The use of platelet-rich plasma in management of musculoskeletal pain: a narrative review

Article information

J Yeungnam Med Sci. 2022;39(3):206-215
Publication date (electronic) : 2022 June 8
doi :
Department of Physical Medicine and Rehabilitation, University of Medicine, Mandalay, Myanmar
Corresponding author: Aung Chan Thu, MD, PhD Department of Physical Medicine and Rehabilitation, University of Medicine, 30th Street, Between 73rd & 74th Streets, Mandalay, Myanmar Tel: +95-9977277511 • E-mail:
Received 2022 April 26; Revised 2022 May 13; Accepted 2022 May 17.


Musculoskeletal pain is the most common pain reported by patients. Platelet-rich plasma (PRP) is widely used to treat musculoskeletal pain. However, the efficacy of PRP to treat this pain remains controversial. This review highlights the application of PRP in the treatment of musculoskeletal pain. PRP treatment appears to reduce pain and improve function in patients with musculoskeletal pain. However, there are limitations to the currently published studies. These limitations include the PRP preparation methods, type of activators, types of pathology to be treated, methods and times of administration, and association of PRP with other treatments.


Among clinically associated pain conditions, musculoskeletal (MSK) pain is the most frequent [1]. MSK diseases are the most common cause of severe long-term pain and physical disability and have a major impact on the quality of life of patients [2,3]. MSK pain affects hundreds of millions of people around the world [4].

The primary goal of physiatrists is to optimize the pain management of their patients with various MSK conditions, including acute and chronic muscle, tendon, ligament, and cartilage disorders. The traditional management of MSK pain involves control with conservative “Rest, Ice, Compression, Elevation” treatment and physical therapy to corticosteroid injections coupled with specific rehabilitation exercises [5].

Although the traditional management of MSK pain may be helpful for short-term pain reduction and early recovery of function, it does not typically reverse the structural changes associated with degenerative conditions. Recently, the multidisciplinary field of tissue engineering has been expanding to enhance healing and stimulate growth in injuries of soft tissue and bone [6].

Platelet-rich plasma (PRP) is one research area that has developed rapidly in recent years. Historically, hematologists coined the term PRP in the 1970s, and platelets have been used to treat patients with hemorrhage or thrombocytopenia [6,7]. The clinical use of PRP as a cell and tissue engineering therapy has dramatically increased over the last decade [8].

PRP is a biological product defined as the plasma fraction of autologous blood with a platelet concentration above baseline after centrifugation [9]. PRP contains many biologically active factors such as platelet-derived growth factor, transforming growth factor-beta (TGF-β), insulin-like growth factor, vascular endothelial growth factor, and epidermal growth factor [10]. PRP concentrates can promote the supraphysiological release of growth factors to enhance healing in chronic injuries, accelerate the acute injury repair process, and reduce MSK pain [11].

Platelet-rich plasma

PRP is defined as the plasma fraction of autologous blood with a platelet concentration above baseline after centrifugation [9]. Platelets are irregularly shaped, non-nucleated cytoplasmic bodies derived from fragmentation of megakaryocyte precursors. Platelets are important in blood clot formation, thrombosis and hemostasis, immunity, inflammation, wound healing, hematological malignancies, and metabolic disorders [12].

PRP contains growth factors that promote cellular anabolism and enhance the release of inflammatory mediators and modulators that exert anti-inflammatory and analgesic effects [13]. PRP counteracts the inflammatory cascade [14]. PRP treatment has been shown to induce the release of hepatocyte growth factor (HGF), a major anti-inflammatory factor. Growth factors (HGF, interleukin-4, and tumor necrosis factor-alpha [TNF-α]) reduce the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2, which are proinflammatory mediators. Additionally, PRP can suppress the production of nuclear factor kappa-light-chain-enhancer of activated B cells, which is highly relevant in soft tissue inflammation [15,16].

PRP promotes tissue regeneration and has gained popularity in recent decades [16]. PRP can induce the production of collagen and growth factors and might increase stem cell numbers, which consequently promotes the healing process by delivering high concentrations of alpha-granules containing biologically active moieties (such as vascular endothelial growth factor and TGF-β) to areas of soft tissue damage [17]. PRP also stimulates cell proliferation and cartilaginous matrix production by chondrocytes and adult mesenchymal stem cells (MSCs). Findings from current clinical trials suggest that PRP has the potential to enhance cartilage repair, attenuate arthritis symptoms, and improve joint function with an acceptable safety profile [13].

Composition of platelet-rich plasma

PRP is the plasma from autologous blood after centrifugation and contains a rich concentration of platelets and a variety of growth factors, cytokines, chemokines, and proteins [18]. The key growth factors in PRP are summarized in Table 1. The composition of growth factors promotes tissue repair and regeneration, enhances angiogenesis, and plays a vital role in anti-inflammatory and analgesic effects [19].

Growth factors contained in platelet-rich plasma and their major physiological actions

Knee osteoarthritis

Symptomatic knee osteoarthritis (OA) is a leading cause of disability globally with a significant financial impact [20]. The development of knee OA involves not only the cartilage but also the entire joint, with changes in the articular bone, synovial membrane, joint capsule, ligaments, and musculature around the joint [21].

There is no disease-modifying therapy for the management of OA; therefore, the treatment goals are to improve pain and function. Pharmacotherapy management includes topical and oral nonsteroidal anti-inflammatory drugs, duloxetine, and periodic intra-articular glucocorticoid and hyaluronan injections [22].

PRP containing growth factors stimulates local angiogenesis, regulates inflammation, inhibits catabolic enzymes and cytokines, and recruits local stem cells and fibroblasts to the damaged sites. PRP also induces nearby healthy cells to synthesize greater amounts of growth factors and increase endogenous hyaluronan synthesis with few serious side effects [23-26]. In recent years, PRP has emerged as a viable treatment method for the management of knee OA [27]. Eighteen studies (all level 1) involving 811 patients undergoing intra-articular PRP injection (mean age, 57.6 years) and 797 patients undergoing hyaluronic acid injection (mean age, 59.3 years) showed that the mean improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores was significantly higher in the PRP group (44.7%) than in the hyaluronic acid group (12.6%) (p<0.01) [28].

Many systematic reviews and meta-analyses have found positive results for PRP in relieving pain and improving function in knee OA [27-30]. Therefore, PRP can be expected to improve pain and function in the management of knee OA, although further studies are needed for the definitive assessment of knee OA treatment.

Ankle joint osteoarthritis

Ankle OA is rarer than OA of the hip and knee and is more common in young active individuals, with a prevalence of 3.4% in the general adult population [31,32]. The primary etiology of ankle OA is trauma, and the overall risk of developing posttraumatic ankle OA after 20 years is almost 40%. The management of ankle OA involves nonsurgical options (medications, physical therapy, orthotics and insoles, and intra-articular injections) and surgical options (joint-sparing surgery, total ankle arthroplasty, and ankle arthrodesis) [33].

Individuals with ankle OA, hemophilic arthropathy, and rheumatoid arthritis were included in 27 studies (1,085 patients). Most of these studies were observational. A case series found that PRP, MSC, hyaluronic acid, and corticosteroid injections provided symptomatic relief, although the efficacy of corticosteroid injections was short-term [34].

PRP injections for ankle OA are valid and safe alternatives for postponing the need for surgery [31]. PRP injections are favored for the treatment of pain associated with ankle OA. However, the relative efficacy of PRP injection therapy is far from definitive and warrants further high-quality comparative trials [34].

Temporomandibular joint osteoarthritis

The prevalence of temporomandibular (TM) joint OA is increasing, and it is more common in women. OA may cause pain in the TM joint area [35,36]. Excessive or prolonged overload of TM joints may lead to adverse remodeling, resulting in OA. The management of TM OA includes conservative treatment (medications, splints, and physiotherapy), intra-articular injections, arthrocentesis, arthroscopy, and open-joint surgery [37].

A comparative randomized study showed that maximum improvements in pain-free mouth opening and reduction in pain severity were observed in all groups (bite splint, betamethasone, sodium hyaluronate, and PRP injections in addition to using the bite splint). In the PRP group, patients with a maximum pain-free mouth opening value of 25.8 mm before treatment improved to 46.8 mm after treatment. The PRP group showed the best results after 6 months [38].

PRP injections may reduce pain and joint sound and improve the range of motion of the TM joint because PRP injections have anti-inflammatory and analgesic properties. PRP restores intra-articular hyaluronic acid levels, increases chondrocyte glycosaminoglycan synthesis, and balances joint angiogenesis. However, a standardized protocol for PRP preparation and application needs to be established [37-40].

Low back pain

Low back pain (LBP) involves a spectrum of different types of pain (e.g., nociceptive, neuropathic, nociplastic, and nonspecific) that frequently overlap. LBP can be caused by lumbar spine elements (e.g., soft tissue, vertebrae, zygapophyseal and sacroiliac joints, intervertebral discs, and neurovascular structures) [41]. Therapy for LBP usually begins with self-care and medication in combination with non-pharmacological methods, such as physical therapy and psychological treatment, in appropriate patients [42].

Systematic reviews and single-arm meta-analyses showed that PRP may be effective in managing discogenic LBP, radicular pain, facet joint pain, and sacroiliac joint pain. However, the levels of evidence vary [43,44]. Intradiscal PRP injections can be a safe, inexpensive, and feasible treatment to counter the intervertebral disc degeneration associated with LBP. It is important to administer PRP early during the course of treatment to stimulate growth of the remaining cells in the disc [45,46]. PRP injections in the lumbar multifidus muscle can be a safe and inexpensive approach to treating LBP [47]. A small number of prospective trials have described that PRP injection may improve the pain or functional decline caused by facet joint arthropathy for a longer duration [48].

In 2017, a prospective comparative study including 46 patients showed statistically significant pain reduction in both groups (PRP, group A and corticosteroid/local anesthesia, group B). However, for subjective satisfaction based on the modified MacNab criteria, the success rate for group B remained at 20% after 6 months, while it increased over time in group A. Therefore, autologous PRP was suggested as a superior treatment option for long-duration efficacy in lumbar facet joint syndrome [49].

Twenty patients completed another prospective clinical trial. The improvements in pain scores (numerical rating scale and Oswestry Disability Index scores) were positively correlated with platelet concentrations in the PRP group [46].

In conclusion, the use of PRP in various injections, such as intradiscal, intrafacet, and intramuscular injections, has yielded significantly reduced pain and improved patient satisfaction, with a significant advantage of no major complications. However, further studies with larger sample sizes and control groups are needed to confirm its efficacy [43,44,48,50].

Myofascial pain syndrome

Myofascial pain is an important cause of disability in the whole population [51]. Emerging symptoms arise from each painful myofascial trigger point, which is a hypersensitive spot within a taut band of skeletal muscle that produces pain on compression, stretch, overload, or contraction of the tissue. The end result is usually pain that is perceived to be distant from the spot of origin. In a randomized controlled trial, there was no statistically significant difference in pain levels between the “lidocaine” and “PRP” groups before and 2 weeks after treatment; however, a statistically significant difference was found between the two groups 4 weeks after treatment (p<0.001). Specifically, 4 weeks after the injection, the average pain of the patients in the lidocaine and PRP groups was 3.4 and 0.9 on the visual analogue scale (VAS), respectively [52].

There are a few studies associated with myofascial pain that were conducted only on the masticatory muscles, which are involved in the most common TM disorders. PRP injections effectively improved trigger-point symptoms in the masseter muscle at 1 and 3 months [52,53].

Lateral epicondylitis

As tendons have poor vascularity, the tissue has limited healing and the lesions are not reversible, resulting in tendinopathies due to trauma or excessive overload. This causes tendon soreness, reduced strength, pain upon exertion, and progressive reduction in function [54].

Lateral epicondylitis, also known as tennis elbow, is a common musculotendinous degenerative disorder of the extensor origin at the lateral humeral epicondyle in adults [55], with a prevalence of 1% to 3% in the general population [56]. The presenting symptoms include lateral elbow pain, pain caused by wrist extension, and weakened grip strength. The diagnosis is always made clinically through medical history and physical examinations [57]. The treatment of lateral epicondylitis includes rest, nonsteroidal anti-inflammatory medication, bracing, physical therapy, extracorporeal shock wave therapy (ESWT), and botulinum toxin injection [58].

Compared with lateral epicondyle surgery, PRP injections provide similar improvements in pain and function in patients suffering from lateral epicondylitis [59]. PRP components promote cell recruitment, proliferation, and angiogenesis. It has also been suggested that PRP induces a transient inflammatory response, resulting in a regenerative response and immunomodulatory effects on tenocytes [60].

A randomized study involving 83 patients was conducted in 2007. The study was composed of two groups: group A, local steroid injection (n=50) and group B, autologous PRP (n=33). A significant difference between the two groups (p=0.0001) was found in pain and function at the end of 6 months. Group B showed a 91% mean improvement (8.33–0.69) in VAS score compared to a 42.2% mean improvement (7.98–4.61) in group A. Regarding function assessment, MAYO Elbow Scores also indicated a favorable outcome in the PRP-treated patients (group B) with a 54.4% mean improvement (61.51–95.0) compared to a 1.25% mean improvement (63.92–63.12) in the steroid-treated patients (group A), a difference that was statistically significant (p=0.0001) [61].

Many systematic reviews and meta-analyses have found that PRP can be considered a safe and effective treatment option for lateral epicondylitis with clinical improvements in pain and function, although there is a lack of quantification of specific PRP content and considerable heterogeneity among randomized controlled trials exists [62-65].

Plantar fasciitis

Plantar fasciitis is a common cause of heel pain and is associated with significant morbidity. It is a debilitating degenerative condition of the plantar fascia resulting from repetitive microtrauma and excessive strain on the plantar surface of the foot [66]. PRP may modulate plantar fascia degeneration because of its regenerative properties [67]. PRP also releases vascular endothelial growth factor, which increases angiogenesis and may facilitate the healing of degenerative conditions by promoting neovascularization and repair [68].

PRP has been suggested as a safe therapeutic option in the treatment of plantar fasciitis, as it reduces pain and improves function in patients with this condition, and its effect persists long term [69-71].

Patellar tendinopathy (jumper’s knee)

Patellar tendinopathy (PT) is referred to as “jumper’s knee,” a clinical and chronic overuse condition of unknown pathogenesis and etiology [72]. A large proportion of patients are refractory to conservative treatment, and a variety of new treatments have emerged, including PRP injections [73]. PRP-containing growth factors have been shown to play a role in tendon healing [74,75]. The growth factors in PRP have been observed to play crucial roles in the tissue healing process, collagen production, and tendon cell proliferation [76].

To compare PRP with focused ESWT among athletes with chronic PT, a randomized controlled single-center trial with 12 months of follow-up was performed. During the 12-month follow-up period, the Victorian Institute of Sport Assessment-Patella questionnaire scores for both groups improved significantly from baseline (55.3 for PRP, 56.1 for ESWT), although the PRP group showed greater improvement at 6 months (86.7 vs. 73.7, p=0.014) and 12 months (91.3 vs. 77.6, p=0.026). The pain scores during five single-leg squats demonstrated similar trends. At 12 months, a greater proportion of patients in the PRP group rated their response to treatment as good or excellent (PRP, 91.3% vs. ESWT, 60.8%; p=0.035) [77].

Therefore, PRP plays a potential role in the treatment of PT, leading to a significant decrease in pain and significant improvement in knee function and quality of life over 12 months [78-82].

Rotator cuff tendinopathy

More than 50% of all shoulder pain cases are considered to be related to tendinopathies of the rotator cuff (RC), such as tendinosis and incomplete thickness tears of the supraspinatus [81]. In the management of RC tendinopathy, physical rehabilitation, rest, and nonsteroidal anti-inflammatory drugs are considered conventional treatments; however, the best treatment is still inconclusive [83,84].

PRP has been reported to promote the proliferation of two tendon cell types; tenocytes and tendon stem/progenitor cells. Several studies have shown that PRP can induce tenocyte proliferation in vitro [85].

For patients with RC tendinopathy, corticosteroids yield pain reduction and functional improvement in the short term (3–6 weeks), but not in the long term (over 24 weeks). In contrast, PRP may yield better long-term outcomes (more than 24 weeks) [86].

Moreover, the long-term retear rates of RC-related abnormalities were significantly decreased in patients who received PRP [87].

Many systematic reviews and meta-analyses have found that the currently available clinical evidence on PRP injections supports a beneficial effect on pain reduction and functional outcomes in RC tendinopathy [88-91].

Adhesive capsulitis

Adhesive capsulitis (AC) of the shoulder is a common clinical condition characterized by insidious and progressive pain resulting in loss of glenohumeral joint function [92]. However, the etiology of AC remains unclear. It has been postulated that the motion limitations of the shoulder joint are due to an imbalance between fibrosis and loss of normal collagenous remodeling after an inflammatory healing response [93].

PRP can exert an anti-inflammatory effect at the inflammation site by releasing TNF-α, HGF, and lipoxin A4, which are potent anti-inflammatory agents [94,95].

At the 12-week follow-up in another study, a single injection of PRP was found to be more effective than corticosteroid injection in improving pain, disability, and shoulder range of movement in patients with AC [96].

PRP injections have been found to be effective in reducing pain and improving shoulder joint function due to AC [93,96,97]. These findings suggest that PRP is a therapeutic option for the management of AC.

Adverse effects

The most common adverse effect was mild pain and discomfort at the injection site after PRP injection [98]. Some authors have reported that PRP injections are more painful than saline injections. However, no serious adverse effects were observed [99].


Although good clinical outcomes and safety profiles can be achieved with the use of PRP, there are discrepancies in the existing literature. Several variables must be considered when using PRP. However, these variables were not described herein. PRP preparation methods, types of activators, types of pathology to be treated, routes and times of administration, and the association of PRP with other treatments can influence outcomes. Although several research articles have been published on PRP, this field still requires more scrutiny because of the inconsistent results of different studies, and a definite direction remains elusive.


This review article presents available evidence supporting the clinical efficacy of PRP in patients with MSK pain, with fewer side effects. PRP leads to reductions in pain and improvements in patient's function; however, evidence to clarify the discrepancies in PRP therapy is still needed.


Conflicts of interest

No potential conflict of interest relevant to this article was reported.




1. Casser HR, Schaible HG. Musculoskeletal pain. Schmerz 2015;29:486–8. :490–5.
2. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003;81:646–56.
3. Marks R. Qigong and musculoskeletal pain. Curr Rheumatol Rep 2019;21:59.
4. Hawker GA. The assessment of musculoskeletal pain. Clin Exp Rheumatol 2017;35(5 Suppl 107):8–12.
5. Sepúlveda F, Baerga L, Micheo W. The role of physiatry in regenerative medicine: the past, the present, and future challenges. PM R 2015;7(4 Suppl):S76–80.
6. Middleton KK, Barro V, Muller B, Terada S, Fu FH. Evaluation of the effects of platelet-rich plasma (PRP) therapy involved in the healing of sports-related soft tissue injuries. Iowa Orthop J 2012;32:150–63.
7. Alves R, Grimalt R. A review of platelet-rich plasma: history, biology, mechanism of action, and classification. Skin Appendage Disord 2018;4:18–24.
8. Bos-Mikich A, de Oliveira R, Frantz N. Platelet-rich plasma therapy and reproductive medicine. J Assist Reprod Genet 2018;35:753–6.
9. Alves R, Grimalt R. Randomized placebo-controlled, double-blind, half-head study to assess the efficacy of platelet-rich plasma on the treatment of androgenetic alopecia. Dermatol Surg 2016;42:491–7.
10. Cao Y, Zhu X, Zhou R, He Y, Wu Z, Chen Y. A narrative review of the research progress and clinical application of platelet-rich plasma. Ann Palliat Med 2021;10:4823–9.
11. Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-rich plasma: new performance understandings and therapeutic considerations in 2020. Int J Mol Sci 2020;21:7794.
12. Linden MD. Platelet physiology. Methods Mol Biol 2013;992:13–30.
13. Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther 2014;16:204.
14. Wu CC, Chen WH, Zao B, Lai PL, Lin TC, Lo HY, et al. Regenerative potentials of platelet-rich plasma enhanced by collagen in retrieving pro-inflammatory cytokine-inhibited chondrogenesis. Biomaterials 2011;32:5847–54.
15. Bendinelli P, Matteucci E, Dogliotti G, Corsi MM, Banfi G, Maroni P, et al. Molecular basis of anti-inflammatory action of platelet-rich plasma on human chondrocytes: mechanisms of NF-κB inhibition via HGF. J Cell Physiol 2010;225:757–66.
16. Solakoglu Ö, Heydecke G, Amiri N, Anitua E. The use of plasma rich in growth factors (PRGF) in guided tissue regeneration and guided bone regeneration: a review of histological, immunohistochemical, histomorphometrical, radiological and clinical results in humans. Ann Anat 2020;231:151528.
17. Gautam VK, Verma S, Batra S, Bhatnagar N, Arora S. Platelet-rich plasma versus corticosteroid injection for recalcitrant lateral epicondylitis: clinical and ultrasonographic evaluation. J Orthop Surg (Hong Kong) 2015;23:1–5.
18. Kaushik A, Kumaran MS. Platelet-rich plasma: the journey so far! Indian Dermatol Online J 2020;11:685–92.
19. Dhillon RS, Schwarz EM, Maloney MD. Platelet-rich plasma therapy: future or trend? Arthritis Res Ther 2012;14:219.
20. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73:1323–30.
21. Bliddal H. Definition, pathology and pathogenesis of osteoarthritis. Ugeskr Laeger 2020;182:V06200477.
22. Block JA, Cherny D. Management of knee osteoarthritis: what internists need to know. Med Clin North Am 2021;105:367–85.
23. Cugat R, Cuscó X, Seijas R, Álvarez P, Steinbacher G, Ares O, et al. Biologic enhancement of cartilage repair: the role of platelet-rich plasma and other commercially available growth factors. Arthroscopy 2015;31:777–83.
24. Anitua E, Sánchez M, Nurden AT, Zalduendo MM, de la Fuente M, Azofra J, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology (Oxford) 2007;46:1769–72.
25. Sun SF, Lin GC, Hsu CW, Lin HS, Liou IS, Wu SY. Comparing efficacy of intraarticular single crosslinked Hyaluronan (HYAJOINT Plus) and platelet-rich plasma (PRP) versus PRP alone for treating knee osteoarthritis. Sci Rep 2021;11:140.
26. Cook CS, Smith PA. Clinical update: why PRP should be your first choice for injection therapy in treating osteoarthritis of the knee. Curr Rev Musculoskelet Med 2018;11:583–92.
27. Shen L, Yuan T, Chen S, Xie X, Zhang C. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res 2017;12:16.
28. Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Am J Sports Med 2021;49:249–60.
29. Zhao J, Huang H, Liang G, Zeng LF, Yang W, Liu J. Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord 2020;21:224.
30. McLarnon M, Heron N. Intra-articular platelet-rich plasma injections versus intra-articular corticosteroid injections for symptomatic management of knee osteoarthritis: systematic review and meta-analysis. BMC Musculoskelet Disord 2021;22:550.
31. Repetto I, Biti B, Cerruti P, Trentini R, Felli L. Conservative treatment of ankle osteoarthritis: can platelet-rich plasma effectively postpone surgery? J Foot Ankle Surg 2017;56:362–5.
32. Paget LD, Reurink G, de Vos RJ, Weir A, Moen MH, Bierma-Zeinstra SM, et al. Effect of platelet-rich plasma injections vs placebo on ankle symptoms and function in patients with ankle osteoarthritis: a randomized clinical trial. JAMA 2021;326:1595–605.
33. Godoy-Santos AL, Fonseca LF, de Cesar Netto C, Giordano V, Valderrabano V, Rammelt S. Ankle osteoarthritis. Rev Bras Ortop (Sao Paulo) 2020;56:689–96.
34. Vannabouathong C, Del Fabbro G, Sales B, Smith C, Li CS, Yardley D, et al. Intra-articular injections in the treatment of symptoms from ankle arthritis: a systematic review. Foot Ankle Int 2018;39:1141–50.
35. Derwich M, Mitus-Kenig M, Pawlowska E. Interdisciplinary approach to the temporomandibular joint osteoarthritis-review of the literature. Medicina (Kaunas) 2020;56:225.
36. Zotti F, Albanese M, Rodella LF, Nocini PF. Platelet-rich plasma in treatment of temporomandibular joint dysfunctions: narrative review. Int J Mol Sci 2019;20:277.
37. Li FL, Wu CB, Sun HJ, Zhou Q. Comparison of autologous platelet-rich plasma and chitosan in the treatment of temporomandibular joint osteoarthritis: a retrospective cohort study. J Oral Maxillofac Surg 2021;79:324–32.
38. Sousa BM, López-Valverde N, López-Valverde A, Caramelo F, Fraile JF, Payo JH, et al. Different treatments in patients with temporomandibular joint disorders: a comparative randomized study. Medicina (Kaunas) 2020;56:113.
39. Bousnaki M, Bakopoulou A, Koidis P. Platelet-rich plasma for the therapeutic management of temporomandibular joint disorders: a systematic review. Int J Oral Maxillofac Surg 2018;47:188–98.
40. Haigler MC, Abdulrehman E, Siddappa S, Kishore R, Padilla M, Enciso R. Use of platelet-rich plasma, platelet-rich growth factor with arthrocentesis or arthroscopy to treat temporomandibular joint osteoarthritis: systematic review with meta-analyses. J Am Dent Assoc 2018;149:940–52.
41. Knezevic NN, Candido KD, Vlaeyen JW, Van Zundert J, Cohen SP. Low back pain. Lancet 2021;398:78–92.
42. Chou R. Low back pain. Ann Intern Med 2021;174:ITC113-28.
43. Xuan Z, Yu W, Dou Y, Wang T. Efficacy of platelet-rich plasma for low back pain: a systematic review and meta-analysis. J Neurol Surg A Cent Eur Neurosurg 2020;81:529–34.
44. Sanapati J, Manchikanti L, Atluri S, Jordan S, Albers SL, Pappolla MA, et al. Do regenerative medicine therapies provide long-term relief in chronic low back pain: a systematic review and metaanalysis. Pain Physician 2018;21:515–40.
45. Schneider BJ, Hunt C, Conger A, Qu W, Maus TP, Vorobeychik Y, et al. The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review. Spine J 2022;22:226–37.
46. Jain D, Goyal T, Verma N, Paswan AK, Dubey RK. Intradiscal platelet-rich plasma injection for discogenic low back pain and correlation with platelet concentration: a prospective clinical trial. Pain Med 2020;21:2719–25.
47. Baig MZ, Abdullah UE, Muhammad A, Aziz A, Syed MJ, Darbar A. Use of platelet-rich plasma in treating low back pain: a review of the current literature. Asian Spine J 2021;15:117–26.
48. Urits I, Viswanath O, Galasso AC, Sottosani ER, Mahan KM, Aiudi CM, et al. Platelet-rich plasma for the treatment of low back pain: a comprehensive review. Curr Pain Headache Rep 2019;23:52.
49. Wu J, Zhou J, Liu C, Zhang J, Xiong W, Lv Y, et al. A prospective study comparing platelet-rich plasma and local anesthetic (LA)/corticosteroid in intra-articular injection for the treatment of lumbar facet joint syndrome. Pain Pract 2017;17:914–24.
50. Mohammed S, Yu J. Platelet-rich plasma injections: an emerging therapy for chronic discogenic low back pain. J Spine Surg 2018;4:115–22.
51. Nowak Z, Chęciński M, Nitecka-Buchta A, Bulanda S, Ilczuk-Rypuła D, Postek-Stefańska L, et al. Intramuscular injections and dry needling within masticatory muscles in management of myofascial pain: systematic review of clinical trials. Int J Environ Res Public Health 2021;18:9552.
52. Sakalys D, Rokicki JP, Januzis G, Kubilius R. Plasma rich in growth factors injection effectiveness for myofascial pain treatment in masticatory muscles: randomised controlled trial. J Oral Rehabil 2020;47:796–801.
53. Yilmaz O, Sivrikaya EC, Taskesen F, Pirpir C, Ciftci S. Comparison of the efficacy of botulinum toxin, local anesthesia, and platelet-rich plasma injections in patients with myofascial trigger points in the masseter muscle. J Oral Maxillofac Surg 2021;79:88.
54. Scott A, Docking S, Vicenzino B, Alfredson H, Murphy RJ, Carr AJ, et al. Sports and exercise-related tendinopathies: a review of selected topical issues by participants of the second International Scientific Tendinopathy Symposium (ISTS) Vancouver 2012. Br J Sports Med 2013;47:536–44.
55. Li A, Wang H, Yu Z, Zhang G, Feng S, Liu L, et al. Platelet-rich plasma vs corticosteroids for elbow epicondylitis: a systematic review and meta-analysis. Medicine (Baltimore) 2019;98e18358.
56. Arirachakaran A, Sukthuayat A, Sisayanarane T, Laoratanavoraphong S, Kanchanatawan W, Kongtharvonskul J. Platelet-rich plasma versus autologous blood versus steroid injection in lateral epicondylitis: systematic review and network meta-analysis. J Orthop Traumatol 2016;17:101–12.
57. Tosti R, Jennings J, Sewards JM. Lateral epicondylitis of the elbow. Am J Med 2013;126:357.
58. Hardy R, Tori A, Fuchs H, Larson T, Brand J, Monroe E. To improve pain and function, platelet-rich plasma injections may be an alternative to surgery for treating lateral epicondylitis: a systematic review. Arthroscopy 2021;37:3360–7.
59. Galatz LM, Gerstenfeld L, Heber-Katz E, Rodeo SA. Tendon regeneration and scar formation: the concept of scarless healing. J Orthop Res 2015;33:823–31.
60. Chen XT, Fang W, Jones IA, Heckmann ND, Park C, Vangsness CT Jr. The efficacy of platelet-rich plasma for improving pain and function in lateral epicondylitis: a systematic review and meta-analysis with risk-of-bias assessment. Arthroscopy 2021;37:2937–52.
61. Varshney A, Maheshwari R, Juyal A, Agrawal A, Hayer P. Autologous platelet-rich plasma versus corticosteroid in the management of elbow epicondylitis: a randomized study. Int J Appl Basic Med Res 2017;7:125–8.
62. Kemp JA, Olson MA, Tao MA, Burcal CJ. Platelet-rich plasma versus corticosteroid injection for the treatment of lateral epicondylitis: a systematic review of systematic reviews. Int J Sports Phys Ther 2021;16:597–605.
63. Muthu S, Patel S, Selvaraj P, Jeyaraman M. Comparative analysis of leucocyte poor vs leucocyte rich platelet-rich plasma in the management of lateral epicondylitis: systematic review & meta-analysis of randomised controlled trials. J Clin Orthop Trauma 2021;19:96–107.
64. Simental-Mendía M, Vilchez-Cavazos F, Álvarez-Villalobos N, Blázquez-Saldaña J, Peña-Martínez V, Villarreal-Villarreal G, et al. Clinical efficacy of platelet-rich plasma in the treatment of lateral epicondylitis: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Clin Rheumatol 2020;39:2255–65.
65. Chen X, Jones IA, Park C, Vangsness CT Jr. The efficacy of platelet-rich plasma on tendon and ligament healing: a systematic review and meta-analysis with bias assessment. Am J Sports Med 2018;46:2020–32.
66. Ling Y, Wang S. Effects of platelet-rich plasma in the treatment of plantar fasciitis: a meta-analysis of randomized controlled trials. Medicine (Baltimore) 2018;97e12110.
67. Hurley ET, Shimozono Y, Hannon CP, Smyth NA, Murawski CD, Kennedy JG. Platelet-rich plasma versus corticosteroids for plantar fasciitis: a systematic review of randomized controlled trials. Orthop J Sports Med 2020;8:2325967120915704.
68. Hosny N, Goubran F, BadrEldin Hasan B, Kamel N. Assessment of vascular endothelial growth factor in fresh versus frozen platelet rich plasma. J Blood Transfus 2015;2015:706903.
69. Alkhatib N, Salameh M, Ahmed AF, Alkaramany E, Ahmed G, Mekhaimar MM, et al. Platelet-rich plasma versus corticosteroids in the treatment of chronic plantar fasciitis: a systematic review and meta-analysis of prospective comparative studies. J Foot Ankle Surg 2020;59:546–52.
70. Fei X, Lang L, Lingjiao H, Wei C, Zhou X. Platelet-rich plasma has better mid-term clinical results than traditional steroid injection for plantar fasciitis: a systematic review and meta-analysis. Orthop Traumatol Surg Res 2021;107:103007.
71. Chiew SK, Ramasamy TS, Amini F. Effectiveness and relevant factors of platelet-rich plasma treatment in managing plantar fasciitis: a systematic review. J Res Med Sci 2016;21:38.
72. Christian RA, Rossy WH, Sherman OH. Patellar tendinopathy: recent developments toward treatment. Bull Hosp Jt Dis (2013) 2014;72:217–24.
73. Liddle AD, Rodríguez-Merchán EC. Platelet-rich plasma in the treatment of patellar tendinopathy: a systematic review. Am J Sports Med 2015;43:2583–90.
74. Kon E, Filardo G, Di Martino A, Marcacci M. Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use. Knee Surg Sports Traumatol Arthrosc 2011;19:516–27.
75. Tschon M, Fini M, Giardino R, Filardo G, Dallari D, Torricelli P, et al. Lights and shadows concerning platelet products for musculoskeletal regeneration. Front Biosci (Elite Ed) 2011;3:96–107.
76. de Mos M, van der Windt AE, Jahr H, van Schie HT, Weinans H, Verhaar JA, et al. Can platelet-rich plasma enhance tendon repair?: a cell culture study. Am J Sports Med 2008;36:1171–8.
77. Smith J, Sellon JL. Comparing PRP injections with ESWT for athletes with chronic patellar tendinopathy. Clin J Sport Med 2014;24:88–9.
78. Dupley L, Charalambous CP. Platelet-rich plasma injections as a treatment for refractory patellar tendinosis: a meta-analysis of randomised trials. Knee Surg Relat Res 2017;29:165–71.
79. Vetrano M, Castorina A, Vulpiani MC, Baldini R, Pavan A, Ferretti A. Platelet-rich plasma versus focused shock waves in the treatment of jumper’s knee in athletes. Am J Sports Med 2013;41:795–803.
80. Unlu MC, Kivrak A, Kayaalp ME, Birsel O, Akgun I. Peritendinous injection of platelet-rich plasma to treat tendinopathy: a retrospective review. Acta Orthop Traumatol Turc 2017;51:482–7.
81. Fahy KE, Miller EM, Kobayashi Y, Gottschalk AW. Efficacy of platelet-rich plasma on symptom reduction in patellar tendinopathy. Ochsner J 2021;21:232–4.
82. Andriolo L, Altamura SA, Reale D, Candrian C, Zaffagnini S, Filardo G. Nonsurgical treatments of patellar tendinopathy: multiple injections of platelet-rich plasma are a suitable option: a systematic review and meta-analysis. Am J Sports Med 2019;47:1001–18.
83. Dadgostar H, Fahimipour F, Pahlevan Sabagh A, Arasteh P, Razi M. Corticosteroids or platelet-rich plasma injections for rotator cuff tendinopathy: a randomized clinical trial study. J Orthop Surg Res 2021;16:333.
84. Dickinson RN, Ayers GD, Archer KR, Fan R, Page C, Higgins LD, et al. Physical therapy versus natural history in outcomes of rotator cuff tears: the Rotator Cuff Outcomes Workgroup (ROW) cohort study. J Shoulder Elbow Surg 2019;28:833–8.
85. Lo IK, Denkers MR, More KD, Nelson AA, Thornton GM, Boorman RS. Partial-thickness rotator cuff tears: clinical and imaging outcomes and prognostic factors of successful nonoperative treatment. Open Access J Sports Med 2018;9:191–7.
86. Lin MT, Chiang CF, Wu CH, Huang YT, Tu YK, Wang TG. Comparative effectiveness of injection therapies in rotator cuff tendinopathy: a systematic review, pairwise and network meta-analysis of randomized controlled trials. Arch Phys Med Rehabil 2019;100:336–49.
87. Zhou Y, Wang JH. PRP treatment efficacy for tendinopathy: a review of basic science studies. Biomed Res Int 2016;2016:9103792.
88. Chen X, Jones IA, Togashi R, Park C, Vangsness CT Jr. Use of platelet-rich plasma for the improvement of pain and function in rotator cuff tears: a systematic review and meta-analysis with bias assessment. Am J Sports Med 2020;48:2028–41.
89. A Hamid MS, Sazlina SG. Platelet-rich plasma for rotator cuff tendinopathy: a systematic review and meta-analysis. PLoS One 2021;16e0251111.
90. Giovannetti de Sanctis E, Franceschetti E, De Dona F, Palumbo A, Paciotti M, Franceschi F. The efficacy of injections for partial rotator cuff tears: a systematic review. J Clin Med 2020;10:51.
91. Lin MT, Wei KC, Wu CH. Effectiveness of platelet-rich plasma injection in rotator cuff tendinopathy: a systematic review and meta-analysis of randomized controlled trials. Diagnostics (Basel) 2020;10:189.
92. Kelley MJ, McClure PW, Leggin BG. Frozen shoulder: evidence and a proposed model guiding rehabilitation. J Orthop Sports Phys Ther 2009;39:135–48.
93. Thu AC, Kwak SG, Shein WN, Htun M, Htwe TT, Chang MC. Comparison of ultrasound-guided platelet-rich plasma injection and conventional physical therapy for management of adhesive capsulitis: a randomized trial. J Int Med Res 2020;48:300060520976032.
94. El-Sharkawy H, Kantarci A, Deady J, Hasturk H, Liu H, Alshahat M, et al. Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J Periodontol 2007;78:661–9.
95. Karabaş Ç, Talay Çalış H, Topaloğlu US, Karakükçü Ç. Effects of platelet-rich plasma injection on pain, range of motion, and disability in adhesive capsulitis: a prospective, randomized-controlled study. Turk J Phys Med Rehabil 2021;67:462–72.
96. Barman A, Mukherjee S, Sahoo J, Maiti R, Rao PB, Sinha MK, et al. Single intra-articular platelet-rich plasma versus corticosteroid injections in the treatment of adhesive capsulitis of the shoulder: a cohort study. Am J Phys Med Rehabil 2019;98:549–57.
97. Shahzad HF, Taqi M, Gillani SF, Masood F, Ali M. Comparison of functional outcome between intra-articular injection of corticosteroid versus platelet-rich plasma in frozen shoulder: a randomized controlled trial. Cureus 2021;13e20560.
98. Kearney RS, Ji C, Warwick J, Parsons N, Brown J, Harrison P, et al. Effect of platelet-rich plasma injection vs sham injection on tendon dysfunction in patients with chronic midportion Achilles tendinopathy: a randomized clinical trial. JAMA 2021;326:137–44.
99. Moraes VY, Lenza M, Tamaoki MJ, Faloppa F, Belloti JC. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev 2014;2014:CD010071.

Article information Continued

Table 1.

Growth factors contained in platelet-rich plasma and their major physiological actions

Growth factor Physiological action
Transforming growth factor-β Enhances undifferentiated mesenchymal cell proliferation
Modulates endothelial, fibroblastic, and osteoblastic mitogenesis
Modulates collagen synthesis and collagenase secretion
Modulates mitogenic effects of other growth factors
Enhances endothelial chemotaxis and angiogenesis
Inhibits macrophage and lymphocyte proliferation
Fibroblast growth factor Enhances growth and differentiation of chondrocytes and osteoblasts
Mitogenic for mesenchymal cells, chondrocytes, and osteoblasts
Platelet-derived growth factor A and B Mitogenic for mesenchymal cells and osteoblasts
Promotes chemotaxis and mitogenesis in fibroblast, glial, or smooth muscle cells
Modulates collagenase secretion and collagen synthesis
Promotes macrophage and neutrophil chemotaxis
Epidermal growth factor Enhances endothelial chemotaxis or angiogenesis
Modulates collagenase secretion
Enhances epithelial or mesenchymal mitogenesis
Vascular endothelial growth factor Stimulates angiogenesis and vessel permeability
Enhances mitogenesis for endothelial cells
Connective tissue growth factor Stimulates angiogenesis
Cartilage regeneration
Fibrosis and platelet adhesion
Insulin-like growth factor 1 and 2 Chemotactic for fibroblasts and stimulates protein synthesis
Stimulates bone formation
Platelet factor 4 Promotes the initial influx of neutrophils into wounds
Chemoattractant for fibroblasts
Interleukin-8 Proinflammatory mediator
Recruitment of inflammatory cells
Keratinocyte growth factor Stimulates endothelial cell growth, migration, adhesion, and survival

Reproduced from Dhillion et al. [19] according to the Creative Commons License.