Author(s): Chaitanya Konda, DO, Ammar Khan, MD, Victoria Noel, MD, Dean Reeves, MD, David Rabago, MD
Originally published: October 24, 2019 Last updated: November 20, 2025
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Introduction

The prevalence of chronic pain among adults in the US is 20.4%.1 In 2022 the World Health Organization reported 1.71 billion people with musculoskeletal conditions. Musculoskeletal conditions can lead to reduced ability to participate in the workforce and are the biggest contributor to years lived with disability worldwide. National organizations have 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.2

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

  • Prolotherapy: An injection therapy in which high concentration dextrose is injected into ligament and joint entheses, joint spaces, or fascia to treat chronic musculoskeletal pain.
  • Perineural injection treatment (PIT): Injection of low concentration dextrose adjacent to peripheral nerves to treat neuropathic pain; reported mechanisms include reduction of neurogenic inflammation.3
  • Hydrodissection: Injection adjacent to peripheral nerves with continuous ultrasound guidance to release peripheral nerves from their encasing fascia to provide a decompressive effect.

All these modalities are currently used in outpatient settings and the subject of ongoing research. The focus in this article is discussion of the evolving evidence base underpinning the therapeutic injection of dextrose.

Prolotherapy

Prolotherapy has been used in clinical practice since the 1950s and, of the three, 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).5 Prolotherapy may induce tissue remodeling via stimulating growth factors.4

Clinically, no formal medical society has published a unified set of protocols for major anatomical areas, joints, or indications; however, there are at least three texts that have framed clinical use. Teaching of prolotherapy has been through collegial interaction, service-learning organizations, and ACGME-accredited residency and fellowship programs. Dextrose is injected in concentrations ranging from 12.5% to 25%. Lower concentrations (e.g., 5%) may be used for perineural injections but are less typical in prolotherapy. Dextrose solution is typically commercially available at 50%. To achieve a lower concentration, it is diluted with saline or sterile water. For patient comfort, lidocaine or bupivacaine anesthetic blebs can be applied prior to injection of deeper structures. The provider then injects the dextrose solution directly into the ligament, tendon, joint capsule, or other connective tissues, often under ultrasound guidance.

Injections are often done at multiple points around the affected structure in an effort to treat nociceptive sources more completely and maximize the stimulus for healing. It is common to advise patients to rest for 2-3 days to allow time for healing. There are often multiple rounds of injections for various musculoskeletal pathologies, this varies significantly by provider. Patients are often advised to avoid NSAIDs following an injection for several days as it can theoretically interfere with the proliferative repair mechanisms.2

Randomized controlled trials have compared dextrose injection to active control therapy, typically saline or free water. The strongest efficacy evidence comprises RCTs and meta- analyses for prolotherapy in knee OA. Prolotherapy has also been compared in effectiveness studies to injectates such as lidocaine and corticosteroids. Outcomes are mixed; currently, the strongest evidence reporting dextrose prolotherapy as superior to corticosteroid injection exists for sacroiliac joint pain.6 For lateral epicondylosis, plantar fasciitis, rotator cuff tendinopathy, and chronic subacromial bursitis, available RCTs do not demonstrate overall superiority in pain or function outcomes over corticosteroids,7,8,9 although dextrose injection may have a superior side effect profile. Other musculoskeletal conditions for which multiple RCTs have shown favorable but variable (level B) evidence of clinical efficacy of prolotherapy compared to a variety of control treatments include hand osteoarthritis, temporomandibular joint (TMJ) laxity, and Osgood Schlatter disease. Federal and foundation funding for prolotherapy is limited; only one basic science study and two clinical trials have been funded by the National Institutes of Health for prolotherapy. The self-funded nature of prolotherapy research slows the speed and size of prolotherapy research.

There are no major society guidelines clearly recommending dextrose prolotherapy at the time of this writing. Physicians interested in prolotherapy often pursue supplemental training through medical societies or professional organizations, rather than learning this injection technique in fellowship or residency. Dextrose prolotherapy is a promising alternative injection-based intervention. Nonetheless, there are significant limitations to 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.

Perineural Injection Treatment

Perineural injection treatment (PIT) is an ultrasound guided technique used to inject medication adjacent to nerves, with the goal of reducing neuropathic pain. Dextrose 5% is injected into space adjacent to the affected nerve. PIT has previously been performed with lidocaine and/or steroids. It has anecdotally been observed that injection of subcutaneous dextrose without local anesthetic resulted in prompt elimination of hyperalgesia and allodynia around the injection site.10 Perineural injection with dextrose has been used since this discovery to target peripheral nerves as pain generators in chronic neuropathic pain. 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.

Wet needling refers to the injection of a pharmacological substance (such as local anesthetic, corticosteroid, botulinum toxin, platelet-rich plasma, or other agents) into muscle or soft tissue using a needle, typically targeting myofascial trigger points or areas of musculoskeletal pain. This 2024 prospective nonrandomized study by Jacob and Sankaran compared wet needling (WN) and dextrose prolotherapy (DPT) for chronic myofascial pain, evaluating pain, disability, and trigger point count over a 24-month period.11 Involving 200 patients, it found that while both treatments were effective in the short term, DPT produced significantly greater and longer- lasting reductions in pain (using the Visual Analogue Scale), disability (using the Oswestry Disability Index), and myofascial trigger point counts than WN, particularly at the 3-month and 24-month marks. The study highlights how DPT, through a controlled inflammatory response, may offer superior tissue remodeling compared to the macro- trauma effect of WN. Although limited by self-selection, lack of blinding, and a single-center design, its findings suggest that even a single dextrose injection can yield durable improvements. This is particularly relevant to perineurial injection treatment (PIT), which uses low- concentration dextrose to modulate neurogenic inflammation at the nerve interface. The study’s support for dextrose’s long-term efficacy in soft tissue pain syndromes strengthens the rationale for PIT, as both therapies rely on similar mechanisms—targeted glucose-induced resolution of neuroinflammation and tissue repair—making DPT’s outcomes a valuable translational model for broader applications like PIT in chronic neuropathic or neurogenic pain conditions.

Double-blind randomized controlled trials demonstrate that perineural injection with 5% dextrose is effective for both ulnar neuropathy at the elbow and carpal tunnel syndrome, with superior or comparable improvements in pain, function, and nerve morphology compared to corticosteroid injections.12,13 There are currently no double-blind randomized controlled trials in the medical literature investigating the use of perineural injection with dextrose for neuropathic pain conditions beyond carpal tunnel syndrome and ulnar neuropathy at the elbow.

Hydrodissection

Hydrodissection with dextrose is an ultrasound-guided interventional technique used for pain management, particularly in conditions such as myofascial pain syndrome and peripheral nerve entrapment. The procedure involves the injection of a dextrose solution—most commonly 5% or 10% dextrose in water—into interfascial or perineural spaces to mechanically separate nerves or fascial planes, thereby relieving compression and associated pain. This approach is considered when conventional treatments, such as physical therapy, oral analgesics, or corticosteroid injections, have failed to provide adequate relief.14,15

The analgesic effect of dextrose hydrodissection is attributed to both mechanical and biochemical mechanisms. Mechanically, the injectate disrupts adhesions and decompresses the nerve, improving its function and reducing pain. Biochemically, dextrose is thought to modulate neurogenic inflammation, with evidence implicating the downregulation of substance P and acid- sensing ion channel 1a (ASIC1a) in peripheral antinociception.16 Clinical studies have demonstrated that hydrodissection with 5–10 mL of 5% or 10% dextrose provides superior pain relief and functional improvement compared to normal saline or corticosteroid injectates, with durable benefits and a favorable safety profile.14,17

One of the most relevant clinical studies evaluating hydrodissection with dextrose for pain management in myofascial pain syndrome is the retrospective observational study by Wu et al.14 In this study, ultrasound-guided interfascial hydrodissection with 10% dextrose solution was administered to patients with refractory myofascial pain syndrome who had not responded to conventional treatments. Pain intensity was measured using the Numerical Rating Scale (NRS) at rest, nocturnally, and during exercise, with assessments at baseline, 4 weeks, and 12 weeks after the final injection. The findings demonstrated a statistically significant reduction in pain scores across all measured conditions at both 4- and 12-weeks post-treatment compared to baseline. This was measured through an instrument known as The EuroQol 5 Dimensions 5 Levels (EQ-5D-5L): a widely used, generic, patient-reported outcome measure designed to assess health-related quality of life (HRQoL) across diverse populations and disease states. It consists of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Additionally, the EQ-5D-5L instrument revealed significant improvements in the domains of pain/discomfort and anxiety/depression, while no significant changes were observed in mobility, self-care, or usual activities. Importantly, no serious adverse effects were reported, supporting the safety profile of the intervention. This study provides evidence that ultrasound- guided hydrodissection with 10% dextrose can yield meaningful and sustained pain relief, as well as improvements in psychological well-being, for patients with myofascial pain syndrome unresponsive to standard therapies.14

Hydrodissection with 5% dextrose has also been evaluated as a treatment for patients with persistent or recurrent carpal tunnel syndrome (CTS) following failed primary surgery. In a retrospective study, 61.1% of patients reported at least 50% symptom relief after a mean of 3.1 ultrasound-guided hydrodissection sessions, with a mean follow-up of 33 months. The procedure involved injection of 10 mL of 5% dextrose around the median nerve. Patients with recurrent symptoms after surgery were more likely to achieve an excellent outcome (defined as >70% improvement) compared to those with persistent symptoms (61.6% vs. 13%, p = 0.006). The durability of benefit was supported by similar rates of effective outcomes across different follow- up durations, up to more than four years post-treatment.18

Comparative studies of other injectates, such as normal saline or conventional active drug mixtures, suggest that the mechanical effect of hydrodissection itself is important, as both saline and active drug mixtures can reduce pain, but dextrose appears to offer additional benefit in some settings. For example, in peripheral nerve entrapment syndromes, systematic reviews have found that 5% dextrose hydrodissection is at least as effective, and sometimes superior, to corticosteroids or saline for pain relief and functional improvement, with a favorable safety profile.19 There is also evidence for hydrodissection with saline in treatment of refractory diabetic neuropathy.20 It stands to reason that if treatment with normal saline has promising results, that the results with dextrose would be even better. However, for myofascial pain syndrome specifically, the evidence base is still developing, and high-quality head-to-head trials comparing dextrose hydrodissection to other injectates (such as local anesthetics or corticosteroids) remain limited.

Summary and Cutting Edge Issues

Dextrose injection therapies have emerged as a significant area of interest in the management of musculoskeletal and neuropathic pain, with three principal modalities: prolotherapy (hypertonic dextrose with purported multifactorial mechanism), perineural injection therapy (5% dextrose for neuropathic pain), and hydrodissection (5–10% dextrose to mechanically release nerve entrapment). Prolotherapy involves injecting high-concentration dextrose (typically 12.5–25%) into ligaments, tendons, or joints to stimulate a local inflammatory response and promote tissue healing. Perineural injection therapy uses lower concentrations (5%) adjacent to peripheral nerves and may modulate neurogenic inflammation and pain signaling, while hydrodissection employs 5–10% dextrose under ultrasound guidance to mechanically separate nerves from surrounding tissues, providing both decompressive and biochemical relief. These modalities are increasingly adopted for conditions such as carpal tunnel syndrome, myofascial pain, and various entrapment neuropathies, reflecting a growing evidence base and clinical interest.

Recent studies and meta-analyses demonstrate that 5% dextrose injections are effective for peripheral entrapment neuropathies, with significant improvements in pain and function compared to saline and corticosteroids, particularly in carpal tunnel syndrome. Hydrodissection with dextrose has shown efficacy and safety in refractory myofascial pain and post-surgical nerve entrapment, with durable benefits and minimal adverse effects. Prolotherapy, while promising for osteoarthritis and chronic soft tissue injuries, shows mixed results that are often condition-specific; it may outperform corticosteroids in certain domains (e.g., sacroiliac joint pain), but large high-quality effectiveness studies have yet to be done. Across modalities, dextrose injections are associated with a favorable safety profile, with fewer adverse effects than corticosteroids, especially in the context of carpal tunnel syndrome. Current research is also looking into laser therapy and ozone therapies as pain management techniques.21,22 These areas require further research as current studies are limited to pain secondary to osteoarthritis in knees.

Limitations in the optimization of dextrose injections include the lack of standardized protocols for dextrose concentration, dosing, and injection technique, as well as heterogeneity in study designs and limited high-quality, long-term trials. Mechanistic research is ongoing, with recent work suggesting pathways such as substance P and acid-sensing ion channel 1a (ASIC1a) in dextrose-mediated analgesia. There is a need for head-to-head trials comparing dextrose with other injectates, and for studies that define optimal patient selection and procedural parameters. The increasing use of ultrasound guidance is refining procedural accuracy and safety, but further research is required to establish best practices. As dextrose therapies continue to fill gaps in non-surgical pain management, rigorous studies are needed to inform clinical guidelines and optimize outcomes.

Gaps in Knowledge

The most significant gaps in knowledge regarding dextrose injection therapies relate to the lack of standardization in treatment protocols and insufficient high-quality, long-term comparative studies. There is considerable heterogeneity in the concentration of dextrose used, injection volume, frequency, anatomical targets, and technique, making it difficult to compare outcomes across studies or to establish optimal regimens for specific conditions. For example, studies in plantar fasciopathy and lateral epicondylitis use varying dextrose concentrations and injection schedules, and meta-analyses consistently call for larger, rigorously designed randomized controlled trials with standardized protocols and longer follow-up to clarify efficacy and durability of benefit. Additionally, the majority of available evidence is limited to short- or medium-term outcomes, with few studies extending beyond six months, and many trials are underpowered to detect rare adverse events or to compare dextrose directly with other active injectates such as corticosteroids or platelet-rich plasma.

Mechanistic understanding of dextrose’s analgesic and regenerative effects remains incomplete, and the clinical relevance of proposed biological pathways is not fully established. While preclinical data suggest roles for substance P and acid-sensing ion channel 1a (ASIC1a) in mediating dextrose-induced analgesia, these findings have not yet been translated into robust clinical biomarkers or predictors of response. Furthermore, there is a lack of clarity about which patient characteristics predict likelihood and degree of benefit, the ideal injection protocol and dosing, and the comparative effectiveness of dextrose versus other injectates for different musculoskeletal and neuropathic pain syndromes. As a result, current clinical recommendations are limited by low to moderate certainty of evidence. Dextrose based injection therapy may be an option for carefully selected patients who have failed other more conventional non-surgical care. Further high-quality research is needed to address these limitations.

References

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  22. Farpour HR, Ashraf A, Hosseini SS. The Efficacy of Ozone Prolotherapy Compared to Intra-Articular Hypertonic Saline Injection in Reducing Pain and Improving the Function of Patients with Knee Osteoarthritis: A Randomized Clinical Trial. Evid Based Complement Alternat Med. 2021;2021:5579944. Published 2021 Aug 3. doi:10.1155/2021/5579944

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

Previous Revision(s) of the Topic

Mooyeon Oh-Park, MD, Emma Desjardins, DO, Areeb Chator, MD, Lili Wang, DO, Dean Reeves, MD. Therapeutic Injection of Dextrose: Prolotherapy, Perineural Injection Therapy and Hydrodissection. 1/18/2023

Author Disclosure

Chaitanya Konda, DO
Nothing to Disclose

Ammar Khan, MD
Nothing to Disclose

Victoria Noel, MD
Nothing to Disclose

Dean Reeves, MD
Nothing to Disclose

David Rabago, MD
Nothing to Disclose