Platelet-rich Plasma Therapy for Back Pain:  Promise or Hype?

George Rappard, MD

     Platelet-rich plasma (PRP) is a potentially promising biologic therapy that has found itself in great demand recently, fueled by success stories of celebrity recipients and physician willingness to engage in this new therapy.  Demand has also fueled, quite appropriately, scientific investigation.  As a result PRP finds itself in the position of being both highly sought after and also highly scrutinized.  It is also widely available.  As a result, it’s relatively inexpensive and easy to produce.  While PRP holds substantial promise; demand, availability and adoption should keep pace with scientific validation.

     PRP has been in the news and the internet quite a bit.  A virtual who’s who of well-known athletes such as Tiger Woods, Peyton Manning, Cliff Lee, Kobe Bryant and Rafael Nudal have all had PRP treatments.  PRP has been endorsed by the NBA, NFL and MLB.  This sports celebrity A-list has naturally fueled demand by prospective patients willing to pay cash for the high end treatments that professional athletes have access to. 

     PRP is very simple in composition and collection.  PRP is a reversal of the normal 93%: 6% ratio of platelets: red blood cells (RBC).  PRP is also concentrated.  While the normal platelet concentration in plasma is 200,000/ul, to be efficacious PRP is concentrated by at least a factor of 4 (1).  The PRP is produced by collecting a patient’s own blood through a large bore needle so as not to denature the platelets.  The blood is placed in an FDA approved device and centrifuged.  The blood is then separated into platelet poor plasma, RBC and PRP.  Roughly 30cc’s of blood will yield 3cc’s of PRP.  Because PRP isnot heavily processed, it’s not a drug.  While the devices that concentrate it are FDA regulated, its human use is not.

     PRP’s contents and potential mechanisms of action are far more complex than its production and composition.  Platelets contain alpha granules that can release a host of biologically active substances, including IGF-1, TGF, VGEF, PDGF, EGF and Vitranectin.  These factors are involved in cell aggregation, cellular proliferation, angiogenesis and proteoglycan and glycosamine synthesis.  Platelets also contain dense granules rich in Adenosisne, Seratonin, Histamine and Calcium.  These molecules are felt to be cytoprotective, increase vascular permeability and vasodilation and effect cellular migration and remodeling.  In order for platelets to release the biologically complex contents of their granules they have to be activated.  Naturally occurring in-vivo activation is mimicked by activating platelets with thrombin, +/- Calcium chloride.  At least one author has investigated the activation of platelets in PRP with autologous serum (2). 

     PRP has been a focus of scientific study.   Currently, clinicaltrials.gov lists 94 ongoing research studies.  A search of PRP therapy on PubMed lists 2,385 citations.  This suggests that science may be catching up to demand and availability in some new and emerging applications of PRP.   PRP has been studied in the areas of wound healing, epichondylitis, plantar fasciitis, Achilles tendinopathy, total knee arthroplasty, rotator cuff injury and non-healing long bone fractures, with mixed results.  PRP has been found to be efficacious for the treatment of non-healing skin wounds (3; 4).  In a small, non-randomized study, PRP was shown to be effective in treating epicondylitis, a painful condition of the elbow (5).  More recently, a large randomized trial presented at the 2013 American Academy of Orthopedic Surgery Annual Meeting validated the effectiveness of PRP in treating epicondylitis, or tennis elbow.  The randomized trial enrolled 230 patients and is the largest study to date on PRP.  84% of patients treated with PRP met with success (6).  A small pilot study showed potential effectiveness in treating plantar fasciitis, a painful condition of the foot (7). The American Academy of Orthopedic Surgeons has tackled the interest in PRP by publishing a series of reviews in the Academy bulletin, AAOS Now.  PRP was reported to not be effective in the treatment of rotator cuff injuries in the shoulder or anterior cruciate ligament injuries of the knee (8; 9).  PRP was found to be a promising therapy for non-healing long bone fractures and the treatment of Achilles tendinopathy of the ankle (10; 11). 

         The use of PRP for the treatment of back pain has not been well studied clinically.  A  PubMed search reveals no cited studies for the use of PRP as an injection for painful lumbar facet joints or sacroiliac joints, yet a quick Google search reveals that there is no paucity of practitioners willing to perform these injections.  Similar results were noted for PRP injection of spinal or sacroiliac ligaments. 

     PRP has been studied in the lumbar disc, though this area remains highly investigational.  A search of clinicaltrials.gov reveals 1 human study-not enrolling patients however.  Animal studies have shown promise.  Gullung at al studied the effects of PRP on degenerative discs by studying its effects on the L4/5 discs of Sprague-Dawley rats using a 21 gage needle disc injury model (12). The investigators found that the PRP treated discs had a significantly improved disc height over controls.  Histological analysis showed that there was preservation of disc architecture compared to controls.  Additionally, on MRI analysis there was inproved disc fluid content.  The authors concluded that PRP may confer protective and even regenerative effects in this animal injury model.  Obata et al used a disc puncture model to study the effects of PRP on rabbits (2).  The authors found that the PRP treated animals had significantly increased disc height over controls and significantly increased chondrocytes seen in the injured discs on histological analysis.  No difference was seen in T2 MR analysis of the discs between treated and sham groups.  Lastly, Chen et al studied the use of PRP in a chymopapain disc injury porcine model (13).  In the PRP group an increase in mRNA involved in chondrogenesis and matrix accumulation was noted.  Increased disc height was also noted over controls.

     The only area in spine where PRP has been extensively studied in humans is in its use as an adjunct to promote fusion in surgery.  Here the anticipated results, based on the bioactivity of PRP, were not always reproducible.  2 studies of patients undergoing lumbar fusion surgery have found an increased non-union (poor bone healing) rate in patients treated with PRP and bone graft vs. bone graft alone (14; 15).  Other studies have found similar or improved rates of fusion (bone healing) in patients treated with PRP (16; 17).  This represents a very illustratable example of excitement overrunning scientific caution.  Prior to these studies physicians performing fusions were rapidly adopting PRP to augment fusion rates based solely on its potential biological mechanism.

     There are several variables that should be considered and investigated prior to moving on to human PRP studies for spine pain.  PRP, as studied and reported, is very heterogenous. Many papers do not quantify the platelet concentration used.  As a result, there is little or no experience with dose related effects.  Also, studies use different activators, whether Calcium Chloride, thrombin or plasma, potentially confounding results.  Furthermore, some formulations contain white blood cells, while others do not.  The contribution of white blood cells to PRP’s potentially therapeutic effects are not well understood.  Lastly, caution should be taken when studying any substance that requires a disc puncture.  Human and animal studies alike have already validated the potential for needle based disc punctures to result in accelerated disc degeneration (2; 12; 18).

     Despite the lack of validated human data to promote the use of PRP in treating spine pain, it’s availability and ease of production, lack of regulation, public demand and willingness of practitioners to administer it have created an extensive cash based cottage industry.  Like most drugs and devices, experience and investigation will show that there is no PRP related “Holy Grail” for the treatment of spinal pain or musculoskeletal injury.  Rather, there are and will be some applications that are better than others and probably some applications that should be avoided all together.  The use of PRP injected intramuscularly (where it can cause muscle fibrosis) and the use of PRP in fusion surgery (where it can actually result in lower fusion rates) are examples of potentially good applications based on biological mechanism that were not borne out scientifically.  While the study of PRP and other biologics for the treatment of spinal pain is reasonable and in fact supported by animal data, widespread use without scientific validity is not and restraint should be exercised.

1. Marx, R and Garg A. Dental and craniofacial applications of platelet rich plasma. Quintessence publishing company Inc, 2005.

2. Obata S et al. Effect of autologous platelet-rich plasma-releasate on intervertebral disc degeneration in the rabbit annular puncture model: A preclinical study. Arthritis research & Therapy, Nov 2012, Vol. 14, p. R241.

3. Crovetti G et al. Platelet gel for healing cutaneous chronic wounds.  Transfus Apher Sci, 2004. Vol. 30, pp. 145-51.

4. McAleer JP, Kaplan E, Persich G. Efficacy of concentrated autologous platelet-derived growth factors in chronic lower extremity wounds. J Am Podiatr Med Assoc, Vol. 96, pp. 482-8.

5. Edwards SG, Calandruccio JH. Autologous blood injections for refractory lateral epicondylitis. 2003, Am J Hand Surg, Vol. 28, pp. 272-8.

6. Platelet Rich Plasma Significantly Improves Clinical Outcomes in Patients with Chronic Tennis Elbow (abstract). Mishra AK, Skrepnik NV, Edwards, SG et al. Chicago. Proceedings of the 2013 annual meeting of the American Academy of Orthopedic Surgery.

7. Barrett S, Erredge S. Growth factors for chronic plantar fascitis. 2004, Podiatry Today, Vol. 17, pp. 37-42.

8. PRP does not improve rotator cuff healing. AAOS Now. April 2011.

9. Stanton, T. PRP shows little benefit in ACL reconstruction at 6 months. AAOS Now. April 2010.

10. Stanton, T. High-concentrate PRP Promotes Healing in Long-Bone. AAOS Now. February 2010.

11. Leahy, M. PRP effective in treating chronic Achilles tendinosis. AAOS Now. March 2010.

12. Gullung G et al. Platelet-rich plasma effects on degenerative disc disease: analysis of histology and imaging in an animal model. Evidence-Based Spine-Care Journal. 2011, Vol. 21, 4, pp. 13-18.

13. Chen WH et al. Intervertebral dsic regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biometerials. Oct 2009, Vol. 29, pp. 5523-33.

14. Carreon LY et al. Platelet gel (AGF) fails to increase fusion rates in instrumented posterolateral fusions. Spine. 2009, Vol. 30, 9, pp. E243-7.

15. Weiner BK, Walker M. Efficacy of autologous growth factors in autologous intertransverse fusions. Spine. 2003, Vol. 28, pp. 1968-70.

16. Jenis LG, Banco RJ, Kwon B. A prospective study of Autologous Growth Factors (AGF) in lumbar interbody fusion. Spine J. 2006, Vol. 6, 1, pp. 14-20.

17. Hee HT et al. Do autologous growth factors enhance transforaminal lumbar interbody fusion? Eur Spine J. 2003, Vol. 12, 12, pp. 400-7.

18.  Carragee EJ et al.  2009 ISSLS prize winner:  Does discography cause accelerated progression of degenerative changes in the lumbar disc.  Spine.  2009.  Vol. 34, 12 pp 2338-45