1 Practical PAIN MANAGEMENT, January/February 2008©2008 PPM Communications, Inc. Reprinted with permission.

Platelet Rich Plasma (PRP) grafting techniques are nowbeing utilized in musculoskeletal medicine with increas-ing frequency and effectiveness. Soft tissue injuries treat-

ed with PRP include tendonopathy, tendonosis, acute and chron-ic muscle strain, muscle fibrosis, ligamentous sprains, and jointcapsular laxity. PRP has also been utilized to treat intra-articu-lar injuries. Examples include arthritis, arthrofibrosis, articularcartilage defects, meniscal injury, and chronic synovitis or jointinflammation.

Platelet Rich Plasma was first used in cardiac surgery by Fer-rari et al. in 1987 as an autologous transfusion component afteran open heart operation to avoid homologous blood producttransfusion.1 It is now being utilized by musculoskeletal (MSK)providers following the effective use in multiple specialties. PRPhas also been successfully used in various specialties such as max-illofacial, cosmetic, spine, orthopedic, podiatric and for gener-al wound healing.2,3

MSK practitioners began using PRP for tendonosis and ten-donitis in the early 1990s.4 PRP techniques have most common-ly been applied by MSK practitioners previously trained in theuse of—and on the knowledge backbone of—prolotherapy. Al-though there is a paucity of well designed, randomized trials forits use in MSK medicine, animal studies, case reports, and anec-dotal evidence suggests that this technique will continue to de-velop as a way to regenerate tissue that has lost its inherent home-ostasis and thereby relieve associated pain and dysfunction.

Standardizing the Nomenclature for PRPThe authors define a PRP Matrix Graft as follows:

A tissue graft incorporating autologous growth factors and/ or au-tologous undifferentiated cells in a cellular matrix whose design dependson the receptor site and tissue of regeneration.

In reading the literature, different verbiage will arise, such as

platelet leukocyte gel, platelet rich plasma gel, platelet concen-trate, blood plasma therapy, etc. When examining the literature,one must evaluate whether concentrations of platelets, nucleat-ed cells, growth factors, fibrin, and platelet activation is meas-ured. These factors— along with skillful percutaneous injectionand surgical techniques—all contribute to the effectiveness oftherapy.5 Everts, on reviewing 28 human studies, found thatseven showed either no benefit or negative effects of PRP.3 How-ever, when these studies were reviewed, many had very smallsample sizes (as few as three patients) and several had plateletportions that had been activated prior to use via differing means.Hopefully, in the near future, the nomenclature will benefit fromsome form of standardization. It is the authors’ experience, how-ever, that the wording of ‘graft’ is required in the nomenclaturefor third party reimbursement reasons, as well as to accuratelydescribe how this modality is actually utilized at present in theclinic and surgical settings.

For our purposes, we will consider PRP gel as PRP that is ac-tivated with either autologous thrombin and calcium, bovinethrombin and calcium, or thrombin alone. Autologous PRP gelstipulates the use of autologous thrombin. The author consid-ers a PRP Matrix Graft to include gel or no gel. This must bestipulated at the time of treatment. Again, the tissue of treat-ment will demand what matrix, if any, is added or utilized.

Constituents and Properties of an Effective Regenerative GraftNormal tissue homeostasis is maintained in a prescribed physio-logic manner. These stages will be reviewed from a hypotheticaltime of injury through the healing phase to understand how tomaximize PRP graft matrix preparation. Platelets contain twounique types of granules—the alpha-granules and dense granules.

Alpha-granules contain a variety of hemostatic proteins (co-agulation proteins), as well as growth factors, cytokines,

Platelet Rich Plasma(PRP) Matrix GraftsPRP application techniques in musculoskeletal medicine utilize the concentrated healing components of a patient's own blood—reintroducedinto a specific site—to regenerate tissue and speed the healing process.

By David Crane, MD and Peter A.M. Everts, PhD

P l a t e l e t R i c h P l a s m a ( P R P ) M a t r i x G r a f t s

chemokines (pro-inflammatory activation-inducible cytokines)and other proteins such as adhesion proteins.6 Of primary in-terest to the clinician are the three adhesion molecules and sevengrowth factors present in the alpha granule.7

Dense granules contain factors that promote platelet aggre-gation (ADP, calcium, serotonin). Cell activation of plateletscauses the discharge of granule contents. In other words,platelets require activation in order to begin the cascade ofevents that lead to collagen restoration and growth. This acti-vation must occur at the tissue level (where the platelets aggre-gate and adhere to collagen at the site of grafting).5

A synopsis of the various growth factors in PRP, together withtheir source and function, is presented in Table 1.

A PRP Matrix Graft is made in a clinical or operative settingby using one of the several available table-top machines on themarket. Several authors offer reviews of available graft prepa-ration centrifuges and their ability to concentrate growth fac-tors.2,3,8 Each machine has a separate, disposable unit that con-centrates platelets in a small amount of plasma. A thin layer ofplatelets is found immediately above the leukocytes in the buffycoat of centrifuged blood. When a concentrated platelet por-tion is made, the buffy coat containing elevated levels of leuko-cytes—along with concentrated platelets—are suspended in asmall amount of plasma for subsequent grafting. The clinicianhopes that the platelets are not activated and remain suspend-ed until grafting and contact with thrombin or collagen occurs.

Necessary Stages of HealingNormal platelet activation leads to three necessary stages ofhealing: Inflammation, Proliferation, and Remodeling.9 Thecellular components involved in the three phases of healing are

depicted in Figure 1. If any of these stages are incomplete—orif they proceed unabated—tissue homeostasis is lost and painand loss of function may result. Most reviews on this topic focuson only the growth factors contained within the alpha granuleof the platelet which is released upon platelet activation. It isimportant to understand, however, that if the platelets aren’tsuspended with biologic levels of other constituents of plasma—such as leukocytes, cytokines, and fibrin (the matrix)—the graftis either not effective or less effective.3 If fibrin levels are toohigh, or platelet activation occurs prior to collagen binding, thegraft is also inhibited. Other functions of platelet activation andthe subsequent cascade of events that occur include cytokine sig-naling, chemokine release, and mitogenesis.9

2Practical PAIN MANAGEMENT, January/February 2008©2008 PPM Communications, Inc. Reprinted with permission.

TABLE 1. Synopsis of growth factors present in PRP From Peter A.M. Everts et al. Platelet-Rich Plasma and Platelet Gel: A Review3

TABLE 1. SYNOPSIS OF GROWTH FACTORS PRESENT IN PRP

Growth Factor Source Function

Transforming GrowthFactor-beta,TGF-ß

Platelets, extracellular matrixof bone, cartilage matrix,activated TH1 cells and natu-ral killer cells, macrophages/monocytes and neutrophils

Stimulates undifferentiated mesenchymal cell proliferation; regulatesendothelial, fibroblastic and osteoblastic mitogenesis; regulates colla-gen synthesis and collagenase secretion; regulates mitogenic effectsof other growth factors; stimulates endothelial chemotaxis and angio-genesis; inhibits macrophage and lymphocyte proliferation

Basic FibroblastGrowth Factor,bFGF

Platelets, macrophages,mesenchymal cells, chon-drocytes, osteoblasts

Promotes growth and differentiation of chondrocytes and osteoblasts;mitogenetic for mesenchymal cells, chondrocytes and osteoblasts

Platelet DerivedGrowthFactor,PDGFa-b

Platelets, osteoblasts,endothelial cells,macrophages, monocytes,smooth muscle cells

Mitogenetic for mesenchymal cells and osteoblasts; stimulates chemo-taxis and mitogenesis in fibroblast/glial/smooth muscle cells; regulatescollagenase secretion and collagen synthesis; stimulates macrophageand neutrophil chemotaxis

Epidermal GrowthFactor,EGF

Platelets, macrophages,monocytes

Stimulates endothelial chemotaxis/angiogenesis; regulates collagenasesecretion; stimulates epithelial/mesenchymal mitogenesis

Vascular endothelialgrowth factor,VEGF

Platelets, endothelial cells Increases angiogenesis and vessel permeability, stimulates mitogene-sis for endothelial cells

Connective tissuegrowth factor,CTGF

Platelets through endocyto-sis from extracellular envi-ronment in bone marrow.

Promotes angiogenesis, cartilage regeneration, fibrosis and plateletadhesion

FIGURE 1. The physiology of healing of the chronic wound. From: emed-icine.com.15 Used with permission.

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Inflammatory PhaseDuring the inflammatory phase, the functions of activatedplatelets include:

• Anti-microbial• Adhesion• Aggregation• Clot retraction• Pro-coagulation• Cytokine signaling• Chemokine release• Growth factor releaseThere is now evidence to suggest that at certain concentra-

tions, or dose response curves, platelet rich plasma grafts maybe anti-inflammatory or pro-inflammatory in certain tissues.10 Adose response relationship exists to a currently unknown levelof PRP concentration and ensuing migration and proliferationof progenitor stem cells at the tissue injury site11 (see Figure 2).

There is emerging evidence to suggest that PRP grafts in thefour- to six-fold range (106 platelets) have more anti-inflamma-tory mediators and effects and are clinically relevant and usefulfor most situations. PRP grafts in the eight- to thirteen-foldrange may be pro-inflammatory in nature.10 Further elucidationof this effect is required, however, as some studies showed ben-eficial effects of higher concentrations of PRP.12

Hesham El-Sharkawy et al. evaluated this effect in periodon-tal tissue. The conclusions were that PRP is a rich source ofgrowth factors and promoted significant changes in monocyte-mediated proinflammatory cytokine/chemokine release. LXA4was increased in PRP, suggesting that PRP may suppress cy-tokine release, limit inflammation, and thereby promote tissueregeneration.10

Weibrich et al. observed an advantageous effect with plateletconcentrations of approximately 106/µL. Further, they statethat higher concentrations might have a paradoxically in-hibitory effect.13

Following the initial inflammatory phase, which typically lastsfor two to three days, fibroblasts enter the site and begin theproliferative phase.9 Low pH and low oxygen levels stimulatefibroblast proliferation in the injury site.14 Fibroblasts becomethe most abundant cell by the seventh day. The fibroblasts are

then responsible for deposition of collagen and ground sub-stance. This phase lasts from two to four weeks. As these areprimarily the deficient cells with chronic injury (lack of normalcollagen in extracellular matrix), this stage is mandatory forMSK repair.

The Proliferative PhaseDuring the proliferative phase—peaking anywhere from day 5to 15 and which can last for weeks—fibroblasts differentiate intomyofibroblasts and actin contracts to make the wound smaller.Low pH and hypoxemia also stimulates neovascularization.Neovessels begin to form at approximately day 5 to 7 and thisprocess proceeds until the neovessels disappear near comple-tion of the remodeling phase.

The Remodeling Phase During the remodeling phase, collagen matures and strength-ens. Tissue repair starts when the production and break downof collagen equalizes. This phase can last over one year. Duringthis period, type III collagen is replaced by type I collagen, re-organization occurs, and the blood neovessels disappear.9

Cell Proliferation TriangleIt has become apparent, then, that PRP grafts function via atriad of interactions, known as the cell proliferation triangle16,17

(see Figure 3). Each element of this triangle must be present foreffective tissue repair and pain relief.

When preparing a graft for clinical use, the constituents ofeach of these three must be considered—i.e. is there an inher-ent matrix to place the graft in, or will the graft be washed awaywith motion, synovial fluid, or repeated graft compression ordistraction? Does the patient have an adequate response for in-flammation and is there an adequate quantity of platelets to con-centrate for progenitor cell mitogenesis and proliferation?

Biotensegrity—A Construct for Regeneration of TissueBiotensegrity refers to a dynamic construct of compressive andtensional forces acting on, and through, multiple levels of or-ganization to maintain or repair tissue homeostasis. Biotenseg-rity, then, is a repeated pattern of structural and functional ar-chitecture of all living tissue.19,20

The probable link though all levels of biotensegrity is the vas-cular endothelial system with its regenerative and neuroen-docrine functions as subsequently described.

hMSC Proliferation as a Function of8-day Exposure to Platelet Released Concentrations

900800700600500400300200100

0WholeBlood

PlateletPoor Plasma

1.25x 2.5x 5x 10x(x = increase above native levels)

Quan

tityo

fhMS

C’s

FIGURE 2. Relationship of differing platelet concentrations and humanmesenchymal stem cell (hMSC) migration and proliferation. From:Haynesworth, Stephen et al. Mitogenic Stimulation of Human Mes-enchymal Stem Cells by Platelet Releasate.11 Used with permission.

FIGURE 3. Cell Proliferation Triangle.

Scaffold

UndifferentiatedProgenitor Cells

Signal Proteins andAdhesion Molecules

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Endothelial cells line the lumen of allblood vessels as a single squamous epithe-lial cell layer. They are derived from an-gioblasts and hemangioblasts. Weibel-Palade bodies are specialized secretorygranules found in endothelial cells. Thesevesicles store preformed hormones, cy-tokines, and growth factors; as well as en-zymes, receptors, and adhesion mole-cules; which can be released and/or ex-pressed on the cell surface without denovo protein syntheses by regulated exo-cytosis in response to stimulation of cellactivation.6

Thus, the authors believe there is suffi-cient evidence to suggest that the vascularendothelial system links all of thebiotensegrity levels together as the variousfactors are at work up and down the scale.

Contraindications to the Use of PRP MatrixGrafts3,21,22

Absolute Contraindications include:• Platelet dysfunction syndrome• Critical thrombocytopenia• Hypofibrinogenemia• Hemodynamic instability• Septicemia• Sensitivity to bovine thrombin (if

using bovine thrombin with calciumto make platelet gel)

Relative Contraindications include:• Consistent use (anti-inflammatory

use) of NSAID’s within 48 hours ofprocedure

• Corticosteroid injection at treatmentsite or systemic use of corticosteroidswithin 2 weeks of graft procedure

• Recent fever or illness• Rash at graft donor site or at recep-

tor site• Cancer — especially hematopoetic

or of bone • Active history or history of

Pseudomonas, Enterococcus orKlebsiella infection, as PRP has beenshown in one study to potentiallystimulate these pathogens.22

• HGB <10 g/dl• Platelet count less than 105/µL

Risks Involved With the Use of PRP Matrix GraftsWhile there have been no reports of wors-ened pain or function following tissuematuration that the authors could find,few randomized, placebo controlled trialsexist regarding the utilization of thesegrafts. In the primary author’s experienceof performing approximately 20 to 30

cases of percutaneous PRP Matrix Graftsper week for the last two years, no patientsreported worsened pain or function. It isfelt by the authors—and often expressedin the available literature— that this pro-cedure technique is safe and effective.

Pain at the treatment site is commonfor a short period following injection.One of the primary author’s patients re-ported worsened pain for six months at atreated lateral epicondyle. This subse-quently resolved and has been absent forover one year. This stresses the fact thatremodeling of the tissue is necessary tosee the effects of therapy. No tendon rup-ture or partial rupture was noted and theauthors can find no reports of tendon orligament rupture following PRP. In fact,Olena Virchenko and Per Aspenbergnoted, in a rat achilles tendon transectionmodel, that one postoperative injectionresulted in increased strength after fourweeks. This effect was obliterated with theuse of botox at the site.18

Other risks that may occur at time ofinjection include injury from pain-in-duced syncope. Indeed, the main com-plaint received from patients is the injec-tion pain of the PRP. There is also therisk of limb injury following the graftprocedure since local or regional anes-thesia is used at the time of procedure.The primary author had a patient whostepped from a ladder about four hoursfollowing an achilles and peroneal ten-don injection, with subsequent inversionand fracture of the ankle—most likelydue to proprioceptive and sensory lossfrom anesthesia.

As with any percutaneous needle tech-nique, there is a slight risk of puncturinga hollow organ or infection, but this riskis not expected to be above or below thatof other needle techniques employed inclinical medicine. The accepted risk of in-troduction of infection with percutaneoustechniques has been reported as 1:50,000injections. Since PRP is an autologouspreparation, the risk of introducing for-eign material and the risk of transmissi-ble infection or allergic reaction is effec-tively eliminated—although the entireprocedure must be carried out in sterileconditions. PRP—with its initial inflam-matory phase—is also bacteriocidal, par-ticularly against Stapholococcus aureusand Escherichia coli as shown by Bielec-ki et al.22 The temporary formation ofplatelet and fibrin plugs at the wound sitehas also been noted to prevent the entry

of microorganisms.3,22 However, PRP gelseems to induce the in vitro growth of Ps.aeruginosa, suggesting that it may causean exacerbation of infections with this or-ganism. There was no activity againstKlebsiella pneumoniae or Enterococcusfaecalis.

Other considerations come into play ifthe procedure is not performed with com-pletely autologous preparations. PRP geltechniques that rely upon the use ofbovine thrombin, which may contain con-taminants like bovine Factor Va as aplatelet activation source, may result inantibodies to Factors V and VI, with po-tentially life threatening coagulopathiesresulting.5 Other concerns with bovinethrombin include prion disease, althoughnone are reported in the literature. Theauthors have neither seen nor heard ofany infections occurring with the percu-taneous use of PRP or biocellular thera-peutic grafts.

Regarding the question of carcinogen-esis, growth factors act on cell surface re-ceptors only, do not enter the cell, and donot cause DNA mutation. There is noplausible mechanism by which growth fac-tors would result in neoplastic develop-ment, and there have been no reports ofthis in the literature.3,21 Furthermore,Scott and Pawson showed that growth fac-tors (PGF) activate normal, rather thanabnormal, gene expression.23

Typical Treatment Regimen With PRPConsent

• Average series of injections is two tothree at four- to six-week intervals

• Different sites or areas of treatmentmay expand or contract with furthertreatment

• You must functionally retrain thekinetic chain once the tissue hasundergone some degree of healing

Risks• 1:50,000 chance of introducing

infection with injection procedure • Allergy to local anesthetic(s)• Syncope with pain/blood at the time

of injection• Injury occurence with numbness or

pain following procedure. i.e.falling, ankle sprain with inversion,etc.

• Though extremely rare, pain orfunction may worsen

• Puncture of tissue outside of intend-ed graft site. i.e. vascular, neural,lung, or other tissue placements

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Technique for Myotendinous or Teno-Osseous Sites

• Alcohol or Betadyne prep (we preferBetadyne gel when using an ultra-sound probe for ‘live’ injection guid-ance)

• +/- Ethyl Chloride spray• Inject PRP with approximately 1cc

PRP per cm3 of tissue/interface• Important to touch bone and ‘pep-

per’ the area of teno-osseous junc-tion to stimulate the greatest num-ber of fibroblast colonies

• For myotendinous sites use ultra-sound to ensure layered treatmentthroughout the tendon

• Sterile band-aid applied post injec-tion

• Kinesiotape to protect motion ifneeded

Technique For Intra-Osseous Sites• Alcohol or Betadyne prep (we prefer

Betadyne gel when using an ultra-sound probe for ‘live’ injection guid-ance)

• +/- Ethyl Chloride spray• Local anesthetic either mixed with

the PRP graft or to sites of tender-ness to ‘road test’ the area prior tousing the graft. This ensures that thePRP matrix graft is placed in theproper areas.

• Aspirate degenerative joint fluidprior to PRP matrix graft placement

• Gel the PRP or utilize other stabiliz-ing matrix for intra-articular sites.Ligaments, tendons, and inherentmatrix sites do not require gel in theauthors’ experience

• 8-10cc PRP matrix graft is the typi-cal amount used for a knee or shoul-der joint in our clinic

• “Treat regionally, not locally”(D.Crane, MD; e.g. treat all of the cap-sule that is tender along with tendi-nous and ligamentous sites of ten-derness in addition to the intra-articular capsule)

It should be noted that Kevy and Jacob-son have evaluated the mixture of commonlocal anesthetics with PRP and find no sig-nificant platelet activation or diminutionof graft growth factor functions.7,24

Tendonosis and the Use of PRPAnitua showed—from in vitro studies ofcollagen and tendon—that autologouspreparations rich in growth factors pro-mote proliferation and induce VEGF andHGF production by human tendon cells

in culture.25 Mishra performed an in vitrostudy which determined the effect of aplatelet concentrate medium on the pro-liferation of human skin fibroblasts—thecells responsible for deposition of colla-gen. Buffered PRP was shown to augmenthuman fibroblast proliferation when com-pared to control.26

Schnabel evaluated gene expressionpatterns, DNA, and collagen content ofequine flexor digitorum tendons culturedin a media consisting of PRP and otherblood products. PRP at 100% concentra-tion stimulated the greatest number ofcollagen type I, collagen type III, and car-tilage oligomeric protein (COMP) mole-cule genes without increasing expressionof the pro-inflammatory matrix metallo-proteinases. ELISA detected higher lev-els of PDGF and TGF-B in the PRPgroup.27

Hesham El-Sharkawy et al.10 measuredplatelet derived growth factor (PDGF)-AB,

PDGF-BB, transforming growth factor-b1,insulin-like growth factor-I, fibroblastgrowth factor-basic (FGF-b), epidermalgrowth factor (EGF), vascular endothelialgrowth factor, interleukin-12 (p40/70)and, regulated on activation, normal T-cell expressed and secreted (RANTES) lev-els by enzyme-linked immunosorbentassay. Cytokine, chemokine, and LXA4levels, as well as monocyte chemotactic mi-gration, were analyzed. PRP led to signif-icantly increased levels of growth factorsand significantly suppressed inflamma-tion by promoting secretion of LXA4.

These growth factors stimulated theproliferation of fibroblasts and periodon-tal ligament cells, as well as extracellularmatrix formation, and promoted collagenand total protein synthesis while stimulat-ing the synthesis of hyaluronate from gin-gival fibroblasts. IGF-I levels in PRP inthis study were not significantly differentfrom the cyclolignan picropodophyllin(PPP), suggesting that other cell types

could be responsible for the release of thisgrowth factor.10

Tissue culture studies performed by duToit et al. for use in dermal regenerationconfirmed the potent mitogenic stimula-tion of human fibroblasts, keratinocytes,chondrocytes, neural tissue, and my-oblasts.28

In Vivo Human Studies: Reviews and CaseExamplesTendon and Ligament Use of PRPMishra evaluated 20 patients that failednon-operative treatment for chronic epi-condylar pain. These 20 patients wererandomized to a single PRP injection orinjection with bupivicaine. Mishra com-ments that the IRB would not allow ablood draw from the control patients toblind the study. All PRP patients hadlower pain and greater ROM than control(bupivicaine). Eight weeks after the treat-ment, the platelet-rich plasma patients

noted 60% improvement in their visualanalog pain scores versus 16% improve-ment in control patients. Sixty percent(three of five) of the control subjects with-drew or sought other treatments after the8-week period, preventing further directanalysis. Therefore, only the patientstreated with platelet-rich plasma wereavailable for continued evaluation. At sixmonths, the patients treated with platelet-rich plasma noted 81% improvement intheir visual analog pain scores (P=.0001).At final follow-up (mean, 25.6 months;range, 12-38 months), the platelet-richplasma patients reported 93% reductionin pain compared with before treatment(P<.0001). Of importance, no PRP-treat-ed patient was worse after treatment, andthere were no complications reported inthis study.29

Barrett et al. demonstrated, in a seriesof nine plantar fascia patients, that PRP—with ultrasound guidance—could be safe-ly injected into the medial and central

“Eight weeks after the treatment, the platelet-rich plasma patients

noted 60% improvement in their visual analog pain scores versus

16% improvement in control patients... At 6 months, the patients

treated with platelet-rich plasma noted 81% improvement in their

visual analog pain scores...”

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bands of the most affected plantar fasciawith promising results. Seven out of ninepatients had complete resolution of theirplantar fascial pain at one year and all thepatients in the study had improvementthat was noted on diagnostic ultrasound.One of the patients was considered a fail-ure because of a subsequent steroid injec-tion even though all pain had resolved.30

Scarpone reported on a prospectivestudy carried out in 14 patients with shoul-der pain. The patients all had rotator cufftears with no significant AC joint thicknesswith impingement and no other signifi-cant symptomatic pathology such as labraltears, glenohumeral arthrosis, or gross in-stability. All of the patients failed non-op-erative treatments such as NSAIDs, physi-cal therapy, and corticosteroid injectionsand all were considering surgical options.Of the 14 patients, 12 had statistically sig-nificant improvements in their pain scaleand their strength and endurance at eightweeks. Of the 12 patients, six had radi-ographic evidence of healing of theirtendinopathy on MRI at eight weeks. Ofthe four patients who were consideringsurgery because of persistent pain, onlytwo went on to have rotator cuff surgery.No significant complications were noted.31

Ventura et al. evaluated PRP in ACL re-pair. A total of 20 patients with anterior

cruciate ligament (ACL) injuries weretreated by quadrupled hamstring tendongraft (QHTG)—with or without PRP gelgrowth factor (GF) application. CT high-lighted a significant difference (P<0.01)between ACL density of the two groups.CT densities of the ACL and posteriorcruciate ligament (PCL) were similar inthe GF-treated group. In the controlgroup, however, the intensity of the sig-nal was heterogeneous and the new ACLwas not clearly identifiable with respect tothe PCL. A different density of the ACLwas also noted: in the GF-treated groupthis density was uniform and the new ACLwas more structured, while in the controlgroup the ligament was less structuredand did not completely fill the femoraland tibial tunnels. In the PRP treatedgroup, one patient had a synovitic reac-tion. On CT, the new ACL was increasedand hypertrophic and surrounded by asoft-tissue reaction. MRI confirmed thisfinding.32

Sanchez reported on a case-controlstudy of twelve athletes with completeachilles rupture. All twelve had openachilles repair; six had PRGF. The treat-ment group had no wound complicationsand experienced earlier functionalrestoration: ROM (7 vs. 11 wks), jogging(11 vs. 18 wks), and training (14 vs. 21

wks). The authors of this study measuredIGF-1, TGF-B1, PDGF-AB, EDF, VEGF,and HGF and noted that the number ofplatelets held direct correlation to thelevel of growth factors.33

Case Example: Chronic Tendonopathy A 63-year-old male ironman distancetriathlete presented with a history of leftachilles pain longer than three months.The patient had no relief with physicaltherapy or ultrasound (U/S) therapy fora six week duration. The patient was di-agnosed by MRI with stress fracture of thefibula with no discrete cortical line orfracture in addition to an achilles ten-donopathy. Diagnostic U/S in our officeshowed an 8cm segment of tendon colla-gen change consistent with a tendonopa-thy with associated peritenon fibrosis (seeFigure 4).

FIGURE 4. Diagnostic ultrasound of the leftachilles (proximal and distal) showing a largehypoechoic noninsertional tendonosis with sur-rounding fibrosis.

FIGURE 5.Diagnostic ultrasound of the left Achillestaken 1.5 months after initial PRP matrix graft-ing showing improved collagen organization, less-ened fibrosis, and improved capillary blood flow.

FIGURE 6. U/S pictures (3) proximal and dis-tal chronic tendonopathy with scarring andfibrosis of the VMO at the myotendinousjunction and insertion.

7

The patient undergoes three separateseries of PRP at four-week intervals to theachilles tendon and fibula along with theperoneal tendon sheath at the myotendi-nous junction. Subsequent ultrasoundsshow improved fibrosis and less scarringalong with collagen pattern reorganiza-tion consistent with improved vascularityand tendon structure (see Figure 5).

The patient has greater than 90% painreduction after the three PRP matrixgrafts and returns to ironman distanceracing after the three months of restrict-ed training. Supportive compressionsleeves are utilized for three months toallow for load distribution until strengthin the peroneal muscles and achilles is90% of the unaffected right side.

Muscle Strain and the Use of PRPSanchez reported a 20 patient prospec-tive muscle injury pilot study with six-month follow-up. Ultrasound guided in-jection of PRP within the injured muscleenhanced healing (echo-graphic images)and functional capacities 50% faster thanthe control group.34

Case Example: Quadriceps VMO MuscleStrainA 56-year-old male presented with rightthigh pain occurring for approximatelyone year. The pain is worse on the bike

and, in fact, is more prevalent when seat-ed and pushing large gears or uphillclimbing. The patient has no significantpain with running. The patient is an iron-man distance triathlete and remembersno injury of significance one year ago atonset. Ultrasound shows a vastus medialisinjury/strain pattern with associated fibertearing and fibrosis. This is near the VMOmyotendinous junction at the right knee(see Figure 6). No evidence of kneepathology is noted on physical exam oron ultrasound. Palpable tenderness existsat the strain site on the medial thigh. Painis also reproduced on eccentric loading ofthe VMO muscle group. No improvementhad been obtained previously with threeweeks of NSAID use, physical therapy, ormyofascial therapy work.

The patient undergoes a single injec-tion of PRP (4cc) along with 1cc of in-jectable collagen for matrix stabilizationat two discrete sites in the VMO musclewith ultrasound guidance (see Figure 7).

The patient’s pain after one month ismore than 80% resolved and the patienthas no pain on the bike or with activity aspreviously noted. Resumption of trainingoccurred one week following injection withswimming, running, and protected cycling.

Articular Cartilage and the Intra-ArticularUse of PRPEverts, Devilee, et al. reported that autol-ogous platelet gel and fibrin sealant en-hance the efficacy of total knee arthroplas-ty by improved range of motion, decreased

length of stay, and a reduced incidence ofarthrofibrosis. Everts’ team also investigat-ed whether the use of autologous derivedplatelet gel and fibrin sealant would reducepostoperative blood loss, decrease the im-paired range of motion, and reduce the in-cidence of arthrofibrosis. Study group pa-tients (n=85) were treated with the appli-cation of autologous platelet gel and fib-rin sealant at the end of surgery. Eighty pa-tients were operated without the use ofplatelet gel and fibrin sealant and servedas the control group. During a five-monthpostoperative period, patients were fol-lowed to observe the incidence of arthrofi-brosis. In patients in the treatment group,the hemoglobin concentration in blooddecreased significantly less when com-pared to the control group. They alsoshowed a superior postoperative range ofmotion when compared to those of thecontrol group (P<0.001). The incidence ofarthrofibrosis and subsequent forced ma-nipulation was significantly less (P<0.001)in patients managed with platelet gel andfibrin sealant.35

Case Example: Severe Hip OsteoarthritisWith a History of Congenital Hip DysplasiaA 56-year-old female presented with in-creasing left hip pain greater than oneyear duration. The patient has a history ofbilateral hip dislocations at birth (birthcountry Poland — no x-rays available) withevidence of shallow acetabular deformitynoted on x-ray (see Figure 8).

The patient is active in dance and is ofnormal weight and BMI. Some relief isobtained with NSAID therapy but pain isnow affecting sleep and is interfering withactivities of daily living and her dance reg-imen. The patient undergoes one PRP in-jection to the left hip using an anteriorapproach. 8cc PRP is placed with ultra-sound guidance as noted (see Figure 9).

FIGURE 7. U/S pictures (2) post injectionwith PRP and gel matrix at the myotendi-nous junction and the insertion.

FIGURE 8. X-ray of pelvis and affected left hippre-treatment with PRP matrix graft.

FIGURE 9. X-ray of left hip following PRP ma-trix graft series. X-ray shows subtle smoothingof the irregular femoral head surface.

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After 3 months, the patient reports 75%pain improvement and some improve-ment in ROM is also reported. The nightpain has resolved and the patient’s painis controlled with acetaminophen. She isable to resume dance and activities for fit-ness and health.

Bone and Periosteal Use Of PRPGandhi et al. observed normalized cellu-lar proliferation and chondrogenesis withan improved mechanical strength whenPRP was injected percutaneously in a dia-betic experimental femur fracture model.36

Sanchez et al. utilized PRP after reat-tachment of a large (2 cm) loose chondralbody in its crater in the medial femoralcondyle. Autologous plasma (PRP) was in-jected into the area between the craterand the fixed fragment. They state thatcomplete articular cartilage healing wasconsiderably accelerated, and the func-tional outcome was excellent, allowing arapid resumption of symptom-free athlet-ic activity.37

PRP has been used successfully in max-illofacial surgery in several studies includ-ing a randomized trial of 88 patients withmandibular defects treated with cancel-lous cellular marrow grafts with, or with-out, PRP. Grafts with PRP showed twicethe radiographic maturity at six monthsfollow up.2

Another case report describes a fifty-year old woman with nonunion ofhumerus who had undergone two unsuc-cessful operations. Union was obtainedby the use of autologous platelet-rich gel(PRG). At the 8th week, over 75% of thecircumference of the bone at the defectsite had resolved and, during later vis-its, remodeling of the union was ob-served on X-ray films and DEXA exam-inations. Maximum healing was reachedat the 18th week. Twelve months afterPRG injection, the intramedullary nailthat had previously been placed was re-moved.38

Case Example: Bilateral Pars Interarticu-laris Stress Fractures (Spondylolysis)A 14-year-old softball player presentedwith a history of developing back painover a period of six weeks, made worsefollowing a minor motor vehicle crashfour weeks prior to visit. The patient hadinitial pain and localized tenderness onthe right low back L4-5 area with a posi-tive stork test. X-ray and MRI confirmspondylolysis (see Figure 10).

The patient undergoes extensive phys-ical therapy for approximately 8 monthswith subsequent relief. The patient thenreturns to sport specific activity but rede-velops pain. After appropriate discussion

of the benefits and risks, a PRP matrixgraft is placed on the right L5-S1 facetjoint and the L5 pars with ultrasoundguidance. On return to activity, the pa-tient notes the absence of pain on theright pars or low back area. The patientis allowed to slowly return to activity. Twomonths following the initial PRP graft,the patient develops pain in the opposite,left lumbar area after repeated throwingdrills. A repeat MRI shows a left sidedspondylosis. No listhesis is appreciated.Evidence of healing is noted on the rightpars stress fracture to a small degree (seeFigure 11).

A PRP matrix graft—with a total 8ccPRP at a six-fold concentration andmixed with 2 cc 50:50 lidocaine 1% withmarcaine 0.5%—is then placed an addi-tional X3 on the right and X3 on the left,with approximately 5cc placed at the lev-

FIGURE 10. Initial MRI of the LS spine showsright sided pedicle stress reaction at vertebrallevel L5.

FIGURE 11. MRI repeat LS spine (approx. 1year following the initial MRI) with evidenceof new left pars defect at L5 with evident par-tial healing of right sided stress fracture.

FIGURE 12. Repeat MRI following four right-sided and three left-sided PRP matrix graftswith evident interval healing.

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els of the L5 pars as well as the accompa-nying facet joints. The patient is startedon physical therapy at two weeks into thegraft injection series with progression at6 weeks to pilates therapy and then sportspecific activity with heavy focus on themechanics of core stabilization and kinet-ic chain reintegration. A repeat MRI isobtained two months following PRP (seeFigure 12).

Figure 12 shows interval slight healingof the fracture sites. The patient has notdeveloped any reoccurrence of pain andis back to softball activities with no brac-ing. No tenderness remains at the priorfracture sites on physical exam.

In Vivo Studies: Skin Healing, Range ofMotion, and Pain With the Use of PRPA prospective, single-blind pilot studycomprising 80 full-thickness skin punchwounds (4mm diameter) was conductedon the thighs of eight healthy volunteers.With each subject serving as his or herown control (five punch sites per leg), PRPwas applied topically on one thigh, whilean antibiotic ointment and/or a semi-oc-clusive dressing was applied on the otherthigh. On day 17, the percentage of clo-sure was 81.1% for the PRP-treated sitesand 57.2% for the control sites. Also, thePRP wound closure velocities were signif-icantly faster than those of the controls(P=.001). When the platelet count in thegel was more than six times the baselineintravascular platelet count in some sub-jects, epithelialization and granulationformation appeared three days earlier inthe PRP-treated group.39

Everts et al. noted improved woundhealing when platelet leukocyte gel wasapplied during wound closure after totalknee arthroplasty.5

In a study examining PRP gel for dia-betic foot ulcers, Driver et al. noted that13 of 19 patients in the study group(68.4%) had complete healing, comparedwith only 9 of 21 (42.1%) of the controlgroup (saline gel). This study was aprospective, randomized, controlled trialwith both groups receiving a blood drawfor blinding purposes. The treatingproviders and patients were blinded tothe gel applied. It should be noted thatno treatment serious adverse events werereported and bovine thrombin used forPRP gel did not cause any Factor V inhi-bition.40

In another study from Everts et al.,platelet leukocyte gel (PLG) was injected

in the subacromial space during woundclosure in patients who underwent anopen subacromial decompression.41 Inthe PLG-treated patients, a decrease inthe VAS pain score was observed(P<0.001) compared to the non-treatedpatients. Consequently, the use of painmedication was significantly less(P<0.001) in PLG-treated patients. Fur-thermore, treated patients demonstrateda significantly improved range of motionearlier after surgery with a high shoulderfunctional index.

A significant reduction in pain was alsoobserved after PRP use by Fanning et al.after applications in gynecologic sur-gery42; Gardner and co-workers followingtotal knee replacement surgery43; andCrovetti and associates in patients withchronic wounds.44

ConclusionPRP matrix grafts along with other bio-logic grafting techniques are becomingmore prevalent in the treatment para-digms of musculoskeletal medicine.These PRP matrix grafts provide effec-tive, safe, relatively low-cost treatment op-tions to patients who have the time andwherewithal to allow collagen synthesisand maturation at the graft site. PRP ma-trix grafts appear to restore tissue home-ostasis and biotensegrity of collagen.Other pain inhibiting effects are also pres-ent in PRP matrix grafts which allow ear-lier resumption of pain free activity. It isthe authors’ experiences that these grafts,along with other regenerative graftingoptions, are at times the only viable treat-ment option for a select group of patientswith degenerative myofascial tissue in-juries. The authors recommend appropri-ate first line therapies such as relative rest,appropriate bracing and kinesiotaping,evaluation of kinetic chain mechanics,and physical therapy—with or without ec-centric loading protocols—prior to theutilization of these PRP matrix graftingprotocols.

Reduction in pain after PRP applica-tions has been observed by several au-thors. However, an explanation of thisphenomena has not always been given.The authors believe that serotonin re-leased from activated platelets might beresponsible for decreased pain, as de-scribed by Everts41 and Fanning.42 Exceptfor the growth factors in the Alpha-gran-ules, large amounts of serotonin45 are con-tained within the dense platelet granules.

Since platelet counts of the PRP are gen-erally almost six-fold higher when com-pared to whole blood levels, it stands toreason that serotonin levels are thereforealso significantly increased at the woundsite. This phenomena has been explainedin detail by Sprott et al.46 who reported onpain reduction following acupunctureand measured a decrease in serotoninconcentration in platelets from these pa-tients and an increase in serotonin levelsin plasma—suggesting normalization ofplasma serotonin levels due to the mobi-lization of platelet serotonin.

Other grafting tools such as the use ofautologous bone marrow aspirate stemcells (BMAC) with PRP matrices have notbeen explored in this article but may befound in further detail by the authors.These stem cell/growth factor grafts arebeing utilized for severe degenerativestates with associated tissue hypoxemia.Hence, PRP and other regenerative bio-cellur therapeutic matrices deserve fur-ther study to determine their effects in an-imal and human models. n

David M. Crane, MD practices Sports Med-icine in Chesterfield and Saint Louis, Mis-souri. He is Board Certified in EmergencyMedicine and Sports Medicine. Dr. Crane isthe founder and Director of the Crane ClinicSports Medicine. Dr. Crane utilizes the mostup to date therapies to assist the healing processin his patients, including Regenerative Injec-tion Therapy (RIT) which uses the patient'sown growth factors, or bioactive proteins, to en-courage the in-growth of normal collagen andremodeling of injured tissue. He may be con-tacted at: Crane Clinic Sports Medicine, 219Chesterfield Towne Centre, Chesterfield, MO63005, or by email through his website atwww.craneclinic.com.

Peter A.M. Everts, PhD heads the Depart-ment of Peri-Operative Blood Management atCatharina Hospital at Eindhoven, TheNetherlands. He is currently the chairman ofFoundation FERET which is the researchleader in the PRP medical field. Dr. Everts hasdone pioneering work involving autologousplatelet rich plasma in both animal and humantrials and wrote the 2007 thesis titled: Autol-ogous Platelet-Leukocyte-Enriched Gel:Basics and Efficacy, which describes a novelmethod to support soft tissue and bone healing(ISBN 10:90-8590-016-6, ISBN 13:978-90-8590-016-0). Dr. Everts may be contacted viaemail at everts@elive.nl.

References1. Ferrari M, Zia S, Valbonesi M, et al. A new tech-nique for hemodilution, preparation of autologousplatelet-rich plasma and intraoperative blood salvagein cardiac surgery. Int J Artif Org. 1987. 10: 47–50.2. Gamradt, Seth C, et al. Platelet Rich Plasma in Ro-tator Cuff Repair. Techniques in Orthopaedics. 22(1):26–33. 3. Everts PAM, Knape JTA, Weibrich G, SchönbergerJPAM, Hoffmann JJHL, Overdevest EP, Box HAM,and van Zundert A. Platelet-Rich Plasma and PlateletGel: A Review. JECT. 2006. 38: 174–187.4. Rivera J and Stephenson F. Personal communica-tion with author. 03/06. 5. Everts PA, Jakimowicz JJ, van Beek M, Schön-berger JP, Devilee RJ, Overdevest EP, Knape JT, andvan Zundert A. Reviewing the Structural Features ofAutologous Platelet-Leukocyte Gel and Suggestionsfor Use in Surgery. Eur Surg Res. 2007. 39: 199–207.6. Ibelgaufts, Horst. COPE: Cytokines & Cells OnlinePathfinder Encyclopaedia Version 19.4 (April 2007).http://www.copewithcytokines.de/. Last accessed12/09/07.7. Kevy SV and Jacobson MS. Comparison of meth-ods for point of care preparation of autologousplatelet gel. J Extra Corpor Technol. 2004. 36: 28–35.8. Marx RE. Platelet-rich plasma (PRP): what is PRPand what is not PRP? Implant Dent. 2001. 10:225–228.9. Kumar V et al. Chapter 2 - Acute and chronic in-flammation. In Robbins and Cotran Pathologic Basisof Disease, 7th ed. 2005. Saunders. Available atwww.mdconsult.com.10. Hesham El-Sharkawy et al. Platelet-Rich Plasma:Growth Factors and Pro- and Anti-Inflammatory Prop-erties. J Periodontol. April 2007. 78: 661-669.11. Haynesworth S et al. Mitogenic Stimulation ofHuman Mesenchymal Stem Cells by Platelet Releas-ate. Poster Presentation, American Academy of Or-thopedic Surgery. March 2001. 12. The Healing Effects of Autologous Platelet Gel onAcute Human Skin Wounds. Arch Facial Plast Surg.May-Jun 2007. 9(3): 174-183.13. Weibrich G, Hansen T, Kleis W, Buch R, and Hit-zler WE. Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone.2004. 34: 665–671.14. Liu YBA et al. Fibroblast Proliferatiion due to Ex-posure to a Platelet Concentrate in Vitro is pH De-pendent. Wound Rep Reg. 2002. 10: 336-340. 15. de la Torre J. The physicology of healing thechronic wound. http://www.emedicine.com/plastic/topic477.htm#section~the_physiology_of_healing_of_the_chronic_wound. Last Updated: May 26, 2006.Last accessed 12/09/07.16. Barnett Jr MD and Pomeroy GC. Use of Platelet-Rich Plasma and Bone Marrow Derived Mesenchy-

mal Stem Cells in Foot and Ankle Surgery. Tech-niques in Foot and Ankle Surgery. 2007. 6(2): 89–94. 17. www.Harvesttech.com. Last accessed 12/09/07.18. Virchenko O and Aspenberg P. How can oneplatelet injection after tendon injury lead to a strongertendon after 4 weeks? Interplay between early regen-eration and mechanical stimulation. Acta Orthopaedi-ca. 2006. 77 (5): 806–812.19. Ingber DE. The Architecture of Life: A universalset of building rules seems to guide the design of or-ganic structures—from simple carbon compounds tocomplex cells and tissues. Scientific American. Janu-ary 1998. pp 48-57.20. Ingber DE. Cellular tensegrity: defining new rulesof biological design that govern the cytoskeleton.Journal of Cell Science 104. 1993. pp 613-627.21. Creaney L and Hamilton B. Growth Factor Deliv-ery Methods in the Management of Sports Injuries:The State of Play. Br J Sports Med. 2007 10.1136: 1-16. Published online: Nov 5 2007. 22. Bielecki TM et al. Antibacterial effect of autolo-gous platelet gel enriched with growth factors andother active substances; an in vitro study. The Jour-nal of Bone and Joint Surgery. March 2007. 89-B(3):417-420.23. Scott JD and Pawson T. Cell communication: Theinside story. Sci Am. Jun 2000. pp 54-61.24. Personal communication of primary author andthe Center for Blood Research, Cambridge, MA. Feb-ruary 2007.25. Eduardo A et al. Autologous preparations rich ingrowth factors promote proliferation and induceVEGF and HGF production by human tendon cells inculture. J of Orthopaedic Research. 2005 23:281–286.26. Mishra A et al. Human Skin Fibroblast Proliferationin Buffered Platelet Rich Plasma. American Academyof Orthopaedic Surgeons Poster Presentation. March2006.27. Schnabel L et al. Platelet Rich Plasma (PRP) En-hances Anabolic Gene Expression Patterns in FlexorDigitorum Superficialis Tendons. J of Orthopaedic Re-search. 2006. pp 230-240.28. du Toit DF et al. Soft and Hard-tissue Augmenta-tion with Platelet-rich Plasma: Tissue Culture Dynam-ics, Regeneration and Molecular Biology Perspective.Int J Shoulder Surg. April 2007. 1(2): 64-73.29. Mishra A et al. Treatment of Chronic Elbow Tendi-nosis with Buffered Platelet-Rich Plasma. AmericanJournal of Sports Medicine. 2006. 34: 1774-1778.30. Barett S. Growth Factors for Chronic PlantarFasciitis? Podiatry Today. 2004. 17: 36-42.31. Scarpone MA, Davenport M, and Rauker N. PRPas a Treatment Alternative for Symptomatic RotatorCuff Tendinopathy for Patients Failing ConservativeTreatment. 2005. http://www.treatingpain.com/pages/int_pain/ScarponeRotatorCuffstudy.pdf. Last ac-cessed 1/2/08.

32. Ventura A et al. Use of Growth Factors in ACLSurgery: Preliminary Study. Journal of OrthopaedicTraumatology. 2005. 6: 76-79.33. Sanchez M, Anitua E, Azofra J et al. Comparisonof surgically repaired Achilles tendon tears usingplatelet-rich fibrin matrices. Am J Sp Med. 2007.35(2): 245-251.34. Sanchez M, et al. Application of AutologousGrowth Factors on Skeletal Muscle Healing. 2ndWorld Congress on Regenerative Medicine. PodiumPresentation. May, 2005.35. Everts PAM, Devilee R et al. Autologous plateletgel and fibrin sealant enhance the efficacy of totalknee arthroplasty: improved range of motion, de-creased length of stay and a reduced incidence ofarthrofibrosis. Knee Surg Sports Traumatol Arthrosc.January 2007. 36. Gandhi A, Dumas C, O’Conner JP, Parsons JR,and Lin SS. The effects of local platelet delivery ondiabetic fracture healing. Bone. 2006. 38: 540–546.37. Sanchez M et al. Plasma Rich in Growth Factorsto Treat Articular Cartilage Avulsion: A Case Report.Medicine & Science in Sports & Exercise. 2003. pp1648-1652.38. Bielecki TM. Percutaneous Injection Of Autoge-nous Growth Factors In Patient With Nonunion OfThe Humerus. A Case Report. J Orthopaedics. 2006.3(3): e15.39. The Healing Effects of Autologous Platelet Gel onAcute Human Skin Wounds. Arch Facial Plast Surg.May-Jun 2007. 9(3): 174-183.40. Driver V et al. A Prospective, Randomized, Con-trolled Trial of Autologous Platelet-Rich Plasma Gelfor the Treatment of Diabetic Foot Ulcers. Ostomy/Wound Management. 2006. 52(6): 68 - 87.41. Everts PAM, Devilee RJJ, Brown Mahoney C, etal. Exogenous application of platelet-leukocyte gelduring open subacromial decompression contributesto improved patient outcome. A prospective random-ized double-blinded study. Eur Surg Res. 2008. 40:203–210. 42. Fanning J, Murrain L, Flora R, Hutchings, John-son J, and Fenton B. Phase I/II prospective trial ofautologous platelet tissue graft in gynaecologicsurgeru. J Min Invas Gyn. 2007. 14: 633-637. 43. Gardner MJ, Demetrakopoulos D, Klepchick PR,and Mooar PA. The efficacy of autologous plateletgel in pain control and blood loss in total kneearthroplasty. Int Orthop. 2006. 31: 309-313. 44. Crovetti G, Martinelli G, Issi M, et al. Platelet gelfor healing cutaneous chronic wounds. Transfusionand Apheresis Science. 2004. 30: 145-151 45. Vanhoutte PM. Platelet-derived serotonin, the en-dothelium, and cardiovascular disease. J CardiovascPharmacol. 1991. 17S: S6–S12. 46. Sprott H, Franke S, Kluge H, and Hein G. Paintreatment of fibromyalgia by acupuncture. RheumatolInt. 1998. 18: 35–36.

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