Local 5% dextrose-based therapies as tissue-level metabolic modulators: a unifying hypothesis for their biological effects
Medical Hypotheses, cilt.215, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 215
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.mehy.2026.112109
- Dergi Adı: Medical Hypotheses
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE
- Anahtar Kelimeler: Dextrose injection, prolotherapy, insulin resistance, hydrodissection, perineural injection therapy, glucose metabolism
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Dextrose-based therapies, including prolotherapy, perineural injection therapy, hydrodissection, and ultrasound-guided 5% dextrose injections, have gained increasing acceptance in the management of musculoskeletal pain and peripheral nerve disorders. Although numerous clinical studies have reported beneficial outcomes, the biological mechanisms underlying these effects remain incompletely understood. Current explanations emphasize modulation of neurogenic inflammation, transient receptor potential vanilloid-1 (TRPV1) signaling, mechanical separation of tissue planes, and stimulation of tissue repair. However, these mechanisms do not fully explain why local administration of the same low-concentration dextrose solution appears beneficial across a broad spectrum of musculoskeletal and neural disorders. I propose a novel hypothesis that local 5% dextrose functions as a tissue-level metabolic modulator capable of transiently activating nutrient-sensitive metabolic signaling pathways in metabolically stressed tissues. Rather than acting solely as an energy substrate, transient local glucose exposure may enhance glucose bioavailability, activate nutrient-sensing pathways, and initiate downstream signaling mechanisms involved in inflammation, neuromodulation, and tissue repair. Age-related insulin resistance is proposed as one clinically relevant contributor to tissue metabolic vulnerability, together with local inflammation, chronic mechanical stress, and microvascular dysfunction, all of which may impair effective cellular glucose utilization despite adequate systemic glucose availability. This hypothesis provides a unifying biological framework linking the clinical success of multiple dextrose-based therapies. It predicts that treatment response may correlate with markers of metabolic dysfunction and that local dextrose administration may induce measurable changes in cellular metabolic signaling pathways. Experimental and clinical studies evaluating tissue glucose utilization, metabolic signaling, and molecular responses before and after 5% dextrose injection may help validate or refute this concept. If confirmed, local 5% dextrose-based therapy may represent a previously underrecognized form of targeted tissue metabolic modulation.