Jump to:


The prevalence of chronic pain among adults in the US is 20.4%,1 a concomitant opioid epidemic and subsequent opioid-related deaths have created a national emergency.2 In addition the World Health Organization reports 1.71 billion people with musculoskeletal conditions worldwide. Musculoskeletal conditions can significantly limit function and are the leading cause of disability. National organizations have therefore called for new treatments of chronic pain and musculoskeletal conditions, including therapy that addresses the underlying pain pathology. Therapeutic injections with dextrose are increasingly used for this purpose.

Basic science and clinical research suggest several ways in which dextrose can reduce pain, improve overall function, and restore connective tissue function. Hypothesized mechanisms and clinical trials suggest injection with dextrose has the potential to 1) slow, halt or even reverse degenerative changes in ligaments, tendons, and joints, 2) simultaneously localize and treat primary nociceptive sources by precise diagnostic injection, 3) reduce peripheral sensitization in neuropathic pain, and 4) directly release nerve entrapment and reduce neurogenic inflammation without risk of anesthetic toxicity.3,4

Clinical trials have assessed three distinct therapeutic dextrose-related modalities and reported positive clinical effects compared with blinded injection controls.

  • Prolotherapy: Injection of hypertonic dextrose to treat chronic musculoskeletal pain.3 The purported mechanism focuses on proliferative repair.
  • Perineural injection treatment (PIT): The injection of dextrose adjacent to peripheral nerves to reduce neuropathic pain.5 The purported mechanism is associated with a sensorineural effect.
  • Hydrodissection: Dextrose is injected adjacent to peripheral nerves with continuous ultrasound guidance to release peripheral nerves from their encasing fascia in order to provide a decompressive effect.4

Each modality is in use as outpatient therapy in the U.S. Acquisition of these procedural skills is sometimes through formal medical training, but more often in continuing medical education contexts. Prolotherapy, PIT, and hydrodissection are supported for specific indications by a growing body of literature. The focus in this article is discussion of the evolving evidence base underpinning the therapeutic injection of dextrose.


Prolotherapy has been used in clinical practice since the 1950s and is supported by the strongest body of clinical evidence. It is also called regenerative injection therapy or proliferative therapy and involves the injection of dextrose into a joint, muscle, tendon, or other soft tissue area where it classically has been described as acting as an irritant to induce a local inflammatory response that triggers the natural healing cascade (proliferative phase of tissue repair).6 However, recent research in animal models has suggested that dextrose also stimulates proliferation via non-inflammatory mechanisms, as described later in this section.7,8

The ideal dextrose concentration in prolotherapy injections is still under investigation. Notable progress made was via an in vitro study done by Woo et el. comparing different concentrations and combinations of dextrose solutions in prolotherapy. Higher concentration of dextrose more than 5% induced cell apoptosis. 9 Wu et al (2022) also discussed that in vitro high glucose concentrations can mitigate TNF-α-induced NF-κB activation, upregulation of pro-inflammatory cytokines, and metabolic dysfunction. This study demonstrated that high glucose concentrations reduce inflammation-induced neurogenic deterioration, furthering the currently incomplete understanding of the effect of dextrose in wound healing cascade, proliferation, collagen deposition and tissue repair.10

The mechanisms of how dextrose injections work on physiologic and cellular levels in patients are not yet fully delineated. Proliferative effects of dextrose in fibroblasts have been studied in vivo using concentrations of dextrose that are hypertonic but not necessarily inflammatory. For example, Oh et al. reported that 10% dextrose injection, in contrast with a saline control injection, induced subsynovial tissue proliferation (ligament-equivalent proliferation) in a rabbit ligament model.7 A proliferative effect of dextrose on chondrocytes in stage IV human knee osteoarthritis was suggested by a clinical trial using pre-post arthroscopy. After intra-articular injection of 12.5% dextrose, biopsies within new areas of uptake of methylene blue confirmed a combination of fibro and hyaline-like cartilage on immunohistochemical staining.8

In the clinical realm, there is no standard of care for prolotherapy injection technique, concentration, or post-injection care at the time of this writing. Injection techniques can involve a peppering technique for tendon and ligament insertions, and for knee joint injections an infero-medial or infero-lateral approach seems to be preferred.6 Lidocaine is usually included with the dextrose to minimize discomfort from mechanical and chemical irritation to tissues, but even in low percentage, such as <0.5%, recent research indicates  muscular and neural toxicity effects of local anesthetic that may be counterproductive.11 Precise concentrations of dextrose in studies vary from 5-25%. It is common to advise patients to rest for 2-3 days to allow time for healing. With knee OA typical injection intervals are 4-6 weeks apart with a total of about 4 injections.6 However, intervals are varied for each indication and practitioner. Often, NSAIDs are avoided following an injection for several days as it can theoretically interfere with the proliferative repair mechanisms.3

There has been a marked increase of new randomized control trials, reviews and meta-analyses since 2019 as seen in table 1. Prolotherapy with dextrose continues to be shown in these usually small trials to be an effective therapy with clinical improvement of function and pain demonstrated in a wide array of clinical areas. Despite the growing number of supportive RCTs on this topic, there are no major society guidelines clearly recommending dextrose prolotherapy at the time of this writing. Of note, the American College of Rheumatology conditionally recommended against prolotherapy in 2019 for knee and hip osteoarthritis due to small, limited trials and study variability.12 However, as evidence is mounting in favor of Prolotherapy, many Sports Medicine training programs now include training in regenerative injection with dextrose or platelet rich plasma.13

Table 1 lists systemic reviews and meta analyses for Prolotherapy by author and year. The overall trend in these studies seems to indicate that Prolotherapy shows positive clinical outcomes for chronic musculoskeletal conditions including knee osteoarthritis,3,14-21 hand osteoarthritis,3,20  plantar fasciopathy,3,22-25 lateral epicondylitis,3,24,26-28 rotator cuff tendinopathy,3,24,29-31 Osgood-Schlatter disease,3,25 Achilles tendinopathy,3,24,25,32 and temporomandibular joint dysfunction.24,33 None of these systemic reviews or meta-analyses demonstrated any significant adverse events due to injection of dextrose.

Based on a variety of measurement outcomes, dextrose prolotherapy still appears to be a promising alternative injection-based intervention. Nonetheless, there are significant limitations of the current body of research including heterogeneity of study designs, non-standardized injection techniques, and small sample size, which could contribute to varied interpretations of the results. More high quality research will be important to advance the use of prolotherapy for the many patients presenting with pain and musculoskeletal conditions.

Prolotherapy Table 1

Table one lists the systemic reviews and meta analyses by author and year with summarized evidences. The number of random trials is listed along with area of body: e.g., knee OA (8) Indicates that eight trials were included in the review.

S- systemic review; M- meta-analysis; DP – dextrose prolotherapy; HDP – hypertonic dextrose prolotherapy, HA – hyaluronic acid 

WMD- weighted mean difference; SMD – standardized mean difference visual analog scale (VAS) pain score, foot function index (FFI), American Orthopaedic Foot and Ankle Society (AOFAS) score.

Perineural Injection Treatment

Perineural injections are an ultrasound guided technique used to inject medication adjacent to nerves, with the goal to reduce neuropathic pain. They have been performed classically with injectates including lidocaine, which has a short duration of action, and steroids, which have multiple associated risks. Dr. John Lyftogt anecdotally observed that injection of subcutaneous dextrose without local anesthetic over painful sensory nerves resulted in prompt elimination of hyperalgesia and allodynia in the area of injection.5 Perineural injection with dextrose has been used since then to target the peripheral nerve as a pain generator in chronic pain syndromes. The mechanism of action is thought to be related to an effect on neuropathic pain generators rather than proliferation.34 Note that this injection technique and hydrodissection, discussed in the next section, both involve injection of medication perineurally, thus PIT injections innately incorporate a more superficial level of hydrodissection. It is better to think of them as two mechanisms by which the same injection can provide pain relief.

To understand the mechanism of PIT injections, an understanding of the relationship between neuroinflammation and chronic pain is important and is briefly reviewed here. Upregulation of inflammatory mediators produced by acute changes after injury, including prostaglandins, nerve growth factor, bradykinin, interleukins, and tumor necrosis factor alpha modulate transient receptor potentials, sodium and piezo ion channels on central and peripheral nerves (predominantly peptidergic C fibers), and may result in a transition from acute to chronic pain.35 This transition to chronic pain is characterized by the self-perpetuating production and release of pain-producing and degenerative neuropeptides. These neuropeptides commonly include substance P and calcitonin gene related peptide (CGRP). The production and release of these neuropeptides by activated C fibers is termed neurogenic inflammation and is characterized by an absence of leukocytes.35 It is hypothesized that PIT injection therapy with dextrose has a rapid neurogenic effect on these pain-producing C fibers following injection.

Recent double blind RCT studies have been performed to show that perineural injection with dextrose is effective in various neuropathies. Studies have shown that PIT with dextrose is similar or better than steroid or saline injection in ulnar neuropathy at the elbow36,37 and better than saline for caudal epidural injection when assessing long-term follow up34. The number of studies on PIT with dextrose are still growing, and there are no meta-analyses at the time of this writing.

Hydrodissection Effects Using Dextrose

Hydrodissection refers to ultrasound guided injection using an injectate to mechanically release and decompress an entrapped nerve. Entrapment of nerves occurs at various sites in the body between two muscles, between muscle and bone, across joints, around blood vessels and through fascial tunnels. Compression of the nerve at these entrapment sites causes compressive neuropathies. As ultrasound imaging improves, pain due to nerve entrapment at classic and non-classic locations is being increasingly suspected as a contributor to chronic pain maintenance. In 2003 Bennett described three rat models used to study neuropathic pain: partial sciatic ligation model, chronic constriction injury model, and spinal nerve ligation model.38 The partial sciatic ligation model describes non-compressive contact of a ligature with the sciatic nerve resulting in functional nerve disruption and associated nerve swelling.38 This model supports the concept that even minimal compression of a nerve within the surrounding soft tissues can result in clinically important neurogenic inflammation and neuropathic pain.5 Hydrodissection can be performed with many injectates all aiming to target mechanical compression as well as neurogenic inflammation. Hydrodissection with dextrose has been increasingly studied as a safer and longer lasting option compared to lidocaine or steroid injections. In addition, there is increasing interest in studying hydrodissection without an anesthetic in order to preserve motor function.39

Carpal tunnel syndrome is the most common compressive neuropathy and has been the most studied area for hydrodissection. In 2018 Wu et al. demonstrated the benefits of mechanical tissue separation around nerves by comparing hydrodissection of the median nerve to subcutaneous injection with normal saline.40 Hydrodissection alone was found to be superior.41

There have been many further studies on hydrodissection that compare various injectates including dextrose. Most commonly an isotonic solution of 5% dextrose (D5W) is used. A proposed yet still uncertain mechanism of action of dextrose suggests that dextrose downregulates the TRPV-1 receptor which is upregulated in chronic pain. Another mechanism is theorized to be decrease of C-fiber activation which is increased in a hypoglycemic state.42 Two favorable systematic reviews included D5W as an injectate for hydrodissection in compressive neuropathy found that D5W showed consistently favorable outcomes in pain reduction, functional scales, cross sectional area reduction on ultrasound, and EMG findings compared to control and steroid groups. However, all of the 10 RCTs included compared different interventions with different factors and none could be matched for meta-analysis. In addition, the follow-up interval and volume of injectate varies greatly among studies limiting interpretation. All of the studies with dextrose involved the median nerve with entrapment at the carpal tunnel.42

While carpal tunnel syndrome is the most consistently studied entrapment, there have been RTCs looking at other areas of the body. To emphasize the potential generalizability of hydrodissection for neurogenic pain, Lam et al. hydrodissected a variety of nerves or ganglia in the upper body (stellate ganglion, brachial plexus, cervical nerve roots, and paravertebral spaces) in participants with severe neuropathic pain, and pain reduction exceeded 50% in all 26 participants and 75% in half of the participants.43 This high volume hydrodissection used only dextrose, and so had no lidocaine toxicity risk.

Comparisons of differing volumes of dextrose injections for carpal tunnel syndromes have also been made. The Lin group concludes that injection with dextrose of 4 mL provides better functional outcome and pain relief vs 1ml or 2ml.44,45 Further expansion of the perineural space and longitudinal drug spreading was observed with higher volume. Thus, dextrose hydrodissection appears to offer both mechanical hydrodissection and sensorineural effects in carpal tunnel syndrome.

Summary/ Cutting Edge Issues

Basic science and clinical studies suggest beneficial therapeutic effects of dextrose in conditions associated with tendinopathies, fasciopathies, osteoarthritis, neuropathic pain, and in the presence of nerve entrapment. A substantial percentage of those with idiopathic neuropathy may have symptom magnification due to the “double crush” effect caused by compression of vulnerable nerves. Treatment of those vulnerable nerves to reduce symptoms of neuropathy is a fertile ground for clinically important research. In addition, since research suggests that dextrose can act as an analgesic, it can be used for hydrodissection without anesthetic.43 Its use in therapeutic nerve blocks may facilitate diagnostic and therapeutic injection while preventing lidocaine-induced weakness or toxicity.11,43,44 Additionally, Prolotherapy injections are increasingly being used worldwide in low to middle-income countries due to their low-cost and ease of injection.46

Given the potential benefits for chronic pain and the favorable safety profile the clinical use for these injections is rapidly expanding. Dextrose injections are just starting to be studied in the treatment of GU dysfunction and PTSD. An ongoing RCT by Beco et al. uses perineural injections of dextrose 5% in sterile water (D5W) targeting obturator nerve for longstanding lower urinary tract symptoms and/or dyspareunia 47 Beco et al.’s. recent publication suggests good relief urinary symptoms of patient with obturator neuralgia.47 A case report by Reeves et al. showed bilateral cervical plexus hydrodissection with 10 mL DW5 had profound clinical and emotional improvement of a disabled veteran due to severe post-traumatic stress disorder (PTSD), who failed years of standard treatments.48

Other emerging clinical indications for prolotherapy include low back pain, sacroiliac joint (SIJ) pain and joint laxity.49 For low back pain various studies do not show superiority of prolotherapy alone compared to control, however, there does seem to be a benefit to prolotherapy when performed in conjunction with other standard interventions. Studies on prolotherapy for SIJ pain are more promising, showing significant improvements in function and pain with longer lasting effect than steroid.49 Many studies exist involving temporomandibular joint dysfunction some of which evaluate laxity of the joint in addition to pain and demonstrate decreased locking and hypermobility. There are a limited number of studies examining prolotherapy on laxity of other joints such as ACL laxity and lumbar spine instability. Results are promising but there is not yet enough data to determine the benefits of prolotherapy for joint laxity.49

Gaps in Knowledge/ Evidence Base

The usage of dextrose in prolotherapy, PIT, and hydrodissection continues to expand. Dextrose injections are a promising alternative treatment for long-standing clinical problems unsolvable by current standards of treatment. However, the current body of research is limited by small effect sizes and inability to generalize results due to highly varied injection schedules, injection sites, dextrose concentrations, controls and comparators studied. Additionally, proliferation has not been confirmed as a key component of clinical improvement in Prolotherapy, although it has seldom been directly measured.10,50

The safety of dextrose injection is supported by a growing number of small but methodologically rigorous clinical studies across many pain conditions.3,12 Since 2005 all meta-analyses have reported safety across various indications. Discussion of treatment options with patients should include mention of dextrose-based therapies, given the amount of level B evidence in evidence-based literature.51 Each type of therapeutic dextrose injection can be appropriate for carefully selected chronic pain patients, many of whom have “tried everything” and risk sliding into chronic opioid-based care. Providers should remain alert to new guidelines and be sensitive to patient preferences. It will be important to emphasize ultrasound education in training so that clinicians will have the skill set required to safely incorporate such injection techniques in the future. Further research in these techniques, especially PIT and hydrodissection, is requisite and will help guide their clinical application.


  1. Dahlhamer J, Lucas J, Zelaya C, Nahin R, Mackey S, DeBar L, Kerns R, Von Korff M, Porter L, Helmick C. Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults – United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(36):1001-1005.
  2. Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and Opioid-Involved Overdose Deaths – United States, 2013-2017. MMWR Morb Motal Wkly Rep. 2018;67(5152):1419-1427.
  3. Reeves KD, Sit RWS, Rabago D. Dextrose prolotherapy: A narrative review of basic science and clinical research, and best treatment recommendations. Phys Med Rehabil Clin N Am. 2016;27(4):783-823.
  4. Wu YT, Ho TY, Chou YC, Ke MJ, Li TY, Tsai CK, Chen LC. Six-month efficacy of perineural dextrose for carpal tunnel syndrome: A prospective, randomized, double-blind, controlled trial. Mayo Clin Proc. 2017;92(8):1179-1189.
  5. Lyftogt J. Pain conundrums: which hypothesis? Central nervous system sensitization versus peripheral nervous system autonomy. Australasian Musculoskeletal Medicine. 2008;13(11):72-74.
  6. Zhao AT, Caballero CJ, Nguyen LT, Vienne HC, Lee C, Kaye AD. A Comprehensive Update of Prolotherapy in the Management of Osteoarthritis of the Knee. Orthop Rev (Pavia). 2022;14(4):33921. Published 2022 May 31. Doi:10.52965/001c.33921
  7. Oh S, Ettema AM, Zhao C, Zobitz ME, Wold LE, An KN, Amadio PC. Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: A potential model to study carpal tunnel syndrome? Hand (N Y). 2008;3(1):34-40.
  8. Topol GA, Podesta LA, Reeves KD, Giraldo MM, Johnson LJ, Grasso R, Jamín A, Clark T, Rabago D. The chondrogenic effect of intra-articular hypertonic-dextrose (prolotherapy) in severe knee osteoarthritis. PMR. 2016;8(11):1072-1082.
  9. Woo MS, Park J, Ok SH, et al. The proper concentrations of dextrose and lidocaine in regenerative injection therapy: in vitro study. Korean J Pain. 2021;34(1):19-26. Doi:10.3344/kjp.2021.34.1.19
  10. Wu Z, Tu X, Tu Z. Hyperosmolar dextrose injection for Osgood-Schlatter disease: a double-blind, randomized controlled trial. Arch Orthop Trauma Surg. 2022;142(9):2279-2285. Doi:10.1007/s00402-021-04223-1
  11. Perez-Castro R, Patel S, Garavito-Aguilar ZV, Rosenberg A, Recio-Pinto E, Zhang J, Blanck TJ, Xu F. Cytotoxicity of local anesthetics in human neuronal cells. Anesth Analg. 2009 Mar;108(3):997-1007. doi: 10.1213/ane.0b013e31819385e1
  12. Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, Callahan L, Copenhaver C, Dodge C, Felson D, Gellar K, Harvey WF, Hawker G, Herzig E, Kwoh CK, Nelson AE, Samuels J, Scanzello C, White D, Wise B, Altman RD, DiRenzo D, Fontanarosa J, Giradi G, Ishimori M, Misra D, Shah AA, Shmagel AK, Thoma LM, Turgunbaev M, Turner AS, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020 Feb;72(2):149-162. Doi: 10.1002/acr.24131. Epub 2020 Jan 6. Erratum in: Arthritis Care Res (Hoboken). 2021 May;73(5):764. PMID: 31908149.
  13. Zaremski JL, Diamond MC, Aagesen A, et al. Musculoskeletal and Sports Medicine Physical Medicine and Rehabilitation Curriculum Guidelines. PM&R. 2017;9(12):1244-1267. doi:10.1016/j.pmrj.2017.07.006
  14. Arias-Vázquez PI, Tovilla-Zárate CA, Castillo-Avila RG, et al. Hypertonic Dextrose Prolotherapy, an Alternative to Intra-Articular Injections With Hyaluronic Acid in the Treatment of Knee Osteoarthritis: Systematic Review and Meta-analysis. Am J Phys Med Rehabil. 2022;101(9):816-825. Doi:10.1097/PHM.0000000000001918
  15. Wang J, Liang J, Yao J, et al. Meta-analysis of clinical trials focusing on hypertonic dextrose prolotherapy (HDP) for knee osteoarthritis. Aging Clin Exp Res. 2022;34(4):715-724. Doi:10.1007/s40520-021-01963-3
  16. Chen YW, Lin YN, Chen HC, Liou TH, Liao CD, Huang SW. Effectiveness, Compliance, and Safety of Dextrose Prolotherapy for Knee Osteoarthritis: A Meta-Analysis and Metaregression of Randomized Controlled Trials. Clin Rehabil. 2022;36(6):740-752. Doi:10.1177/02692155221086213
  17. Cortez VS, Moraes WA, Taba JV, et al. Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review. Clinics (Sao Paulo). 2022;77:100037. Published 2022 May 17. Doi:10.1016/j.clinsp.2022.100037
  18. OrthoEvidence. Evidence-Based Use of Dextrose Prolotherapy for Knee Osteoarthritis:  A Meta-analysis of Randomized Trials. OE Original. 2021;4(4):3. Available from: https://myorthoevidence.com/Blog/Show/124
  19. Wee TC, Neo EJR, Tan YL. Dextrose prolotherapy in knee osteoarthritis: A systematic review and meta-analysis. J Clin Orthop Trauma. 2021;19:108-117. Published 2021 May 20. Doi:10.1016/j.jcot.2021.05.015
  20. Hung CY, Hsiao MY, K.V. C, Han DS, Wang TG. Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis. J Pain Res. 2016;9:847-857.
  21. Sit RWS, Chung VCH, Reeves KD, Rabago D, Chan KKW, Chan DCC, Wu X, Ho RST, Wong SYS. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis. Sci Rep. 2016;6:25247.
  22. Chutumstid T, Susantitaphong P, Koonalinthip N. Effectiveness of dextrose prolotherapy for the treatment of chronic plantar fasciitis: A systematic review and meta-analysis of randomized controlled trials [published online ahead of print, 2022 Mar 25]. PM R. 2022;10.1002/pmrj.12807. doi:10.1002/pmrj.12807
  23. Lai WF, Yoon CH, Chiang MT, et al. The effectiveness of dextrose prolotherapy in plantar fasciitis: A systemic review and meta-analysis. Medicine (Baltimore). 2021;100(51):e28216. Doi:10.1097/MD.0000000000028216
  24. Chung MW, Hsu CY, Chung WK, Lin YN. Effects of dextrose prolotherapy on tendinopathy, fasciopathy, and ligament injuries, fact or myth?: A systematic review and meta-analysis. Medicine (Baltimore). 2020;99(46):e23201. Doi:10.1097/MD.0000000000023201
  25. 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;Oct 20(8):57.
  26. Zhu M, Rabago D, Chung VC, Reeves KD, Wong SY, Sit RW. Effects of Hypertonic Dextrose Injection (Prolotherapy) in Lateral Elbow Tendinosis: A Systematic Review and Meta-analysis [published online ahead of print, 2022 Feb 28]. Arch Phys Med Rehabil. 2022;S0003-9993(22)00240-4. Doi:10.1016/j.apmr.2022.01.166
  27. Arias-Vázquez PI, Castillo-Avila RG, Tovilla-Zárate CA, Quezada-González HR, Arcila-Novelo R, Loeza-Magaña P. Efficacy of prolotherapy in pain control and function improvement in individuals with lateral epicondylitis: A Systematic Review and Meta-analysis. Efficacy of prolotherapy in pain control and function improvement in individuals with lateral epicondylitis: A Systematic Review and Meta-analysis. ARP Rheumatol. 2022;1(2):152-167.
  28. Dong W, Goost H, Lin XB, Burger C, Paul C, Wang ZL, Kong FL, Welle K, Jiang ZC, Kabir K. Injection therapies for lateral epicondylalgia: a systematic review and Bayesian network meta-analysis. Br J Sports Med. 2016;50(15):900-908.
  29. Arias-Vázquez PI, Tovilla-Zárate CA, González-Graniel K, et al. Efficacy of hypertonic dextrose infiltrations for pain control in rotator cuff tendinopathy: systematic review and meta-analysis. Efficacy of hypertonic dextrose infiltrations for pain control in rotator cuff tendinopathy: systematic review and meta-analysis. Acta Reumatol Port. 2021;46(2):156-170.
  30. Catapano M, Zhang K, Mittal N, Sangha H, Onishi K, de Sa D. Effectiveness of Dextrose Prolotherapy for Rotator Cuff Tendinopathy: A Systematic Review [published correction appears in PM R. 2020 Oct;12(10):1064]. PM R. 2020;12(3):288-300. Doi:10.1002/pmrj.12268
  31. Lin MT, Chiang CF, Wu CH, Huang YT, Tu YK, Wang TG. Comparative Effectiveness of Injection Therapies in Rotator Cuff Tendinopathy: A Systematic Review, Pairwise and Network Meta-analysis of Randomized Controlled Trials. Arch Phys Med Rehabil. 2019;100(2):336-349.
  32. Morath O, Kubocsh EJ, Taeymans J, Zwingmann J, Konstantinidis L, Südkamp NP, Hirschmüller A. The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy – a systematic review including meta-analysis. Scand J Med Sci Sports. 2018;28(1):4-15.
  33. Nagori SA, Jose A, Gopalakrishnan V, Roy ID, Chattopadhyay PK, Roychoudhury A. The efficacy of dextrose prolotherapy over placebo for temporomandibular joint hypermobility: A systematic review and meta-analysis. J Oral Rehabil. 2018;Jul 19 doi: 10.1111/joor.12698. [Epub ahead of print].
  34. Maniquis-Smigel L, Reeves KD, Rosen JH, Coleman C, Lyftogt J, Cheng AL, Rabago D. Analgesic effect and potential cumulative benefit from caudal epidural D5W in consecutive participants with chronic low back and buttock/leg pain. Jnl Alt Compl Med. 2018 12(12):1189-1196.Yoshii Y, Zhao C, Schmelzer JD, Low PA, An KN, Amadio PC. Effects of hypertonic dextrose injections in the rabbit carpal tunnel. J Orthop Res. 2011;29(7):1022-1027.
  35. Ji R, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology. 2018;192(2):343-366.
  36. Chen LC, Ho TY, Shen YP, Su YC, Li TY, Tsai CK, Wu YT. Perineural Dextrose and Corticosteroid Injections for Ulnar Neuropathy at the Elbow: A Randomized Double-blind Trial. Arch Phys Med Rehabil. 2020 Aug;101(8):1296-1303. Doi: 10.1016/j.apmr.2020.03.016. Epub 2020 Apr 20. PMID: 32325164.
  37. Mansiz-Kaplan B, Nacir B, Pervane-Vural S, Tosun-Meric O, Duyur-Cakit B, Genc H. Effect of Perineural Dextrose Injection on Ulnar Neuropathy at the Elbow: A Randomized, Controlled, Double-Blind Study. Arch Phys Med Rehabil. 2022 Jun 9:S0003-9993(22)00403-8. Doi: 10.1016/j.apmr.2022.04.013. Epub ahead of print. PMID: 35690093.
  38. Bennett GJ, Chung JM, Honore M, Seltzer Z. Models of neuropathic pain in the rat. Curr Protoc Neurosci. 2003;Chapter 9:Unit 9.14.
  39. Wu YT, Lam KHS, Lai CY, Chen SR, Shen YP, Su YC, Li TY, Wu CH. Novel Motor-Sparing Ultrasound-Guided Neural Injection in Severe Carpal Tunnel Syndrome: A Comparison of Four Injectates. Biomed Res Int. 2022 Feb 17;2022:9745322. Doi: 10.1155/2022/9745322. PMID: 35224104; PMCID: PMC8872692.
  40. Wu YT, Ke MJ, Ho TY, Li TY, Shen YP, Chen LC. Randomized double-blinded clinical trial of 5% dextrose versus triamcinolone injection for carpal tunnel syndrome patients. Ann Neurol. 2018;84(4):601-610.
  41. Wu YT, Chen SR, Li TY, Ho TY, Shen YP, Tsai CK, Chen LC. Nerve hydrodissection for carpal tunnel syndrome: A prospective, randomized, double-blind, controlled trial. Muscle Nerve. 2019;59(2):174-180.
  42. Buntragulpoontawee M, Chang KV, Vitoonpong T, Pornjaksawan S, Kitisak K, Saokaew S, Kanchanasurakit S. The Effectiveness and Safety of Commonly Used Injectates for Ultrasound-Guided Hydrodissection Treatment of Peripheral Nerve Entrapment Syndromes: A Systematic Review. Front Pharmacol. 2021 Mar 5;11:621150. Doi: 10.3389/fphar.2020.621150. PMID: 33746745; PMCID: PMC7973278.
  43. Lam SKH, Reeves KD, Cheng AL. Transition from deep regional blocks toward deep nerve hydrodissection in the upper body and torso. Method description and results from a retrospective chart review of the analgesic effect of 5% dextrose water as the primary hydrodissection injectate. Biomed Res Int 2017;7920438 (Available at https://www.hindawi.com/journals/bmri/2017/7920438/).
  44. Lin MT, Liao CL, Hsiao MY, Hsueh HW, Chao CC, Wu CH. Volume Matters in Ultrasound-Guided Perineural Dextrose Injection for Carpal Tunnel Syndrome: A Randomized, Double-Blinded, Three-Arm Trial. Front Pharmacol. 2020 Dec 17;11:625830. Doi: 10.3389/fphar.2020.625830. PMID: 33391002; PMCID: PMC7773892.
  45. Lin MT, Liu IC, Syu WT, Kuo PL, Wu CH. Effect of Perineural Injection with Different Dextrose Volumes on Median Nerve Size, Elasticity and Mobility in Hands with Carpal Tunnel Syndrome. Diagnostics (Basel). 2021 May 9;11(5):849. Doi: 10.3390/diagnostics11050849. PMID: 34065073; PMCID: PMC8150286.
  46. Rabago D, Reeves KD, Doherty MP, Fleck M. Prolotherapy for Musculoskeletal Pain and Disability in Low- and Middle-Income Countries. Phys Med Rehabil Clin N Am. 2019;30(4):775-8610.1016/j.pmr.2019.07.003.
  47. Beco J, Mouchel J. Perineural dextrose injections in the treatment of lower urinary tract symptoms and dyspareunia induced by obturator neuralgia. Med Hypotheses. 2020 Nov;144:109991. Doi: 10.1016/j.mehy.2020.109991. Epub 2020 Jun 11. PMID: 32570164.
  48. Reeves KD, Shaw J, McAdam R, Lam KHS, Mulvaney SW, Rabago D. A Novel Somatic Treatment for Post-traumatic Stress Disorder: A Case Report of Hydrodissection of the Cervical Plexus Using 5% Dextrose. Cureus. 2022 Apr 7;14(4):e23909. Doi: 10.7759/cureus.23909. PMID: 35411286; PMCID: PMC8988854.
  49. Hsu C, Vu K, Borg-Stein J. A narrative Review of Mechanisms, Techniques, and Protocols, and Evidence for Common Musculoskeletal Conditions. Phys Med Rehabil Clin N Am. 2022 Oct 17; DOI:https://doi.org/10.1016/j.pmr.2022.08.011
  50. Rabago D, Kijowski R, Woods M, Patterson JJ, Mundt M, Zgierska A, Grettie J, Lyftogt J, Fortney L. Association between disease-specific quality-of-life and magnetic resonance imaging outcomes in a clinical trial of prolotherapy for knee osteoarthritis. Arch Phys Med Rehabil. 2013;94(11):2075-2082.
  51. Burns PB, Rohrick RJ, Chung KC. The Levels of Evidence and their role in Evidence-Based Medicine. Plast Reconstr Surg. 2011;128(1):305-310.

Original Version of the Topic

K. Dean Reeves, MD, David Rabago, MD. Therapeutic Injection of Dextrose: Prolotherapy, Perineural Injection Therapy and Hydrodissection 10/24/2019

Author Disclosure

Mooyeon Oh-Park, MD
Nothing to Disclose

Emma Desjardins, DO
Nothing to Disclose

Areeb Chator, MD
Nothing to Disclose

Lili Wang, DO
Nothing to Disclose

Dean Reeves, MD
Nothing to Disclose