Prolotherapy: Potential for the Treatment of Chronic Wounds?

Abstract

Significance: Chronic skin ulcers, including venous, diabetic, and pressure ulcers, constitute a major health care burden, affecting 2-6 million people in the United States alone, with projected increases in incidence owing to the aging population and rising epidemic of diabetes. The ulcers are often accompanied by pain. Standard of care fails to heal *50% of diabetic foot ulcers and 25% of venous leg ulcers. Even advanced therapies do not heal >60%. Thus there is an unmet need for novel therapies that promote healing and also address the concomitant pain issue. Recent Advances: Prolotherapy involves injection of small amounts of an irritant material to the site of degenerated or painful joints, ligaments, and tendons. Multiple irritants are reported to be efficacious, but the focus here is on dextrose prolotherapy. In vitro and in vivo studies support translation to clinical use. Concentrations as low as 5% dextrose have resulted in production of growth factors that have critical roles in repair. Numerous clinical trials report pro-reparative effects of dextrose prolotherapy in joint diseases, tendon, and ligament damage, and for painful musculoskeletal issues. However, most of the studies have limitations that result in low-quality evidence. Critical Issues: The preclinical data support a role for dextrose prolotherapy in promoting tissue repair that is required for healing chronic wounds and ameliorating the associated pain. Critical issues include provision of evidence of efficacy in human chronic wounds. Another potential obstacle is limitation of reimbursement by third-party payers for a therapy with as yet limited evidence. Future Directions: Preclinical studies in models of chronic wounds would support clinical translation. As dextrose prolotherapy has some mechanistic similarities to already approved honey therapies, it may have a shortened pathway for clinical translation. The gold standard for widespread adoption would be a well-designed clinical trial.

Enhanced Wound Healing With Caloric Restriction, Refeeding, And Intermittent Fasting: Dietary Strategies In Support Of Bioproliferative Injection Therapies

“…Dextrose prolotherapy may also promote tissue repair that is required for healing chronic wounds and ameliorating the associated pain. 50 There also appears to be some benefit with short term if, crrf, kds in support of prolotherapy treatment. However caution is required, as even short term carbohydrate restriction has some potential complications such as transient hunger, headache, constipation, low mood fatigue, irritability and loss of concentration with these symptoms particularly affecting the obese.…”

Strategies and challenges in the treatment of chronic venous leg ulcers

“…Preclinical data support a role for dextrose prolotherapy in promoting tissue repair that is required for healing chronic wounds and ameliorating the associated pain. Five percent dextrose can cause the production of growth factors that have critical roles in repair[ 4 ]. Furthermore, numerous clinical trials report pro-reparative effects of dextrose prolotherapy in joint diseases, tendon and ligament damage, and painful musculoskeletal issues[ 4 ].…”

Acupoint Injection of Dextrose Attenuates Chronic Inflammatory Pain In Mice Through Modulation of Transient Receptor Potential V1 Channel Expression

“…Although prolotherapy has demonstrated e cacy for healing local tissue damage, the underlying mechanisms of action are still unclear. One possibility is that dextrose induces osmotic damage to local neurons, which in turn attracts brain-resident in ammatory mediators to initiate the wound-healing cascade [5]. Local osmotic damage may also induce the in ltration of granulocytes followed by monocytes and macrophages [6].…”