**10. Platelet Rich Plasma (PRP)**

Platelet-rich plasma (PRP) is derived from centrifuging whole blood andhas a platelet concentration higher than that of whole blood. It is the cellular component of plasma that settles after centrifugation, which contains various growth factors (GFs). Unfortunately, despite its increasing popularity as a treatment for soft tissue injuries, there remains neither a uniform terminology nor an understanding as to what constitutes PRP. Terminology in common usage includes platelet enriched plasma (PEP) and plasma (preparation) rich in GFs (PRGFs); however, many of these terms are associated with commercial products [34].

Based on a limited number of animal model studies that have shown a positive impact of isolated recombinant GF on muscle regeneration, the application of PRP to an injured muscle is thought to accelerate regeneration, enhance healing and decrease the risk of re-injury. Studies using animal models show a reduction in the recovery time, in particular on the early stages of reparation. Early clinical trials, though mainly consisting of level 3 and level 4 evidence, show an improvement of healing for muscle injury in terms of earlier return to play [35,36].

The use of PRP as a source of GF seems attractive because it is easily obtainable with a simple apparatus and is relatively affordable. Moreover, its use has rapidly gained the support of the popular media as a result of its purported ''natural'' properties, high level of efficacy, and lack of side effects.

It has been shown that anti-fibrotic agents (suramin which acts as a TGF-β1 inhibitor by competitively binding to the growth factor's receptor) inhibits fibroblast proliferation and neutralizes the stimulating effect of TGF-β1 on the proliferation of fibroblasts in vitro (ref). An in-vivo injection of suramin (5.0 mg) two weeks after strain injury reduced muscle fibrosis and enhanced muscle regeneration, thereby leading to improved muscle strength recovery (ref). The clinical use of suramin has already been approved by the Food and Drug Administration. Although suramin can lead to side effects when administered intravenously, local intramus‐ cular injection may not elicit the same deleterious effects and could be very useful in improving muscle healing. However, further studies are necessary in order to assess the safety and the

Theoreticallys, the restitution of blood supply to the injured area is fundamental for the regeneration process, in particular for the myotubes which depend soley on aerobic metabo‐ lism as the source of energy required for their regeneration. This is the basis for the application of Hyperbaric Oxygen Therapy in muscle lesions. Clinical trials are lacking, however a recent experimental study showed positive effects of this treatment on muscle injury. Further research should assess the clinical outcome of Hyperbaric Oxygen Therapy before it may be

Platelet-rich plasma (PRP) is derived from centrifuging whole blood andhas a platelet concentration higher than that of whole blood. It is the cellular component of plasma that settles after centrifugation, which contains various growth factors (GFs). Unfortunately, despite its increasing popularity as a treatment for soft tissue injuries, there remains neither a uniform terminology nor an understanding as to what constitutes PRP. Terminology in common usage includes platelet enriched plasma (PEP) and plasma (preparation) rich in GFs (PRGFs);

Based on a limited number of animal model studies that have shown a positive impact of isolated recombinant GF on muscle regeneration, the application of PRP to an injured muscle is thought to accelerate regeneration, enhance healing and decrease the risk of re-injury. Studies using animal models show a reduction in the recovery time, in particular on the early stages of reparation. Early clinical trials, though mainly consisting of level 3 and level 4 evidence, show an improvement of healing for muscle injury in terms of earlier return to play

The use of PRP as a source of GF seems attractive because it is easily obtainable with a simple apparatus and is relatively affordable. Moreover, its use has rapidly gained the support of the

however, many of these terms are associated with commercial products [34].

effectiveness of this treatment [32].

162 Muscle Injuries in Sport Medicine

**9. Hyperbaric oxygen therapy**

suggested for this kind of pathology [33].

**10. Platelet Rich Plasma (PRP)**

[35,36].

Limited risk of infection is linked to any injective technique but risk may be limited by the use of a correct sterile procedure, Moreover, the utilization of autologus blood guarantees the elimination of the risk of allergic reactions and the possibility to become in contact with infected blood. Previously, bovine derived drugs sometimes led to potentially lethal pathologies of coagulation and they have since been withdrawn from the market.

It seems that PRP does not have a systemic effect, but there is minimal research demonstrating this fact.. Nowadays, there is no evidence that PRP has a carcinogenetic effect. This is also supported by the mechanism of action as growth factors do not penetrate the cellular mem‐ brane; therefore they cannot generate DNA mutations. Actually, no other carcinogenetic mechanisms are known, so in general, PRP technique seems to be safe in this respect.

The risk of local complications linked to the use of the PRP technique seems to be more disputed. However, local tissue degeneration, muscular architecture alteration, increasing recurrence rate are all complications which have been taken into consideration in both basic and clinical research. Currently, no studies support such complications.

Different considerations regarding the risk of fibrosis are also of concern. TGF-β1 is the main regulating factor of fibrosis. Thus, it can be speculated that an incorrect use of growth factors may lead to an increase of fibrosis and a potential negative outcome in term of return to play.

From an anti-doping perspective, the topical use of growth factors has been approved. This was probably due to the demonstrable absence of any systemic effect of growth factors.

However, despite its elevated public profile and theoretical benefits, there remains many unanswered questions surrounding the use of these techniques in the management of muscle injuries, and the burden of proof remains with scientists and practitioners to confirm or refute the clinical utility of this technology.

One of the main issues seems to be determining the appropriate PRP concentration to use. Different products are present on the Orthopedics and Sport Medicine market.. However, each product presents different protocols and methods to concentrate the platelets resulting in products with different biological properties. Even if most of the products yield 10% (that means 2ml of PRP for every 20ml of blood withdrawn), their concentration of growth factors is different. It has been estimated that the growth factor concentration may vary from 3 to 27 times blood concentration. Considering that a low concentration of PRP may not give satis‐ factory clinical results and an excessively elevated concentration may start inhibitory proc‐ esses, it appears fundamental that the concentration should be carefully monitored and controlled. Some authors indicate that the ideal concentration of PRP is four to six times the normal platelet blood concentration.

Another source of discussion is related to the presence (or absence) of White Blood Cells (WBC) in PRP. It is unclear whether the presence of white cells in PRP is an advantage or an obstacle to healing. In fact, if the anti-infective potentialities of WBC may be of benefit, their proin‐ flammatory nature may actually be counterproductive to healing. This premise is consistent with the current understanding of the potential negative effects of inflammatory mediators on muscle healing.

**12. Conclusion**

any therapeutic intervention.

Aspetar Hospital, Doha, Qatar

Cristiano Eirale and Giannicola Bisciotti

Pathol Microbiol Scand. 83A: 259-265, 1975b.

Acta Pathol Microbiol Scand.1976;84A:85-94.

**Author details**

**References**

Medical treatments of muscle injuries have limited scientific evidence. Their use is often based on level four studies and on personal clinical experience. While /immobilization/mobilization and RICE seem to be established protocols and "classic" treatment (NSAIDs, painkillers) appears to have a limited impact, the effectiveness of any new options for treatment has yet to be demonstrated in sport medicine. While further research is warranted, the sharing of clinical experience amongst sport medicine practitioners seems fundamental in order to perform the best "clinically-based" choices. Our personal experience is that patient reactions to medical treatments are often unpredictable. The same treatment applied to the same kind of lesion in different subjects may have a completely different outcome. However, in our personal clinical experience, oftenthe same patient reacts well to the same treatment when proven successful with a previous injury. The placebo effect component of treatment is undeniable, however there could also be benefits which are highlighted more in some patients and less in others. Our conclusion is that different techniques must be considered when approaching management of a muscle lesion, due to the fact that no one technique has a strong scientific evidence base to its effectiveness. The physician should try to tailor the therapeutic choice on the bases of the lesion's characteristics, the patient needs and expectations, and the subjective reaction to different treatments in the past. Of course, the basic Hippocratic principle of the treatment safety ("Primum, non nocere"), should be always respected, in particular when approaching these kind of lesions which have been proven to heal very well without

Medical Treatment of Muscle Lesion http://dx.doi.org/10.5772/56329 165

[1] Järvinen M., Sorvari T. Healing of a crush injury in rat striated muscle, 1: description and testing of a new method of inducing a standard injury to the calf muscles. Acta

[2] Järvinen M. Healing of a crush injury in rat striated muscle: a microangiographical study of the effect of early mobilization and immobilization on capillary ingrowth.

[3] Järvinen TAH., Järvinen TLN., Kääriänen M., Kalimo H., Järvinen M. Muscle injury.

Biology and treatment. Am. J Sports Med. 33(5): 745-764, 2005.

Currently, it remains unclear what the impact PRP, with or without the presence of WBC, may have on the inflammatory cascade following muscle injury [37] In addition, each muscle has distinct anatomical and physiological characteristics, and as demonstrated in rabbit studies, also has distinct GF response profiles to injury. Thus, each location of injury may theoretically require different PRP preparations.

Another dilemma is the method of PRP subministration. The physiological impact on an acute muscle injury of a bolus infiltration of an unknown concentration of platelets, and thus of GF, and other factors that are found in any PRP preparation is still a mystery. Animal studies suggest that a bolus dose of recombinant GF is not as effective as sustained release. However, with the current utilized technique, all GFs are released within 1 hour from their application and this may potentially reduce their effectiveness.

The timing of application is also a source of discussion. Apparently, the first ten days (inflam‐ matory and regenerative phases) after the lesion may constitute the ideal moment for PRP injection. An application two to three weeks after an injury, with an environment preferentially upregulated by platelet TGF-b a, may actually favor fibrosis over regeneration.

Finally, although the physiological milieu should be sufficient to activate platelets, it is unknown if a preinfiltration activation is necessary [38].

In conclusion, the use of PRP is actually based on anecdotal reports and expert opinion (Level IV evidence). Further research is necessary in order to confirm or deny the effectiveness of PRP in muscle strain. However, the apparent safety and facility of application suggests that sport medicine practitioners should consider PRP when treating elite athletes, for whom such innovative approaches may be fundamental in terms of success.
