OBJECTIVEThe aim of this study was to systematically review dextrose (d-glucose) prolotherapy efficacy in the treatment of chronic musculoskeletal pain.DATA SOURCESElectronic databases PubMed, Healthline, OmniMedicalSearch, Medscape, and EMBASE were searched from 1990 to January 2016.STUDY SELECTIONProspectively designed studies that used dextrose as the sole active prolotherapy constituent were selected.DATA EXTRACTIONTwo 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 SYNTHESISFourteen 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.CONCLUSIONUse 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.

Ligament injuries are among the most common causes of musculoskeletal joint pain and disability encountered in primary practice today. Ligament injures create disruptions in the balance between joint mobility and joint stability, causing abnormal force transmission through the joint, which results in damage to other structures in and around the joint. The long-term consequence of nonhealed ligament injury is osteoarthritis, the most common joint disorder in the world today.Ligaments heal through a distinct sequence of cellular events that take place in three consecutive stages: an acute inflammatory phase, a proliferative or regenerative phase, and a tissue remodeling phase. The process can take months to resolve itself, and despite advances in therapeutics, many ligaments do not regain their normal tensile strength.Various diagnostic procedures have been used to determine and assess ligament injury. Traditionally, MRI and X-rays have been the most utilized techniques; however, because ligaments do not show up clearly with these devices, there have been many false positives and negatives reported due to inconclusive or inaccurate readings. Newer technologies, such as ultrasound and digital motion X-ray, are able to provide a more detailed image of a ligament's structure and function.Numerous strategies have been employed over the years attempting to improve ligament healing after injury or surgery. One of the most important of these is based on the understanding that monitoring early resumption of activity can stimulate repair and restoration of function and that prolonging rest may actually delay recovery and adversely affect the tissue's response to repair. Likewise, there is a shift away from the use of steroid injections and nonsteroidal antiinflammatory medications. Although these compounds have been shown effective in decreasing the inflammation and pain of ligament injuries for up to six to eight weeks, their use has been shown to inhibit the histological, biochemical, and biomechanical properties of ligament healing. For this reason their use is cautioned against in athletes who have ligament injuries. Such products are no longer recommended for chronic soft tissue injuries or for acute ligament injuries, except for the shortest possible time, if at all.Regenerative medicine techniques, such as prolotherapy, have been shown, in both case series and clinical studies, to resolve ligament injuries of the spine and peripheral joints. More research and additional studies are needed to better assess ligament injuries and healing properties.

The use of conventional modalities for chronic neck pain remains debatable, primarily because most treatments have had limited success. We conducted a review of the literature published up to December 2013 on the diagnostic and treatment modalities of disorders related to chronic neck pain and concluded that, despite providing temporary relief of symptoms, these treatments do not address the specific problems of healing and are not likely to offer long-term cures. The objectives of this narrative review are to provide an overview of chronic neck pain as it relates to cervical instability, to describe the anatomical features of the cervical spine and the impact of capsular ligament laxity, to discuss the disorders causing chronic neck pain and their current treatments, and lastly, to present prolotherapy as a viable treatment option that heals injured ligaments, restores stability to the spine, and resolves chronic neck pain.The capsular ligaments are the main stabilizing structures of the facet joints in the cervical spine and have been implicated as a major source of chronic neck pain. Chronic neck pain often reflects a state of instability in the cervical spine and is a symptom common to a number of conditions described herein, including disc herniation, cervical spondylosis, whiplash injury and whiplash associated disorder, postconcussion syndrome, vertebrobasilar insufficiency, and Barré-Liéou syndrome.When the capsular ligaments are injured, they become elongated and exhibit laxity, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches. In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain. In either case, the presence of excessive motion between two adjacent cervical vertebrae and these associated symptoms is described as cervical instability.Therefore, we propose that in many cases of chronic neck pain, the cause may be underlying joint instability due to capsular ligament laxity. Currently, curative treatment options for this type of cervical instability are inconclusive and inadequate. Based on clinical studies and experience with patients who have visited our chronic pain clinic with complaints of chronic neck pain, we contend that prolotherapy offers a potentially curative treatment option for chronic neck pain related to capsular ligament laxity and underlying cervical instability.

Regenerative therapeutic strategies for joint diseases usually employ either enriched concentrates of bone marrow-derived stem cells, chondrogenic preparations such as platelet-rich plasma, or irritant solutions such as hyperosmotic dextrose. In this case series, we describe our experience with a simple, cost-effective regenerative treatment using direct injection of unfractionated whole bone marrow (WBM) into osteoarthritic joints in combination with hyperosmotic dextrose. Seven patients with hip, knee or ankle osteoarthritis (OA) received two to seven treatments over a period of two to twelve months. Patient-reported assessments were collected in interviews and by questionnaire. All patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress under other therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise. These preliminary findings suggest that OA treatment with WBM injection merits further investigation.

We retrospectively evaluated the effectiveness of prolotherapy in resolving pain, stiffness, and crepitus, and improving physical activity in consecutive chondromalacia patients from February 2008 to September 2009. Sixty-nine knees that received prolotherapy in 61 patients (33 female and 36 male) who were 18–82 years old (average, 47.2 years) were enrolled. Patients received 24 prolotherapy injections (15% dextrose, 0.1% procaine, and 10% sarapin) with a total of 40 cc in the anterior knee. At least 6 weeks after their last prolotherapy session, patients provided self-evaluation of knee pain upon rest, activities of daily living (ADL) and exercise, range of motion (ROM), stiffness, and crepitus. Symptom severity, sustained improvement of symptoms, number of pain pills needed, and patient satisfaction before treatment and improvement after treatment were recorded. Following prolotherapy, patients experienced statistically significant decreases in pain at rest, during ADL, and exercise. Stiffness and crepitus decreased after prolotherapy, and ROM increased. Patients reported improved walking ability and exercise ability after prolotherapy. For daily pain level, ROM, daily stiffness, crepitus, and walking and exercise ability, sustained improvement of over 75% was reported by 85% of patients. Fewer patients required pain medication. No side effects of prolotherapy were noted. The average length of time from last prolotherapy session was 14.7 months (range, 6 months to 8 years). Only 3 of 16 knees were still recommended for surgery after prolotherapy. Prolotherapy ameliorates chondromalacia patella symptoms and improves physical ability. Patients experience long-term improvement without requiring pain medications. Prolotherapy should be considered a first-line, conservative therapy for chondromalacia patella.

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Joint dysfunctions and associated musculoskeletal pain are among the most common medical complaints presented to clinicians. Ligaments are collagenous fibrous structures that are primarily responsible for maintaining smooth joint motion, restraining excessive joint displacement, and providing stability across the joint. Ligaments also act as sensory organs for the joints and have significant input to pain sensation. When ligaments are subjected to forces beyond their normal range of motion, injury and failure occur, resulting in joint laxity (looseness or instability), and subsequent disruptions in the balance between joint mobility and joint stability. These dysfunctions can result in joint pain and the development of osteoarthritis. Several strategies have been employed over the years in attempts to improve joint instability from ligament injury; however, some of the standard therapeutic approaches (drugs, corticosteroid injections, and surgery) employed to address these problems have not been very effective because they often do not address the underlying cause of the problems, and in fact can inhibit ligament healing and restoration. For these reasons, there is current and growing interest among patients and clinicians in prolotherapy, an alternative therapeutic modality that can reduce or eliminate pain by stimulating the natural regenerative processes in and around the joint to facilitate the restoration of degenerated ligaments and tendons to a healthy state, improving joint support, function and reducing pain. This review presents current evidence from clinical studies demonstrating that prolotherapy is a significant and effective alternative treatment modality for people with ligament-related injuries and resultant joint instability.

Adult mesenchymal stem cells (MSCs) obtainable from autologous bone marrow aspirates have generated tremendous interest in the medical and scientific communities in the last two decades and are currently being investigated by a of interested physicians for use in point-of-care stem cell therapies due to their great potential to differentiate into multiple cell lineages such as bone, cartilage, muscle, tendon, and nerve. However, as these stem cells are found in very low numbers in adult tissue, centrifugal concentration or expansion through in vitro culturing has been pursued to obtain higher numbers of efficacious regenerative therapeutic applications. More recently, some physicians and scientists have chosen to explore use for direct injection of un-fractionated, native whole bone marrow aspirate as a strategy in regenerative treatment regimes. This review examines the potential merits and disadvantages of using either concentrated and culture expanded MSCs versus native whole bone marrow aspirate as key proliferant in direct regenerative injection therapy (RIT). Results from a number of published investigations have clearly shown high potential of various deleterious effects on manipulating MSCs obtained from native bone marrow aspirate either by centrifugal forces or expansion through in vitro culturing; moreover, currently used centrifugal concentration techniques do not significantly concentrate MSCs from bone marrow aspirate, thus, defeating the purpose of this manipulative step. On the other hand, preliminary results and observations of using un-fractionated whole bone marrow injection for treatment of various musculoskeletal joint diseases (for example, osteoarthritic joints) suggest that the procedure is safe and potentially efficacious, with no known deleterious effects as yet reported.