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14 Articles in Volume 21, Issue #5
Analgesics of the Future: Interleukin-17 Inhibitors for Treating Psoriatic Arthritis
Ask the PharmD: What evidence exists for metformin in treating rheumatoid arthritis pain?
Case Chat: Spasms vs. Spasticity and Muscle Relaxant Options
CDC Opioid Prescribing Guideline Updates Are in the Works: Will the Changes be Enough?
Chronic Pain Management in Marginalized Populations: How to Rebalance the Provider-Patient Relationship
Dantrolene: The Forgotten Molecule for Outpatient Spasticity
Forgotten Analgesics: The Drugs Pain Practitioners Need to Reconsider
Machine Learning Predicts Patient Response to Rheumatoid Arthritis Therapy
Perspective: Where Have All the Rheumatologists Gone?
Rheumatoid Arthritis and Bridge Therapy: Primary Care Considerations
Root Cause of Plantar Fasciitis: Three-Step Exercise Protocol
Shoulder Pain and Rotator Cuff Injuries: Emerging Treatments
Special Report: The Evolution of Rheumatoid Arthritis Treatment, from Gold to Gene Therapy
Transfer of Care: Barriers and Solutions in Chronic Pain Management

Shoulder Pain and Rotator Cuff Injuries: Emerging Treatments

A mini literature review of conventional approaches – as well as novel treatments utilizing stem cell and platelet-rich plasma injections – for shoulder pain and related injuries.

The shoulder is one of the most complex joints in the human body. The humerus and scapula form the shoulder joint, supported by rotator cuff muscles and tendons.

The shoulder, especially the rotator cuff tendons, is highly susceptible to injury due to the extreme range of motion (ROM) that allows people to normally move their arms in almost every direction. Pain or reduction in ROM due to injury can limit a patient’s potential activity and cause impaired function and disability, often reducing the ability to perform simple daily tasks, such as hair brushing or getting dressed. Individuals who experience chronic pain and dysfunction in the shoulder may start to feel helpless, defeated, and/or depressed, leading to a reduced quality of life (QoL).


Shoulder Pain Causes

Per van der Wint et al, the reported annual incidence of shoulder pain in primary care is 14.7 per 1,000 patients per year1 with a lifetime prevalence of up to 70%.Shoulder pain can be difficult to diagnose and treat, often becoming chronic due to difficulties in implementing effective treatment. The prevalence of chronic shoulder pain can range from 15.5% to 41% rising from 23% in 18- to 24-year-olds, reaching a peak of 50% in 55- to 64-year-olds.3

Sources of shoulder pain are varied and can originate from many different anatomical sites, such as:4-6

  • most commonly, tendons (biceps tendinitis, rotator cuff tear, rotator cuff impingement, or rotator cuff tendinitis/tendinopathy)
  • joints (arthritis)
  • capsules (adhesive capsulitis)
  • bursae (subacromial bursitis)
  • suprascapular nerve (entrapment).

While widespread agreement exists that most cases of shoulder pain do not require surgery, there is no consensus on the effectiveness of stem cells or platelet rich plasma (PRP) as a treatment option. Here, we review the existing literature about the most common interventions and explore the modality of stem cell therapy with regard to rotator cuff  tendinosis and tendon tears, with the aim of providing guidance to clinicians when counseling patients on this type of therapy.

Rotator cuff injuries are often treated with acetaminophen or NSAIDs, steroid injections, and physical therapy, while tendinitis of the rotator cuff or the bicipital tendon is often treated with transcutaneous electrical nerve stimulation (TENS). (Image: iStock)

Rotator Cuff Injuries

Tendinitis and Tendinopathy Symptoms

Damage to the rotator cuff is typically caused by overuse or an abrupt strain on a tendon.  Common symptoms of tendinopathy and tears of the rotator cuff include stiffness, dyskinesis, pain, and weakness, usually experienced during external rotation and elevation. Patients tend to experience considerable discomfort when doing simple daily tasks.5

Ultrasound imaging of the affected rotator cuff tendons may reveal a hypoechoic thickening, indicating tendinosis,7 versus visualized splitting, which may indicate a rotator cuff tear.8

Rotator Cuff Treatments: Conventional Approaches

In addition to medication, such as acetaminophen and NSAIDs, steroid injections, and physical therapy, tendinitis of the rotator cuff or the bicipital tendon is often treated with transcutaneous electrical nerve stimulation (TENS) with variable success rates identified for each mode of treatment.9,10

Subacromial corticosteroid injections are a common treatment for patients with rotator cuff tendinopathy, although some controversy remains regarding long-term effectiveness.11,12 Several limitations (ie, side effects) to corticosteroid injection exist and should be considered (see Table I).

A variety of physical interventions are described in the literature to reduce shoulder pain, including positioning of the paretic arm, strapping and orthosis, robotic training, mirror therapy, and electrical stimulation; however, no specific intervention has been shown to be superior.14

Alternative treatment methods, therefore, should be considered, namely, regenerative therapies.


Shoulder Tendon Tears and Tendinopathies: Emerging Treatments

The following mini literature review is based on results from UpToDate and PubMed for the following search terms: rotator tendinopathy, rotator cuff, tendinopathy treatment, osteopathic manipulative treatment, acupuncture for rotator cuff, and rehabilitation principles. Approximately 81 articles and case reviews were assessed for clinical effect and significance of rotator cuff tendinopathy treatment options. To ensure the most current and updated research data, only articles published over the past 15 years were included. This narrowed the article selection down to 18 articles with the majority being RCTs, including both human and animal studies.

Based on this review, key findings from individual investigational treatments studied for rotator cuff injuries included:

  • Stem cell therapy − enhances healing process and prevents degeneration10,15
  • Prolotherapy − involves injecting dextrose and lidocaine into the tendon to encourage a repair response and improve long-term pain16
  • Sclerotherapy − involves injecting sclerosing substances to reduce neovascularity in the tendon17
  • Dry needling and injection of autologous blood or platelet rich plasma guided by ultrasound to stimulate healing18
  • Acupuncture − for short-term benefit and used as an adjunct treatment19
  • Shock wave therapy − for treating soft tissue injury and calcific tendinopathy20
  • Ultrasound therapy and laser therapy − to stimulate collagen production and overall improve tendon healing and strength21-23
  • Osteopathic manipulative medicine (Spencer technique) − shown to increase ROM24

The most commonly used treatments for rotator cuff injuries were:

  • Resistance exercises − to improve muscle strength, mobility, and function; to decrease pain and swelling25,26
  • Stretching − to relieve muscle spasm and lengthen muscles27
  • NSAIDs – for short-term pain relief and to reduce minor inflammation28-30 (see also topicals)
  • Glucocorticoid injections – for acute tendinopathy31,32
  • Nitroglycerin patches – to stimulate collagen in the tendon cells by utilizing nitric oxide13,33

Stem Cell and Platelet Rich Plasma for Rotator Cuff Pain

In recent years, significant research on the use of mesenchymal stem cells (MSCs) to enhance the healing process of rotator cuff dysfunctions has been done, usually in relatively small clinical trials or in vitro experimentation on tissue samples. MSCs have the ability to differentiate into various cell types including bone cells, muscles cells, fat cells, and tendon. Injection of these cells has been shown to have healing properties, increase strength, increase fibrocartilage formation and orientation, decrease lymphocyte infiltration, and decrease the immune response.10

(More on the evolution of MSCs in our PPM roundtable).

Interestingly, it has been found that the type of stem cell used – bone, tendon, or adipose – can lead to distinct outcomes for rotator cuff pain.

Bone marrow derived MSCs have been found to improve mechanical resistance. Further, when bone marrow aspirate concentrate is mixed with PRP, it has been demonstrated to enhance proliferation and migration of tendon-derived stem cells and prevent abnormal chondrogenic and osteogenic differentiation.34 When bone marrow was induced with scleraxis (transcription factor) or metalloproteinase inhibitor-1, it improved the biomechanical strength, resistance, stiffness, and fibrocartilage.33

From a post-operative standpoint, one study demonstrated the use of iliac crest bone marrow-derived MSCs on surgical rotator cuff repairs. The authors concluded that there was a significant improvement in the healing rate, recovery rate, and quality of the repaired surfaces compared to those who did not receive the bone marrow-derived injection. It later showed a decreased number of re-tears 10 years post MSC injection.35

In comparison, tendon-derived MSCs have been found to improve collagen and decrease inflammation.19

Adipose-derived MSCs were shown to improve muscle function, tendon healing, decreased atrophy, and improved muscle regeneration.10 It is worth noting that one study focused on the use of exosomes isolated from adipose-derived MSCs to prevent muscle degeneration. Study results indicated use of these exosomes prevented fatty infiltrations, inflammation, atrophy, and vascularization of muscles.15

With regard to PRP injections on the periarthritis shoulder, one study demonstrated that the use of just one PRP injection provided significant improvement of both active and passive ROM. PRP was also more effective at reducing pain and increasing shoulder function when compared to corticosteroid injections and ultrasonic therapy.13

Review Limitations

The limitations to this review included: the severity of shoulder pain among patients, the severity of the tendinopathy across patients, the type of activity that led to the tendinopathy, the level of function, the age of the patient, how often each patient rested versus activity level, and alternative diagnoses (such as arthritis gout, tendon xanthoma, systemic lupus erythematosus).

Also, four of the studies performed were on tendons other than the shoulder such as the Achilles, elbow, or patellar tendon. One of the studies utilized young rats rather than aged rats; rotator cuff tendinopathies are more common in elderly people. In addition, some of the studies were limited due to small sample size. Sufficient long-term follow-up was also a limitation.


New Treatments for Shoulder Pain: Practical Takeaways

Ultimately, most common treatment modalities used to manage rotator cuff injuries are medication management (eg, NSAIDs, steroid injections, and nitroglycerin patches) and physical therapy. Physicians may also consider implementing prolotherapy, dry needling, laser therapy, sclerotherapy, prolotherapy, and shock wave therapy. Acupuncture and osteopathic manipulation medicine have minimal side effects, so those approaches may be considered as an adjunct to treatment for all patients with significant shoulder pain as well.

More recently, MSCs have been shown to have significant healing properties as well as increasing shoulder range of motion, strength, and muscle function; and decreasing muscle degeneration, pain, and inflammation. Due to the reassuring results obtained from the clinical studies, further research is highly encouraged.

Last updated on: September 8, 2021
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