Review Article| Volume 34, ISSUE 1, P165-180, February 2023


A Narrative Review of Mechanisms, Techniques, and Protocols, and Evidence for Common Musculoskeletal Conditions
Published:October 17, 2022DOI:


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        • Hauser R.A.
        • Lackner J.B.
        • Steilen-Matias D.
        • et al.
        A systematic review of dextrose prolotherapy for chronic musculoskeletal pain.
        Clin Med Insights Arthritis Musculoskelet Disord. 2016; 9 (CMAMD-S39160): 139-159
        • American Academy of Orthopaedic Surgeons
        The burden of musculoskeletal diseases in the united states: prevalence, societal, and economic cost.
        Am Acad Orthopaedic Surgeons. 2009; 208
        • Goswami A.
        J Pain Palliat Care Pharmacother. 2012; 26: 376-378
        • DeChellis D.M.
        • Cortazzo M.H.
        Regenerative medicine in the field of pain medicine: Prolotherapy, platelet-rich plasma therapy, and stem cell therapy—Theory and evidence. Techniques in Regional Anesthesia and Pain.
        Management. 2011; 15: 74-80
        • Rabago D.
        • Slattengren A.
        • Zgierska A.
        Prolotherapy IN PRIMARY CARE PRACTICE.
        Prim Care Clin Office Pract. 2010; 37: 65-80
        • Hackett G.S.
        • Hemwall G.A.
        • Montgomery G.A.
        Ligament and tendon relaxation.
        Charles C Thomas, 1958
        • Borg-Stein J.
        • Osoria H.L.
        • Hayano T.
        Regenerative sports medicine: past, present, and future (adapted from the PASSOR Legacy Award Presentation; AAPMR; October 2016).
        PM&R. 2018; 10: 1083-1105
        • Thorens B.
        • Mueckler M.
        Glucose transporters in the 21st Century.
        Am J Physiology-Endocrinology Metab. 2010; 298: E141-E145
        • Reeves K.D.
        Prolotherapy: basic science, clinical studies, and technique. Pain Procedures in Clinical Practice.
        2nd Ed. Hanley and Belfus Philadelphia, 2000: 172-190
        • Yoshii Y.
        • Zhao C.
        • Schmelzer J.D.
        • et al.
        The effects of hypertonic dextrose injection on connective tissue and nerve conduction through the rabbit carpal tunnel.
        Arch Phys Med Rehabil. 2009; 90: 333-339
        • Ekwueme E.C.
        • Mohiuddin M.
        • Yarborough J.A.
        • et al.
        Prolotherapy induces an inflammatory response in human tenocytes in vitro.
        Clin Orthopaedics Relat Research®. 2017; 475: 2117-2127
        • Mobasheri A.
        Glucose: an energy currency and structural precursor in articular cartilage and bone with emerging roles as an extracellular signaling molecule and metabolic regulator.
        Front Endocrinol. 2012; 3: 153
        • Stecker M.M.
        • Stevenson M.
        Effect of glucose concentration on peripheral nerve and its response to anoxia.
        Muscle & nerve. 2014; 49: 370-377
        • Topol G.A.
        • Podesta L.A.
        • Reeves K.D.
        • et al.
        Chondrogenic effect of intra-articular hypertonic-dextrose (prolotherapy) in severe knee osteoarthritis.
        PM&R. 2016; 8: 1072-1082
        • Dommerholt J.
        Dry needling—peripheral and central considerations.
        J Man Manipulative Ther. 2011; 19: 223-227
        • Han D.S.
        • Lee C.H.
        • Shieh Y.D.
        • et al.
        A role for substance P and acid-sensing ion channel 1a in prolotherapy with dextrose-mediated analgesia in a mouse model of chronic muscle pain.
        Pain. 2021; 163: 622-633
        • Kietrys D.M.
        • Palombaro K.M.
        • Azzaretto E.
        • et al.
        Effectiveness of dry needling for upper-quarter myofascial pain: a systematic review and meta-analysis.
        J Orthop Sports Phys Ther. 2013; 43: 620-634
        • Kim H.J.
        • Jeong T.S.
        • Kim W.S.
        • et al.
        Comparison of histological changes in accordance with the level of dextrose-concentration in experimental prolotherapy model.
        J Korean Acad Rehabil Med. 2003; 27: 935-940
        • Nair L.S.
        Prolotherapy for tissue repair.
        Translational Res. 2011; 158: 129-131
        • Finnoff J.T.
        • Hall M.M.
        • Adams E.
        • et al.
        American Medical Society for Sports Medicine (AMSSM) position statement: interventional musculoskeletal ultrasound in sports medicine.
        PM&R. 2015; 7: 151-168
        • Fullerton B.D.
        • Reeves K.D.
        Ultrasonography in regenerative injection (prolotherapy) using dextrose, platelet-rich plasma, and other injectants.
        Phys Med Rehabil Clin. 2010; 21: 585-605
        • Bellapianta J.
        • Swartz F.
        • Lisella J.
        • et al.
        Randomized prospective evaluation of injection techniques for the treatment of lateral epicondylitis.
        Orthopedics. 2011; 34: e708-e712
        • Dagenais S.
        • Ogunseitan O.
        • Haldeman S.
        • et al.
        Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: a survey of practitioners.
        Arch Phys Med Rehabil. 2006; 87: 909-913
        • Distel L.M.
        • Best T.M.
        Prolotherapy: a clinical review of its role in treating chronic musculoskeletal pain.
        PM R. 2011; 3
        • Rabago D.
        • Lee K.S.
        • Ryan M.
        • et al.
        Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): Results of a single-blind, pilot-level, randomized controlled trial.
        Am J Phys Med Rehabil. 2013; 92: 587-596
        • Scarpone M.
        • Rabago D.P.
        • Zgierska A.
        • et al.
        The efficacy of prolotherapy for lateral epicondylosis: a pilot study.
        Clin J Sport Med. 2008; 18: 248-254
        • Shin J.Y.
        • Seo K.M.
        • Kim D.K.
        • et al.
        The effect of prolotherapy on lateral epicondylitis of elbow.
        J Korean Acad Rehabil Med. 2002; 26: 764-768
        • Park J.H.
        • Song I.S.
        • Lee J.B.
        • et al.
        Ultrasonographic findings of healing of torn tendon in the patients with lateral epicondylitis after prolotherapy.
        J Korean Soc Med Ultrasound. 2003; 22: 177-183
        • Yelland M.
        • Rabago D.
        • Ryan M.
        • et al.
        Prolotherapy injections and physiotherapy used singly and in combination for lateral epicondylalgia: a single-blinded randomised clinical trial.
        BMC Musculoskelet Disord. 2019; 20: 509
        • Akcay S.
        • Gurel Kandemir N.
        • Kaya T.
        • et al.
        Dextrose prolotherapy versus normal saline injection for the treatment of lateral epicondylopathy: a randomized controlled trial.
        J Altern Complement Med. 2020; 26: 1159-1168
        • Carayannopoulos A.
        • Borg-Stein J.
        • Sokolof J.
        • et al.
        Prolotherapy versus corticosteroid injections for the treatment of lateral epicondylosis: a randomized controlled trial.
        PM R. 2011; 3: 706-715
        • Apaydin H.
        • Bazancir Z.
        • Altay Z.
        Injection therapy in patients with lateral epicondylalgia: hyaluronic acid or dextrose prolotherapy? a single-blind, randomized clinical trial.
        J Altern Complement Med. 2020; 26: 1169-1175
        • Seven M.M.
        • Ersen O.
        • Akpancar S.
        • et al.
        Effectiveness of prolotherapy in the treatment of chronic rotator cuff lesions.
        Orthopaedics Traumatol Surg Res. 2017; 103: 427-433
        • Bertrand H.
        • Reeves K.D.
        • Bennett C.J.
        • et al.
        Dextrose prolotherapy versus control injections in painful rotator cuff tendinopathy.
        Arch Phys Med Rehabil. 2016; 97 (W.B. Saunders): 17-25
        • Ryu K.
        • Ko D.
        • Lim G.
        • et al.
        Ultrasound-guided prolotherapy with polydeoxyribonucleotide for painful rotator cuff tendinopathy.
        Pain Res Manag. 2018; 2018: 8286190
        • Catapano M.
        • Zhang K.
        • Mittal N.
        • et al.
        Effectiveness of dextrose prolotherapy for rotator cuff tendinopathy: a systematic review.
        PM&R. 2020; 12: 288-300
        • Monteagudo M.
        • de Albornoz P.M.
        • Gutierrez B.
        • et al.
        Plantar fasciopathy: a current concepts review.
        EFORT Open Rev. 2018; 3: 485-493
        • Ersen Ö.
        • Koca K.
        • Akpancar S.
        • et al.
        A randomized-controlled trial of prolotherapy injections in the treatment of plantar fasciitis.
        Turkish J Phys Med Rehabil. 2017; 64: 59-65
        • Mansiz-Kaplan B.
        • Nacir B.
        • Pervane-Vural S.
        • et al.
        Effect of dextrose prolotherapy on pain intensity, disability, and plantar fascia thickness in unilateral plantar fasciitis: a randomized, controlled, double-blind study.
        Am J Phys Med Rehabil. 2020; 99: 318-324
        • Kesikburun S.
        • Uran Şan A.
        • Kesikburun B.
        • et al.
        Comparison of ultrasound-guided prolotherapy versus extracorporeal shock wave therapy in the treatment of chronic plantar fasciitis: a randomized clinical trial.
        J Foot Ankle Surg. 2021;
        • Asheghan M.
        • Hashemi S.E.
        • Hollisaz M.T.
        • et al.
        Dextrose prolotherapy versus radial extracorporeal shock wave therapy in the treatment of chronic plantar fasciitis: a randomized, controlled clinical trial.
        Foot Ankle Surg. 2021; 27: 643-649
        • Kim E.
        • Lee J.H.
        Autologous platelet-rich plasma versus dextrose prolotherapy for the treatment of chronic recalcitrant plantar fasciitis.
        PM R. 2014; 6: 152-158
        • Yelland M.J.
        • Sweeting K.R.
        • Lyftogt J.A.
        • et al.
        Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial.
        Br J Sports Med. 2011; 45: 421-428
        • Maxwell N.J.
        • Ryan M.B.
        • Taunton J.E.
        • et al.
        Sonographically guided intratendinous injection of hyperosmolar dextrose to treat chronic tendinosis of the Achilles tendon: a pilot study 2007;189:w215–20.
        AJR Am J Roentgenol. 2007; 189: 215-220
        • Ryan M.
        • Wong A.
        • Taunton J.
        Favorable outcomes after sonographically guided intratendinous injection of hyperosmolar dextrose for chronic insertional and midportion achilles tendinosis.
        AJR Am J Roentgenol. 2010; 194: 1047-1053
        • Reeves K.D.
        • Hassanein K.
        Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and Trapeziometacarpal) joints: evidence of clinical efficacy.
        J Altern Complement Med. 2000; 6: 311-320
        • Jahangiri A.
        • Moghaddam F.R.
        • Najafi S.
        Hypertonic dextrose versus corticosteroid local injection for the treatment of osteoarthritis in the first carpometacarpal joint: a double-blind randomized clinical trial.
        J Orthop Sci. 2014; 19: 737-743
        • Rabago D.
        • Patterson J.J.
        • Mundt M.
        • et al.
        Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial.
        Ann Fam Med. 2013; 11: 229-237
        • Reeves K.D.
        • Hassanein K.
        Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity.
        Altern Ther Health Med. 2000; 6 (77-80): 68-74
        • Eslamian F.
        • Amouzandeh B.
        Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up.
        Ther Adv Musculoskelet Dis. 2015; 7: 35-44
        • Reeves D.
        • Rabago D.
        Therapeutic injection of dextrose: Prolotherapy, perineural injection therapy and hydrodissection.
        PM&R Knowledge Now. 2019;
        • Pishgahi A.
        • Abolhasan R.
        • Shakouri S.K.
        • et al.
        Effect of dextrose prolotherapy, platelet rich plasma and autologous conditioned serum on knee osteoarthritis: a randomized clinical trial.
        Iranian J Allergy Asthma Immunol. 2020;
        • Rezasoltani Z.
        • Azizi S.
        • Najafi S.
        • et al.
        Physical therapy, intra-articular dextrose prolotherapy, botulinum neurotoxin, and hyaluronic acid for knee osteoarthritis: randomized clinical trial.
        Int J Rehabil Res. 2020; 43: 219-227
        • Arias-Vázquez P.I.
        • Tovilla-Zárate C.A.
        • Legorreta-Ramírez B.G.
        • et al.
        Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: systematic review of clinical trials.
        Adv Rheumatol. 2019; 59: 39
        • Yelland M.J.
        • Glasziou P.P.
        • Bogduk N.
        • et al.
        Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial.
        Spine. 2004; 29: 9-16
        • Dechow E.
        • Davies R.K.
        • Carr A.J.
        • et al.
        A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain.
        Rheumatology. 1999; 38: 1255-1259
        • Yelland M.
        • del Mar C.
        • Pirozzo S.
        • et al.
        Prolotherapy injections for chronic low-back pain.
        in: Yelland M. Cochrane database of systematic reviews. John Wiley & Sons, Ltd, 2004
        • Khan S.
        • Kumar A.
        • Varshney M.
        • et al.
        Dextrose prolotherapy for recalcitrant coccygodynia.
        J Orthop Surg. 2008; 16: 27-29
        • Miller M.R.
        • Mathews R.S.
        • Reeves K.D.
        Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose.
        Pain Physician. 2006; 9: 115-121
        • Cusi M.
        • Saunders J.
        • Hungerford B.
        • et al.
        The use of prolotherapy in the sacroiliac joint.
        Br J Sports Med. 2010; 44: 100-104
        • Hoffman M.D.
        • Agnish V.
        Functional outcome from sacroiliac joint prolotherapy in patients with sacroiliac joint instability.
        Complement Therapies Med. 2018; 37: 64-68
        • Zhou H.
        • Hu K.
        • Ding Y.
        Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation.
        Br J Oral Maxillofac Surg. 2014; 52: 63-66
        • Taşkesen F.
        • Cezairli B.
        Efficacy of prolotherapy and arthrocentesis in management of temporomandibular joint hypermobility.
        CRANIO. 2020; : 1-9
        • Priyadarshini S.
        • Gnanam A.
        • Sasikala B.
        • et al.
        Evaluation of prolotherapy in comparison with occlusal splints in treating internal derangement of the temporomandibular joint – A randomized controlled trial.
        J Cranio-Maxillofacial Surg. 2021; 49: 24-28
        • Reeves K.
        • Hassanein K.M.
        Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity.
        Altern Ther Health Med. 2003; 9: 58-62
        • Hauser R.A.
        • Matias D.
        • Woznica D.
        • et al.
        Lumbar instability as an etiology of low back pain and its treatment by prolotherapy: A review.
        J Back Musculoskeletal Rehabil. 2022; : 1-12