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Platelet rich plasma versus hyaluronic acid injection in chronic painful shoulder: Randomized blind clinical trial

1 Department of Rheumatology, Rehabilitation and Physical Medicine, Assiut University, Assiut, Egypt
2 Department of Rheumatology, Rehabilitation, and Physical Medicine, Ministry of Health Assiut, Egypt
3 Department of Clinical Pathology, Assiut University, Assiut, Egypt

Date of Submission15-Oct-2021
Date of Acceptance01-Apr-2022
Date of Web Publication06-Jul-2022

Correspondence Address:
Eman H EL-Hakeim,
Department of Rheumatology, Rehabilitation, and Physical Medicine Assiut University, Asyut
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_237_21


Background: Shoulder pain is considered a disabling problem and is a frequent reason for consultation in general practice. The prevalence of shoulder pain has been reported to range from 7% to 36% of population. Platelet-rich plasma (PRP) releases cytokines, which are delivered of the injury to facilitate healing. Hyaluronic acid (HA) has a lubricant and anti-inflammatory effect. The aim of this study was to compare the effect of PRP versus HA in the treatment of chronic shoulder pain.
Patients and Methods: This study was a prospective randomized trial on patients with chronic shoulder pain. Fifty patients were represented into two groups based on injected material: PRP group and HA group, assessment done before and after injections (4 weeks and 6 months) by using Visual Analog Scale (VAS), constant score (CS), and Shoulder Pain and Disability Index (SPADI).
Results: The study results showed that at 4 weeks after injection, the PRP group had a significantly higher Constant score in comparison to the HA group (60.91 ± 3.89 vs. 57.38 ± 6.22, P = 0.02), but no difference was at baseline and after 6 months. Furthermore, both groups had insignificant differences as regards baseline SPADI (58.77 ± 2.89 vs. 60.64 ± 3.51; P = 0.06) and 6-month follow-up after injection SPADI (55.44 ± 4.71 vs. 57.12 ± 4.40; P = 0.19), but at 4 weeks after injection, the PRP group had significantly lower SPADI in comparison to the HA group (53.52 ± 3.22 vs. 55.36 ± 2.98; P = 0.04).
Conclusion: Both PRP and HA groups showed statistically significant better outcomes in VAS, CS, and SPADI during follow-up visits, but PRP was found to be superior to HA at 4-week follow-up post injection.

Keywords: Chronic painful shoulder, hyaluronic acid, platelet-rich plasma, ultrasound

How to cite this URL:
EL-Hakeim EH, Selim ZI, Hamed Omran EA, Hosney M, Abd-Elkader AS. Platelet rich plasma versus hyaluronic acid injection in chronic painful shoulder: Randomized blind clinical trial. Indian J Rheumatol [Epub ahead of print] [cited 2022 Dec 5]. Available from:

  Introduction Top

Painful shoulder is considered a disabling problem and is a frequent reason for consultation in general practice. The prevalence of shoulder pain has been reported to range from 7% to 36% of population.[1],[2]

Chronic shoulder pain in the elderly may be underestimated and less properly treated.[3] Pain and stiffness of the shoulder joint are commonly caused by rotator cuff disorders including tendinitis and bursitis, adhesive capsulitis, and osteoarthrosis of the glenohumeral joint (GHJ).[4]

The use of blood derivatives and platelet-rich plasma (PRP) is trending for relieving joint pain and healing of the injured muscles and tendons, and also to improve the process of tissue repair via delivery of bioactive agents, which will provide chemotactic, proliferative, and anabolic cellular responses and enhance recovery of tissue function.[5] It is a large number of platelets in a small volume of plasma.[6],[7] PRP is derived from the centrifugation of the patient's own blood and it contains growth factors working on different target cells that improve wound healing, thereby playing an important role in tissue repair mechanisms, enhancing soft tissue healing and regeneration at various levels.[8] Due to the safety and availability of devices for outpatient preparations and delivery, the use of PRP has increased.[9] PRP development via centrifugation has greatly simplified, so it can be used in office settings as well as operating rooms.[7] These platelets enhance the release of a proportional quantity of cytokines, which are delivered of the injury to facilitate healing.[10] Researchers have shown the positive effect of PRP on different soft tissue damages such as chronic elbow tendinopathy, chronic Achilles tendinopathy, and rotator cuff tendon tears.[11]

Some studies had suggested that hyaluronic acid (HA) injection into the GHJ joint and the bursa is very well tolerated and may be effective in shoulder pain of various etiologies.[12] HA is thought to serve as a lubricant[13] and is reported to have an anti-inflammatory effect.[14] It has been suggested that exogenous HA induces endogenous HA synthesis, possibly stimulating the regenerative process within the joint.[15] Treatment of chronic shoulder pain usually includes oral analgesics, nonsteroidal anti-inflammatory drugs (NSAID), physical therapy, and/or corticosteroid injections aimed to improve pain, restore range of motion (ROM), and function of the shoulder and rotator cuff mechanism.[16],[17] Prolonged use of NSAID may be contra-indicated in elderly patients with comorbidities,[18],[19],[20] and also, local corticosteroid injection has been found, associated with hyperglycemia, harmful effects on articular cartilage, increased risk of tendon rupture, local skin depigmentation, and atrophy of subcutaneous tissue.[21] So many studies trying to find an effective and safest method for treatment chronic painful shoulder disordered, the use of PRP and HA injection have increased worldwide for injection in chronic degenerative arthritis. For these reasons, we were trying to find the effectiveness of both methods, which of them is superior in relieving pain, improving ROM, and activity of daily living of our patients.

The aim of this study was to compare the effect of ultrasound (US)-guided local injection of PRP versus HA for the treatment of chronic shoulder pain.

  Patients and Methods Top

This study was a prospective randomized double-blind clinical trial on patients with chronic shoulder pain presented at the outpatient clinic of Physical Medicine, Rheumatology, and Rehabilitation Department at Assiut university hospital from June 2019 to December 2020. Complete medical history, clinical examination, laboratory investigation, and imaging (X-ray or magnetic resonance imaging) were done for all patients to complete the diagnosis. Patients were represented into two groups: (PRP) group and (HA) group randomization done by sealed envelopes technique. Injections were performed under US guidance.

Inclusion criteria

  1. Adult patient age >18 years
  2. Patients with chronic shoulder pain more than 6 months not responding to medical treatment or physical therapy
  3. Frozen shoulder
  4. Rotator cuff (RC) (partial) tear.

Exclusion criteria

  1. Shoulder joint instability or traumatic shoulder pain
  2. Patients with local infection at the shoulder, systemic infection, or inflammatory disease (e.g., rheumatoid arthritis and hepatitis)
  3. Patients with a history of diabetes mellitus and malignancy (either hematological or nonhematological)
  4. Pregnancy
  5. Patients on anticoagulant therapy
  6. Injection of shoulder with corticosteroids in the preceding 6 months.

Preparation of platelet-rich plasma

Preparation of PRP: PRP was prepared and used at the time of treatment. For each patient, 20 ml blood was withdrawn under complete aseptic precautions. The process was carried out at room temperature (22c-25c) by using special vacuum tubes containing acid citrate dextrose (ACD) as an anticoagulant, labeled with identification data of patient. the blood was mixed gently through out the tubes. The tubes were subjected to the first centrifugation at 1500 rpm speed over 15 min, resulting in separation of the blood sample into a bottom layer of red blood cells, the middle layer consisting of platelet and buffy coat, and top layer of plasma. Then, the supernatant plasma and buffy-coat-containing platelet were transferred to another sterile tube (without anticoagulant) and eventually centrifuged at 3500 rpm over 7 min. Finally, the bottom one-fourth of the tube was obtained as PRP, where the platelets were settled down. Just before the injection of PRP, it was activated by the addition of 10% calcium chloride in a ratio of 1:10 with agitation through vigorous shaking.[22]

Injection technique

The procedure was done under complete aseptic conditions, PRP group were treated by single PRP injection, and HA group were treated by single HA injection, which was performed in the GHJ via the posterior approach or to subacromial space with needle (22 gauge) by US guidance using machine with linear array transducer frequency ranged from (10 to 19 MHz) high-frequency linear transducer MyLab 7 (Esaote, Europe B. V. Maastricht, Netherlands). The patients were instructed to avoid the use of NSAIDs 5 days before treatment. Both the participating patients and investigators were blinded to the treatment allocation.

Postinjection precautions

The plan of postinjection care:

  • Acetaminophen (paracetamol) was only allowed as analgesic after the procedure
  • Ice packs and rest for 72 h
  • Gradual return to activity).

Outcome measures

The outcome measures were assessed by using Visual Analog Scale of Pain (VAS) (0–10 score), Constant shoulder score (CS),[23] this score depends on a 100-point scale composed of a number of individual parameters. These parameters determined the level of pain and the ability to do normal daily activities of the patient. The Constant score was used to determine the functionality after the treatment of shoulder injury [Supplementary 1], and the Shoulder Pain and Disability Index (SPADI) questionnaire is a self-introduction administered index designed to measure the effects of different pathologic conditions on the functional status of the shoulder, which has two items: the first is the pain scale and the second item is the disability scale.[24] Assessment was done at baseline before injection, 4 weeks, and 6 months post injection [Supplementary 2].

Written and informed consent was obtained from all patients who participated in this study after they were informed about the nature of the procedure, any adverse reaction that may occur, and the benefits of injection. The study was approved by the Ethical Medical Committee of faculty of medicine of Assiut university according to the guidelines of the Helsinki Declaration and was registered at Clinical (NCT05072899).

Statistical analysis

Data were collected and analyzed for those using SPS (Statistical Package for the Social Science, version 20, IBM, and Armonk, New York, USA). Continuous data were expressed in the form of mean ± standard deviation or median (range), while nominal data were expressed in the form of frequency (percentage). Chi-squared test was used to compare the nominal data of both studied groups, while continuous data of both groups were compared with the Student's t-test. VAS, Constant score, and SPADI of each group were compared at baseline with different times of follow-up by the Paired t-test. The level of confidence was kept at 95%, and hence, P value was considered significant if < 0.05.

  Results Top

The study was started by doing assessment for 85 patients with chronic shoulder pain. Fifteen patients were excluded or declined to participate, 40 patients were injected by PRP, 30 patients injected by HA, and 15 patients missed during follow-up period. More details are shown flowchart [Figure 1]. The studied patients were two groups: PRP group (25 patients) and HA group (25 patients) according to the type of injection. The mean age of the PRP group was 46.52 ± 5.21 years and majority (76%) of patients were females, while the mean age of the HA group was 47.44 ± 5.14 years, majority were females (68%).
Figure 1: Flowchart of study participants

Click here to view

The most frequent affected shoulder was the right side in both groups (68% of the PRP group and 60% of the HA group). The mean duration was 7.92 ± 0.95 months in the PRP group and 7.88 ± 0.83 months in the HA group. It was noticed that 22 (88%), 2 (8%), and 1 (4%) patient of the PRP group and 19 (76%), 3 (12%), and 3 (12%) patients of the HA group had adhesive capsulitis, rotator cuff disorders, and osteoarthritis of the GHJ, respectively. Both groups had insignificant Constant score (CS) and SPADI which are summarized in [Table 1].
Table 1: Baseline data of studied groups

Click here to view

Visual Analog Scale among both studied groups

The study results showed that both groups had insignificant differences as regards baseline VAS (6.44 ± 0.96 vs. 6.68 ± 0.98; P = 0.38) and 6-month follow-up after injection VAS (5.84 ± 1.14 vs. 6.28 ± 1.27; P = 0.20), but at 4 weeks after injection, PRP group had significantly lower VAS in comparison to HA group (3.40 ± 0.76 vs. 4.08 ± 1.15; P = 0.01). In both groups, VAS had a downward trend at 1st month after injection, but at 6th month after injection, VAS showed an upward trend in comparison to 4 weeks VAS but still significantly lower in comparison to the baseline VAS, as shown in [Table 2].
Table 2: Visual Analog Scale, Constant score, and Shoulder Pain and Disability Index in both studied groups

Click here to view

Constant score (CS) among both studied groups

In the results, we noticed that both groups had insignificant differences as regards baseline Constant score (48.72 ± 5.63 vs. 47 ± 3.91, P = 0.23) and 6-month follow-up after injection Constant score (52.84 ± 5.67 vs. 50.78 ± 6.94, P = 0.25), but at 4 weeks after injection, PRP group had significantly higher Constant score in comparison to HA group (60.91 ± 3.89 vs. 57.38 ± 6.22, P = 0.02). In both groups, Constant score had an upward trend at 4 weeks after injection, but at 6th month after injection, Constant score showed a downward trend in comparison to 4 weeks Constant score but still significantly higher in comparison to the baseline Constant score, as shown in [Table 2] and [Figure 2].
Figure 2: Constant score in both studied groups PRP: Platelet-rich plasma; HA: Hyaluronic acid

Click here to view

The Shoulder Pain and Disability Index among both studied groups

It was noticed that both groups had insignificant differences regarding baseline SPADI (58.77 ± 2.89 vs. 60.64 ± 3.51; P = 0.06) and 6-month follow-up after injection SPADI (55.44 ± 4.71 vs. 57.12 ± 4.40; P = 0.19), but at 4 weeks after injection, PRP group had significantly lower SPADI in comparison to HA group (53.52 ± 3.22 vs. 55.36 ± 2.98; P = 0.04). In both groups, SPADI had a downward trend at 4 weeks after injection, but at 6 months after injection, SPADI showed an upward trend in comparison to 4 weeks SPADI but still significantly lower in comparison to the baseline SPADI, as shown in [Table 2] and [Figure 3].
Figure 3: Shoulder Pain and Disability Index in both studied groups PRP: Platelet-rich plasma. HA: Hyaluronic acid

Click here to view

  Discussion Top

Shoulder disorders are recognized as a disabling problem that affects daily functioning and working ability of the individuals. This is a common cause of chronic pain leading to loss of productivity and high social costs.[16]

The use of PRP for the treatment of painful shoulder conditions has increased worldwide. PRP is a part of the whole blood containing concentrated growth factors and proteins.[11] Furthermore, several studies have confirmed that HA interacts with mediators of inflammation, reduces apoptosis in osteoarthritic cartilage, stimulates chondrocyte growth and the synthesis of extracellular matrix proteins, and inhibits nociceptive receptors of pain.[25]

In this study, we used VAS, CS, and SPDI questionnaire for assessment and follow-up of the patients. The results show significant improvement in VAS Scale on weeks 4 and 6-month follow-up post injection for both PRP and HA. It was noticed that the PRP group has a significant improvement in VAS in comparison to the HA group (P = 0.01) only on weeks 4.

This is in agreement with a study done by Cai et al., they did a comparative study between sodium hyaluronate (SH), PRP, SH + PRP, and normal saline injection. They found that the VAS score showed a downward trend at 1 and 3 months in three groups (PRP, SH, and SH + PRP), but no reduction in pain was noticed after 3 months.[26]

The study results were in agreement with Calis et al., they did their study on patients with shoulder pain for at least 3 months with 50% limited ROM in at least one direction and VAS score >5. Under sonography guidance, PRP injection was performed to the GHJ. Significant improvements were detected in VAS scores on weeks 2, 6, and 12 when compared with baseline (P < 0.05),[27] also our results were in accordance with the results of a comparative study between PRP and hydrodissection with steroids. They noticed a significant improvement in both groups in 2-months follow-up post injection.[28]

In addition, another study comparing PRP and hydrodissection for adhesive capsulitis showed that PRP therapy is superior with P < 0.001 for VAS score.[29]

Our results in agreement with Cai et al., they found that in the SH group, the Constant score gradually improved, while in the PRP and the SH + PRP groups, the Constant score had a similar upward trend after the final injection. The Constant score was higher in the PRP and SH + PRP groups compared with the SH and normal saline groups at 6 months, and there was a similar consistent trend after 6 months.[26]

We noticed that the PRP and the HA groups had a significantly lower SPADI on 4-week and 6-month follow-up, these were in agreement with Calis et al., they noticed that both PRP and HA groups had significantly lower SPADI (P ≤ 0.001) in comparison to baseline. Furthermore, PRP group had a significant improvement in SPADI in comparison to HA group (P = 0.04). SPADI questionnaire in all time points when compared with baseline (P < 0.05),[27] in accordance with Ibrahim et al., they found that patients had severe functional limitation and disability as assessed by the Shoulder Disability Questionnaire and remarkably improved in both PRP and corticosteroid groups post injection.[28] In addition, the study of Zafarani et al. showed that PRP injection had a positive effect on improved pain, function, and shoulder joint ROM in partial thickness rotator cuff tears. Patients report 53% improvement in shoulder ROM, 66% in pain, 76% in shoulder hand disability score, and 84% in SF-12 Health Survey questionnaire.[30]

The study of Barman et al. involved patients diagnosed with adhesive capsulitis of the shoulder. In intra-articular corticosteroid (IA-CS) group, 30 patients received a single injection of IA-CS, and in PRP (IA-PRP) group, 30 patients received a single IA-PRP injection into the GHJ under US guidance. They conclude that at 12-week follow-up, a single dose of IA-PRP injection was found to be more effective than an IA-CS injection, in terms of improving pain, disability, and shoulder range of movement in patients with adhesive capsulitis of the shoulder.[31]

A possible explanation for pain relief in the PRP group was related to platelet antinociceptive properties. This antinociceptive effect of PRP may be due to the augmentation of cannabinoid (CB) receptors, CB1 and CB2.[32] In addition, a retrospective cohort comparison conducted by Jiménez-Martin et al. showed that PRP had a role in improving the pain score and reducing rehabilitation time in patients who underwent arthroscopic subacromial surgery.[33] Autologous PRP therapy improves the functional quality of life with a long-term outcome. In adhesive capsulitis of shoulder, autologous PRP therapy remains functionally superior to hydrodissection as autologous PRP is a constructive procedure by regenerating the degenerative tissues.[29]

On the other hand, Kesikburun et al. compared injecting PRP and saline for the treatment of rotator cuff tendinopathy or partial tendon ruptures and found no difference after a 1-year follow-up.[34] Furthermore, both Castricini et al.[35] and Jo et al.[36] reported no differences in pain scores and functional scores between the PRP and the control groups in patients undergoing rotator cuff surgery.

In the current study, the HA group showed statistically significant improvement regarding VAS, CS, and SPADI. These results were in agreement with Blaine et al. who evaluated the effect of intra-articular injections of SH in the relieving of shoulder pain and on the movement in patients with persistent shoulder pain resulting from GHJ osteoarthritis, RC tears and/or adhesive capsulitis; patients who were treated with SH had a greater pain relief than controls.[37] Honda et al. in their study suggested that the relevance of the clinical application of HA accelerates tendon-to-bone healing after rotator cuff repair.[38] Furthermore, significant recovery of pain was observed in the group to which SH was implemented to adhesive capsulitis in the 15th day and in the 3rd month when compared to the control group.[39] Two studies[40],[41] evaluated the use of HA compared to physical therapies, concluding that HA injection is safe and effective for patients with rotator cuff pathology. Furthermore, Shibata et al.[42] and Chou et al.[43] found that SH was effective and well tolerated for the treatment of rotator cuff injury with or without complete tears. Frizziero et al.[44] demonstrated that in patients with rotator cuff tendinopathy, intra-articular injections of HA provided prompt clinical improvement compared with extracorporeal shockwave therapy.

The PRP injection and the HA injection are found to be effective in improving quality of life, pain, and disability in patients with chronic shoulder pain. In this study, injections were performed once. It is uncertain whether more than one injection would be more beneficial. An additional injection may be beneficial for the patients who did not show favorable outcomes or only partial therapeutic effects.

The limitations of this study were small sample size and lack of a control group for comparison. It is therefore difficult to know the extent to which these subjects would have improved without PRP or HA injection. We could not include a control group because it is unethically to do invasive technique with placebo in patients with chronic pain, also the unknown optimal concentration and dosage of PRP, the unknown optimal administration times for both PRP and HA, and the time points at which data are collected.

  Conclusion Top

We concluded that injection of PRP and HA in chronic shoulder pain is safe, reliable, effective, and with good clinical outcomes. The PRP was found to be superior to HA after 1 month of follow-up, then they appeared to be equally effective after 6 months of injection.


Advancement of research and future long-term studies need to be performed to corroborate the findings of this study before this treatment becomes widely accepted. Furthermore, more cases and larger multicenter studies are warranted to verify the effects of PRP and HA injections.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]


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