The pharmacological properties of corticosteroids are well known, in accordance with them, this procedure is recommended in the acute phase. The risks associated with corticosteroid injection are limited if performed by experienced hands and in patients eligible for such procedure. Injection should be avoided in patients with septic arthritis, bacteremia and in immunocompromised patients [109].

The main purpose in treating the frozen shoulder is to reduce the loss of function and to give relief to pain that significantly limits movement. In the case of adhesive capsulitis, intraarticular administration of corticosteroids is generally associated with conventional physical therapy. A systematic review of 25 studies from 1947 to present, compares infiltrations with manipulation under anesthesia, physical therapy and distension of the joint capsule. In all cases it is clear that intra-articular administration of corticosteroids improves and accelerate patients' healing. Long-term results about conventional therapies versus corticosteroids are comparable; due to understandable considering that adhesive capsulitis is a self-limiting pathology [110].

avoids the superior migration of the humeral head and the scapular instability, two condi-

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A deficit in neuromuscular control may cause abnormalities in the rotator cuff and scapulathoracic muscles. It has been postulated that proprioception can modulate the sensitivity of

Exercises that specifically generate higher level of activation of the rotator cuff, lower trapezius or serratus anterior, are open-chain exercises included full can, side lying external rotation, diagonal exercise and prone full can at 100° of abduction [121]. While the closed-chain exercises facilitate the co-contraction of shoulder muscles as well as strengthen the serratus

The brain guides motion tasks by interacting with external signals and proprioceptive stimuli. Therefore, stimuli integration takes place here and the center that generates an answer to

A possible way to reach this aim is the Multi-Joint System® (MJS), a system consisting of a multi-articulated arm run by the patient on the three planes of space (**Figure 8**). The patient receives feedback from a computer system connected to the robot arm and adjusts his movements, following predefined trajectories. In this way, the patient learns to perform all the

muscle spindles and help subjects to pay more attention to joint position [120].

tions that occur in the impingement syndrome.

anterior [122].

them can be re-edited.

**Figure 8.** Multi-Joint System®.

Another possible application of corticosteroids involves infiltration within the subacromial bursa; this method (**Figure 7**) is particularly useful in those cases of acute painful bursitis, in combination with other therapies aimed at treating the underlying cause.

Besides the corticosteroids, whose action and effectiveness are widely dealt in literature, the use of the viscosupplementation with hyaluronic acid is becoming increasingly widespread [111]. Hyaluronic acid acts through different mechanisms when injected into the joint. It is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial and neural tissues, is capable of retaining water and this contributes to cell adhesion, proliferation and migration. High local concentrations cause the release of growth factors, accelerating the tissue repair process [112]. The viscosupplementation is a way to restore rheological properties of the synovial fluid, enhancing viscoelastic properties of synovial fluid protecting cartilage from mechanical stress and reducing pain [113, 114].

In the tendinitis involving the rotator cuff, viscosupplementation, not only protects the joint surface, but also restores the homeostasis of the chondrocytes [115]. The hypothesis that hyaluronic acid also acts on pain modulation has been investigated and Mitsui et al. [116] demonstrate that hyaluronic acid inhibits not only expression of mRNA for proinflammatory cytokines, such as IL-1b, IL-6 and TNF-a, but also COX-2/PGE2 (Prostaglandin E2) production via CD44 in IL-1-stimulated subacromial-synovium fibroblasts. CD44 is also present on synoviocytes, so it is a target for pain reduction. The restoration of the viscoelastic barrier around the nociceptive afferent fibers, reduces pain, hindering interaction with nociceptive stimuli [117].

#### **5.3. Rehabilitation**

The rehabilitation program should always start from clinical evaluation, focusing on the status of functional deficiency, the range of motion and the pain elicited during evaluation [118]. The aim is to ensure long-term results in joint mobility, to reduce stiffness and improve function [119].

Maintaining the range of movements is essential to prevent adhesion and decrease impingement. To intervene on the strength of the rotator cuff muscles and on the scapula stabilizing muscles (anterior serratus, rhomboids, latissimus dorsi and trapezium) and the deltoid,

**Figure 7.** Sequence of subacromial bursa infiltration.

avoids the superior migration of the humeral head and the scapular instability, two conditions that occur in the impingement syndrome.

A deficit in neuromuscular control may cause abnormalities in the rotator cuff and scapulathoracic muscles. It has been postulated that proprioception can modulate the sensitivity of muscle spindles and help subjects to pay more attention to joint position [120].

Exercises that specifically generate higher level of activation of the rotator cuff, lower trapezius or serratus anterior, are open-chain exercises included full can, side lying external rotation, diagonal exercise and prone full can at 100° of abduction [121]. While the closed-chain exercises facilitate the co-contraction of shoulder muscles as well as strengthen the serratus anterior [122].

The brain guides motion tasks by interacting with external signals and proprioceptive stimuli. Therefore, stimuli integration takes place here and the center that generates an answer to them can be re-edited.

A possible way to reach this aim is the Multi-Joint System® (MJS), a system consisting of a multi-articulated arm run by the patient on the three planes of space (**Figure 8**). The patient receives feedback from a computer system connected to the robot arm and adjusts his movements, following predefined trajectories. In this way, the patient learns to perform all the

**Figure 8.** Multi-Joint System®.

cases it is clear that intra-articular administration of corticosteroids improves and accelerate patients' healing. Long-term results about conventional therapies versus corticosteroids are comparable; due to understandable considering that adhesive capsulitis is a self-limiting

Another possible application of corticosteroids involves infiltration within the subacromial bursa; this method (**Figure 7**) is particularly useful in those cases of acute painful bursitis, in

Besides the corticosteroids, whose action and effectiveness are widely dealt in literature, the use of the viscosupplementation with hyaluronic acid is becoming increasingly widespread [111]. Hyaluronic acid acts through different mechanisms when injected into the joint. It is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial and neural tissues, is capable of retaining water and this contributes to cell adhesion, proliferation and migration. High local concentrations cause the release of growth factors, accelerating the tissue repair process [112]. The viscosupplementation is a way to restore rheological properties of the synovial fluid, enhancing viscoelastic properties of synovial fluid protecting

In the tendinitis involving the rotator cuff, viscosupplementation, not only protects the joint surface, but also restores the homeostasis of the chondrocytes [115]. The hypothesis that hyaluronic acid also acts on pain modulation has been investigated and Mitsui et al. [116] demonstrate that hyaluronic acid inhibits not only expression of mRNA for proinflammatory cytokines, such as IL-1b, IL-6 and TNF-a, but also COX-2/PGE2 (Prostaglandin E2) production via CD44 in IL-1-stimulated subacromial-synovium fibroblasts. CD44 is also present on synoviocytes, so it is a target for pain reduction. The restoration of the viscoelastic barrier around the nociceptive afferent fibers, reduces pain, hindering interaction with nociceptive

The rehabilitation program should always start from clinical evaluation, focusing on the status of functional deficiency, the range of motion and the pain elicited during evaluation [118]. The aim is to ensure long-term results in joint mobility, to reduce stiffness and improve function [119].

Maintaining the range of movements is essential to prevent adhesion and decrease impingement. To intervene on the strength of the rotator cuff muscles and on the scapula stabilizing muscles (anterior serratus, rhomboids, latissimus dorsi and trapezium) and the deltoid,

combination with other therapies aimed at treating the underlying cause.

cartilage from mechanical stress and reducing pain [113, 114].

pathology [110].

224 Advances in Shoulder Surgery

stimuli [117].

**5.3. Rehabilitation**

**Figure 7.** Sequence of subacromial bursa infiltration.

peculiar movements of the glenohumeral joint, maintaining a proper position of the scapula and increasing the strength of the anterior serratus, rhomboid, latissimus dorsi, trapezius and deltoid. MJS grant a better control of shoulder movements with increased proprioception, sensitivity and shoulder joint motion in a multi-dimensional axial-type range [123, 124].

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