Platelet-Rich Plasma Versus Polydeoxyribonucleotide for Myofascial Pain Syndrome and Musculoskeletal Disorders: A Narrative Review of Mechanisms, Clinical Evidence, and Translational Considerations.

Myofascial pain syndrome (MPS) of the cervicoscapular girdle-most typically involving the upper trapezius and the rhomboid muscles-is among the most frequent causes of chronic regional musculoskeletal pain, yet the mainstays of interventional treatment (dry needling, local anesthetic trigger point injection, corticosteroid, botulinum toxin) act principally on nociceptive transmission or on the contractile taut band rather than on the disordered tissue biology that sustains it. Two injectable biologics with fundamentally different design logic have been proposed to fill this gap. Platelet-rich plasma (PRP) is an autologous, polypharmacological concentrate that delivers a supraphysiological bolus of platelet α-granule growth factors and leukocyte-dependent immunomodulators. Polydeoxyribonucleotide (PDRN) is a standardized, allogeneic-source (salmonid sperm DNA) low-molecular-weight deoxyribonucleotide mixture that acts through a single defined molecular target, the adenosine A2A receptor, supplemented by nucleoside salvage. This narrative review contrasts the two agents across four axes: (i) molecular and cellular mechanism; (ii) the biological plausibility of each in the specific microenvironment of the myofascial trigger point (MTrP)-an acidic, hypoxic, sensitizer-rich focus; (iii) the current clinical evidence in MPS and, by extension, across tendinopathy, plantar fasciitis, knee osteoarthritis, and acute muscle injury; and (iv) practical translational considerations including standardization, regulatory status, cost, and trial design. We conclude that PRP has the broader and methodologically stronger clinical evidence base in tendon and joint indications but is undermined by preparation heterogeneity and by consistently negative results in acute muscle injury, whereas PDRN offers reproducibility, an anti-inflammatory and pro-angiogenic profile that maps plausibly, based on preclinical evidence, onto MTrP pathophysiology, though direct validation in human myofascial tissue is lacking, and an excellent safety record, but is supported almost entirely by small, short-horizon, and frequently non-randomized studies. Neither agent can currently be recommended as standard care for trapezius or rhomboid MPS. We propose a mechanistic rationale and a concrete trial framework, including muscle-specific ultrasound-guided delivery, pressure pain threshold and Neck Disability Index as co-primary endpoints, and mandatory injectate characterization, for the head-to-head studies that the field now requires.