A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain

Ross A Hauser, Johanna B Lackner, Danielle Steilen-Matias, David K Harris, Ross A Hauser, Johanna B Lackner, Danielle Steilen-Matias, David K Harris

Abstract

Objective: The aim of this study was to systematically review dextrose (d-glucose) prolotherapy efficacy in the treatment of chronic musculoskeletal pain.

Data sources: Electronic databases PubMed, Healthline, OmniMedicalSearch, Medscape, and EMBASE were searched from 1990 to January 2016.

Study selection: Prospectively designed studies that used dextrose as the sole active prolotherapy constituent were selected.

Data extraction: Two independent reviewers rated studies for quality of evidence using the Physiotherapy Evidence Database assessment scale for randomized controlled trials (RCTs) and the Downs and Black evaluation tool for non-RCTs, for level of evidence using a modified Sackett scale, and for clinically relevant pain score difference using minimal clinically important change criteria. Study population, methods, and results data were extracted and tabulated.

Data synthesis: Fourteen RCTs, 1 case-control study, and 18 case series studies met the inclusion criteria and were evaluated. Pain conditions were clustered into tendinopathies, osteoarthritis (OA), spinal/pelvic, and myofascial pain. The RCTs were high-quality Level 1 evidence (Physiotherapy Evidence Database ≥8) and found dextrose injection superior to controls in Osgood-Schlatter disease, lateral epicondylitis of the elbow, traumatic rotator cuff injury, knee OA, finger OA, and myofascial pain; in biomechanical but not subjective measures in temporal mandibular joint; and comparable in a short-term RCT but superior in a long-term RCT in low back pain. Many observational studies were of high quality and reported consistent positive evidence in multiple studies of tendinopathies, knee OA, sacroiliac pain, and iliac crest pain that received RCT confirmation in separate studies. Eighteen studies combined patient self-rating (subjective) with psychometric, imaging, and/or biomechanical (objective) outcome measurement and found both positive subjective and objective outcomes in 16 studies and positive objective but not subjective outcomes in two studies. All 15 studies solely using subjective or psychometric measures reported positive findings.

Conclusion: Use of dextrose prolotherapy is supported for treatment of tendinopathies, knee and finger joint OA, and spinal/pelvic pain due to ligament dysfunction. Efficacy in acute pain, as first-line therapy, and in myofascial pain cannot be determined from the literature.

Keywords: dextrose; evidence-based medicine; musculoskeletal pain; osteoarthritis chronic pain; prolotherapy; systematic review.

Figures

Figure 1
Figure 1
Prevalence of musculoskeletal diseases in the United States. Note: National Center for Health Statistics, National Health Interview Survey, 2012.
Figure 2
Figure 2
The biology of prolotherapy. Prolotherapy induces the three stages of healing and restoration: inflammation, proliferation, and tissue remodeling. Reused from: Steilen D, Hauser R, Woldin B, Sawyer S. Chronic Neck Pain: Making the Connection Between Capsular Ligament Laxity and Cervical Instability. The Open Orthopaedics Journal. 2014;8:326–345, under the terms of a CC-BY 2.5 license.

References

    1. Institute of Medicine . Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): IOM; 2011.
    1. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics Health . With Chartbook on Trends in the Health of Americans. Hyattsville, MD: National Center for Health Statistics; 2006. (DHHS Publication No. 2006-1232).
    1. National Center for Health Statistics National Health Interview Survey. 2012. [Accessed June 21, 2014]. Available at: .
    1. Center for Disease Control and Prevention National Ambulatory Medical Care Survey. 2010. [Accessed August 14, 2014]. Available at .
    1. United States Bone and Joint Decade . The Burden of Musculoskeletal Diseases in the United States. First ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2008. p. 42.
    1. United States Bone and Joint Initiative . The Burden of Musculoskeletal Diseases in the United States. Second ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2011.
    1. National Research Council and the Institute of Medicine . Musculoskeletal Disorders and the Workplace: Low Back and Upper Extremities. Panel on Musculoskeletal Disorders and the Workplace. Washington, DC: National Academy Press; 2012. Commission on Behavioral and Social Sciences and Education.
    1. BLS Bureau of Labor Statistics (BLS) News Release. 2012. [Accessed July 12, 2014]. Available at .
    1. Anandacoomarasamy A, Caterson I, Sambrook P, Fransen M, March L. The impact of obesity on the musculoskeletal system. Int J Obes (Lond) 2008;32:211–22.
    1. Faghri PD, Momeni K. Musculoskeletal diseases, overweight and obesity, and aging workforce: how to encounter the problem. J Obes Wt Loss Ther. 2014;S4:e001.
    1. Nair LS. Prolotherapy for tissue repair. Transl Res. 2011;158(3):129–31.
    1. Hackett GS, Hemwall GA, Montgomery GA. Ligament and Tendon Relaxation Treated by Prolotherapy. 5th ed. Oak Park, IL: Gustav A. Hemwall; 1993.
    1. Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Prim Care. 2010;37:65–80.
    1. Schnirring L. Are your patients asking about prolotherapy? Physician Sportsmed. 2000;28(8):15–7.
    1. Kim SR, Stitik TP, Foye PM, Greenwald BD, Campagnolo DI. Critical review of prolotherapy for osteoarthritis, low back pain, and other musculoskeletal conditions: a physiatric perspective. Am J Phys Med Rehabil. 2004;83(5):379–89.
    1. Rabago D, Best TM, Beamsley M, Patterson J. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sport Med. 2005;15(5):376–80.
    1. Yelland MJ, Del Mar C, Pirozzo S, Schoene ML. Prolotherapy injections for chronic low back pain: a systematic review. Spine (Phila Pa 1976) 2004;29(19):2126–33.
    1. Dagenais S, Yelland MJ, Del Mar C, Schoene ML. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst Rev. 2007 Apr 18;2:CD004059.
    1. Best TM, Rabago D, Zgierska AE, Zeisig E, Ryan M, Crane D. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma. Br J Sports Med. 2009;43(7):471–81.
    1. Distel LM, Best TM. Prolotherapy: a clinical review of its role in treating chronic musculoskeletal pain. PM R. 2011;3(6 suppl 1):S78–81.
    1. Linetsky FS, Manchikanti L. Regenerative injection therapy for axial pain. Tech Reg Anesth Pain Manage. 2005;9:40–9.
    1. Adams E. Bibliography: Prolotherapy for Musculoskeletal Pain. Boston, MA: Veterans; 0000.
    1. Goswami A. Prolotherapy. J Pain Palliat Care Pharmacother. 2012;26:376–8.
    1. Alderman D, Alexander RW, Harris GR, Astourian PC. Stem cell prolotherapy in regenerative medicine: background, theory and protocols. J Prolotherapy. 2011;3(3):689–708.
    1. DeChellis DM, Cortazzo MH. Regenerative medicine in the field of pain medicine: prolotherapy, platelet-rich plasma therapy, and stem cell therapy-theory and evidence. Tech Reg Anesth Pain Manag. 2011;15(2):74–80.
    1. Reeves KD. Prolotherapy: injection of growth factors or growth factor production stimulants to growth normal cells or tissue. In: Waldman SD, editor. Pain Management. Philadelphia: Elsevier; 2006. pp. 1106–27.
    1. Creaney L, Hamilton B. Growth factor delivery methods of sports injuries: the state of play. Br J Sports Med. 2008;42:314–20.
    1. Martinez-Zapata MJ, Marti-Carvajal A, Sola I. Efficacy and safety of autologous plasma rich in platelets for tissue regeneration: a systematic review. Transfusion. 2009;49:44–56.
    1. Oh JH, Ha H, Yu MR, Lee HB. Sequential effects of high glucose on mesangial cell transforming growth factor-beta 1 and fibronectin synthesis. Kidney Int. 1998;54:1872–8.
    1. Fukuda K, Kawata S, Inui Y, et al. High concentration of glucose increases mitogenic responsiveness to heparin-binding epidermal growth factor-like growth factor in rat vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1997;17:1962–8.
    1. Woo SL, Hildebrand K, Watanabe N, et al. Tissue engineering of ligament and tendon healing. Clin Orthop Relat Res. 1999;367S:312–4.
    1. Tang JB, Xu Y, Ding F, Wang XT. Tendon healing in vitro: promotion of collagen gene expression by bFGF with NF-kB gene activation. J Hand Surg Am. 2003;28:215–20.
    1. Pugliese G, Pricci F, Locuratolo N, et al. Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions: relation to glucose-enhanced extracellular matrix production. Diabetologia. 1996;39:775–84.
    1. Reeves KD, Fullerton BD, Topol G. Evidence-based regenerative injection therapy (Prolotherapy) in sports medicine. In: Seidenberg PH, Beutler AI, editors. The Sports Medicine Resource Manual. Amsterdam: Elsevier; 2008. pp. 611–9.
    1. Vora A, Borg-Stein J, Nguyen RT. Regenerative injection therapy for osteoarthritis: fundamental concepts and evidence-based review. PM R. 2012;4:S104S–9.
    1. Sanchez M, Anitua E, Orive G. Platelet-rich therapies in treatment of orthopaedic sport injuries. Sports Med. 2009;39:345–54.
    1. Tabata Y. Tissue regeneration based on growth factor release. Tissue Eng. 2003;9:S5–15.
    1. Jensen KT, Rabago DP, Best TM, Patterson JJ, Vanderby R., Jr Early inflammatory response of knee ligaments to prolotherapy in a rat model. J Orthop Res. 2008;26:816–23.
    1. Jensen KT, Rabago DP, Best TM, Patterson JJ, Vanderby R., Jr Response of knee ligaments to prolotherapy in a rat injury model. Am J Sports Med. 2008;36:1347–57.
    1. Kim HJ, Kim SH, Yun DH. The effects of anti-inflammatory drugs on histologic findings of the experimental prolotherapy model. J Korean Acad Rehabil Med. 2006;30:378–84.
    1. Ahn KH, Kim HS, Lee WK. The effect of the prolotherapy on the injured Achilles tendon in a rat model. J Korean Acad Rehabil Med. 2002;26:332–6.
    1. Kim HS, Jeong TS, Wim WS. Comparison of histological changes in aacordance with the level of dextrose-concentration in experimental prolotherapy model. J Korean Acad Rehabil Med. 2003;27:935–40.
    1. Kim SA, Kim EH, Kim SY, et al. The effects of hyperosmolar dextrose and autologous serum injection in the experimental articular defect of rabbit. J Korean Acad Rehabil Med. 2006;30(2):173–8.
    1. Reeves KD. Prolotherapy: basic science, clinical studies, and technique. In: Lennard TA, editor. Pain Procedures in Clinical Practice (ed 2) Philadelphia, PA: Hanley and Belfus; 2000. pp. 172–90.
    1. Teasell RW, Mehta S, Aubut JA, et al. Spinal Cord Injury Rehabilitation Evidence Research Team A systematic review of pharmacologic treatments of pain after spinal cord injury. Arch Phys Med Rehabil. 2010;91(5):816–31.
    1. Krassioukov A, Eng JJ, Warburton DE, Teasell R, Spinal Cord Injury Rehabilitation Evidence Research Team A systematic review of the management of orthostatic hypotension after spinal cord injury. Arch Phys Med Rehabil. 2009;90(5):876–85.
    1. Moseley AM, Herbert RD, Sherrington C, Maher CG. Evidence for physiotherapy practice: a survey of the Physiotherapy Evidence Database (PEDro) Aust J Physiother. 2002;48:43–9.
    1. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52(6):377–84.
    1. Foley NC, Teasell RW, Bhogal SK, Speechley MR. Stroke rehabilitation evidence-based review: methodology. Top Stroke Rehabil. 2003;10:1–7.
    1. Deeks JJ, Dinnes J, D’Amico R, et al. Evaluating nonrandomized intervention studies. Health Technol Assess. 2003;7(27):iii–x. 1–173.
    1. Saunders LD, Soomro GM, Buckingham J, Jamtvedt G, Raina P. Assessing the methodological quality of nonrandomized intervention studies. West J Nurs Res. 2003;25:223–37.
    1. Sackett DL, Strauss SE, Richardson WS, Rosenberg W, Haynes RB. Evidence-based Medicine: How to Practice and Teach EBM. Edinburgh: Churchill Livingstone; 2000.
    1. Farrar JT, Young JP, Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149–58.
    1. Lee JS, Hobden E, Stiell IG, Wells GA. Clinically important change in the visual analog scale after adequate pain control. Acad Emerg Med. 2003;10:1128–30.
    1. Kovacs FM, Abraira V, Royuela A, et al. Minimal clinically important change for pain intensity and disability in patients with nonspecific low back pain. Spine. 2007;32:2915–20.
    1. Bombardier C, Hayden J, Beaton DE. Minimal clinically important difference: low back pain. Outcome measures. J Rheumatol. 2001;28:431–8.
    1. American College of Rheumatology . Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) – General Description. ACR; 2015. [Accessed March 3, 2015]. Available at .
    1. Sanderson LM, Bryant A. Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review. J Foot Ankle Res. 2015;8:57.
    1. Topol GA, Podesta LA, Reeves KD, Raya MF, Fullerton BD, Yeh HW. Hyperosmolar dextrose injection for recalcitrant Osgood–Schlatter disease. Pediatrics. 2011;128(5):e1121–8.
    1. Refai H, Altahhan O, Elsharkawy R. The efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: a preliminary prospective, randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg. 2011;69(12):2962–70.
    1. Comert Lilic S, Gungormus M. Is dextrose prolotherapy superior to placebo for the treatment of temporomandibular joint hypermobility? A randomized control trial. Int J Oral Maxillofac Surg. 2016 Feb 1; doi: 10.1016/j.ijom.2016.01.006. Epub ahead of print.
    1. Zhou H, Hu K, Ding Y. Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation. Br J Oral Maxillofac Surg. 2014;52(1):63–6.
    1. Yelland MJ, Sweeting KR, Lyftogt JA, Ng SK, Scuffham PA, Evans KA. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial. Br J Sports Med. 2011;45(5):421–8.
    1. Maxwell NJ, Ryan MB, Taunton JE, Gillies JH, Wong AD. Sonographically guided intratendinous injection of hyperosmolar dextrose to treat chronic tendinosis of the Achilles tendon: a pilot study. AJR Am J Roentgenol. 2007;189:w215–20.
    1. 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(4):1047–53.
    1. Lyftogt J. Prolotherapy and Achilles tendinopathy: a prospective pilot study of an old treatment. Aust Musculoskel Med J. 2005;10:16–9.
    1. Scarpone M, Rabago DP, Zgierska A, Arbogast G, Snell E. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med. 2008;18(3):248–54.
    1. Shin J, Seo K-M, Kim D-K, Kim B-K, Kang SH. The effect of prolotherapy on lateral epicondylitis of elbow. J Korean Acad Rehabil Med. 2002;26:764–8.
    1. Park JH, Song IS, Lee JB, et al. Ultrasonographic findings of healing of torn tendon in the patients with lateral epicondylitis after prolotherapy. J Korean Soc Med Ultrasound. 2003;22(3):177–83.
    1. Ryan M, Wong A, Rabago D, Lee K, Taunton J. Ultrasound-guided injections of hyperosmolar dextrose for overuse patellar tendinopathy: a pilot study. Br J Sports Med. 2011;45(12):972–7.
    1. Kim E, Lee JH. Autologous platelet-rich plasma versus dextrose prolotherapy for the threatment of chronic recalcitrant plantar fasciitis. PM R. 2014;6(2):152–8.
    1. Topol GA, Reeves KD. Regenerative injection of elite athletes with career-altering chronic groin pain who fail conservative treatment: a consecutive case series. Am J Phys Med Rehabil. 2008;87(11):890–902.
    1. Topol GA, Reeves KD, Hassanein KM. Efficacy of dextrose prolotherapy in elite male kicking-sport athletes with chronic groin pain. Arch Phys Med Rehabil. 2005;86:697–702.
    1. Bertrand H, Reeves KD, Bennett CJ, Bicknell S, Cheng AL. Dextrose prolotherapy versus control injections in painful rotator cuff tendinopathy. Arch Phys Med Rehabil. 2016;97(1):17–25.
    1. Lee DH, Kwack KS, Rah UW, Yoon SH. Prolotherapy for refractory rotator cuff disease: retrospective case-control study of 1-year follow-up. Arch Phys Med Rehabil. 2015;96(11):2027–32.
    1. Ryan MB, Wong AD, Gillies JH, Wong J, Traunton JE. Sonographically guided intratendinous injections of hyperosmolar dextrose/lidocaine: a pilot study for the treatment of chronic plantar fasciitis. Br J Sports Med. 2009;43:303–6.
    1. Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013;11(3):229–37.
    1. Rabago D, Mundt M, Zgierska A, Grettie J. Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: long term outcomes. Complement Ther Med. 2015;23(3):388–95.
    1. Reeves KD, 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;6:68–79.
    1. Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med. 2003;9(3):58–62.
    1. Dumais R, Benoit C, Dumais A, et al. Effect of regenerative injection therapy on function and pain in patients with knee osteoarthritis a randomized crossover study. Pain Med. 2012;13(8):990–9.
    1. 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(2):35–44.
    1. Hashemi M, Parviz J, Mennati S, et al. The effects of prolotherapy with hupertinic dextrose versus prolozone (interaarticular ozone) in patients with knee osteoarthritis. Anesth Pain Med. 2015;5(5):e27858.
    1. Reeves KD, 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;6:311–20.
    1. Jahangiri A, Moghaddam FR, 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(5):737–43.
    1. Miller MR, Mathews RS, Reeves KD. Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose. Pain Physician. 2006;9:115–21.
    1. Khan SA, Kumar A, Varshney MK. Dextrose prolotherapy for recalcitrant coccygodynia. J Orthop Surg. 2008;16:27–9.
    1. Kim WM, Lee HG, Jeong CW, Kim CM, Yoon MH. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. J Altern Complement Med. 2010;16(12):1285–90.
    1. Kim HS, Jung KH, Park IH, et al. Diagnosis and treatment of sacral asymlocation in back pain patients. Korean J Pain. 2007;20:130–7.
    1. Hooper RA, Yelland M, Fonstad P, Southern D. Prospective case series of litigants and non-litigants with chronic spinal pain treated with dextrose prolotherapy. Int Musculoskeletal Med. 2011;33(1):15–20.
    1. Centeno CJ, Elliott J, Elkins WL, Freeman M. Fluoroscopically guided cervical prolotherapy for instability with blinded pre and post radiographic reading. Pain Physician. 2005;8:67–72.
    1. Lee JD, Lee DW, Cheol Won J. Effects of intraarticular prolotherapy on sacroiliac joint pain. Korean J Pain. 2009;22:229–33.
    1. Kim MY, Na YM, Moon JH. Comparison on treatment effects of dextrose water, saline, and lidocaine for trigger point injections. J Korean Acad Rehabil Med. 1997;21:967–73.
    1. Khan KM, Cook JL, Bonar F, Harcourt P, Astrom M. Histopathology of tendinopathies. Update and implications for clinical management. Sports Med. 1999;27:393–408.
    1. Childress MA, Beutler A. Management of chronic tendon injuries. Am Fam Physician. 2013;87(7):486–90.
    1. Felson DT, Lawrence RC, Dieppe PA, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133(8):635–46.
    1. Wheaton M, Jensen N. The ligament injury connection to osteoarthritis. J Prolotherapy. 2010;2:294–304.
    1. Buckwalter JA, Brown TD. Joint injury, repair, and remodeling: roles in post-traumatic osteoarthritis. Clin Orthop Relat Res. 2004;(423):7–16.
    1. Borenstein DG. Chronic low back pain. Rheum Dis Clin North Am. 1996;22:439–56.
    1. Khan KM, Cook JL, Kannus P, Maffuli N, Bonar SF. Time to abandon the ‘tendinitis’ myth. BMJ. 2002;324:626–7.
    1. Alderman D. Prolotherapy for musculoskeletal pain. Pract Pain Manage. 2007:10–7.
    1. Ombregt L, Bisschop P, ter Veer HJ. A System of Orthopaedic Medicine. Second ed. London: Churchill Livingstone; 2003. p. 775.
    1. Frymoyer JW. Back pain and sciatica. N Engl J Med. 1988;318(5):291–300.
    1. Dreyfuss P, Dreyer SJ, Cole A, Mayo K. Sacroiliac joint pain. J Am Acad Orthop Surg. 2004;12(4):255–65.
    1. Carlson SW, Magee S, Carlson WO. An algorithm for the evaluation and treatment of sacroiliac joint dysfunction. S D Med. 2014;67(11):445–9. 451.
    1. Cher D, Polly D, Berven S. Sacroilliac joint pain: burden of disease. Med Devices (Auckl) 2014;7:73–81.
    1. Fortin JD, Vilensky JA, Merkel GJ. Can the sacro-iliac joint cause sciatica? Pain Physician. 2003;6(3):269–71.
    1. Poul-Goudzwaard AL, Vleeming A, Stoeckart R, Snijders CJ, Mens JM. Insufficient lumbopelvic stability: a clinical, anatomical, and biomechanical approach to “a specific” low back pain. Man Ther. 1998;3(1):12–20.
    1. Fortin JD, Aprill CN, Ponthieux B, Pier J. Sacroiliac joint: pain referral maps upon applying a new injection/arthrography technique. Part II: clinical evaluation. Spine. 1994;19(13):1483–9.
    1. Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet. 2010;376(9754):1751–67.
    1. Manchikanti L, Hirsch JA, Smith HS. Evidence-based medicine, systematic reviews, and guidelines in interventional pain management: part 2: randomized controlled trials. Pain Physician. 2008;11(6):717–73.
    1. Atkins D, Best D, Briss PA, et al. GRADE Working Group Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490.
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Schünemann HJ. GRADE: what is “quality of evidence” and why is it important to clinicians? BMJ. 2008;336:995–8.
    1. The Cochrane Collaboration . Cochrane Handbook for Systematic Reviews of Interventions. London: The Cochrane Collaboration; 2008.
    1. Manchikanti L, Benyamin RM, Falco FJE, Caraway DL, Datta S, Hirsch JA. Guidelines warfare over interventional techniques: is there a lack of discourse or straw man? Pain Physician. 2012;15:E1–26.
    1. Glasziou P, Chalmers I, Rawlins M, Mc- Culloch P. When are randomised trials unnecessary? Picking signal from noise. BMJ. 2007;334:349–51.
    1. Farrar JT, Portenoy RK, Berlin JA, Kinman J, Strom BL. Defining the clinically important difference in pain outcome measures. Pain. 2000;88:287–29.
    1. Afilalo M, Etropolski MS, Kuperwasser B, et al. Efficacy and safety of tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study. Clin Drug Investig. 2010;30(8):489–505.
    1. Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study. Expert Opin Pharmacother. 2010;11(11):1787–804.
    1. Binsfeld H, Szczepanski L, Waechter S, Richarz U, Sabatowski R. A randomized study to demonstrate noninferiority of once-daily OROS(®) hydromorphone with twice-daily sustained-release oxycodone for moderate to severe chronic noncancer pain. Pain Pract. 2010;10(5):404–15.
    1. Hale M, Khan A, Kutch M, Li S. Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain. Curr Med Res Opin. 2010;26(6):1505–18.
    1. AbbottLabs FDA Indications for 50% Dextrose. 2004. [Accessed November 12, 2014]. Available at .
    1. AbbottLabs . Approval Documentation for 25% Dextrose Submitted to FDA. Online Documentation. Chicago, IL: Abbott Laboratories; 1998.

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