More and more clinicians have interesting experiences with glucose 5% injections. However, we lack fundamental research to support our clinical findings. (below: more information about Glucopuncture / glucose 5% injections)

Jan Kersschot

Glucopuncture: Introduction

1. Definition

Glucopuncture is a nonsteroidal injection therapy for the management of a variety of nonrheumatic musculoskeletal conditions. It consists of series of sessions of multiple regional glucose 5% injections into the dermis and into muscles, tendons, and ligaments. Intradermal injections are given to modulate referred pain and intralesional injections are applied to support tissue repair.

2. History

Glucose and dextrose injections have been used for several decades in prolotherapy ([i], [ii], [iii], [iv], [v], [vi], [vii], [viii], [ix]). Hypertonic dextrose prolotherapy typically uses high concentrations of dextrose (10% net concentration or more). Such hyperosmolar solutions lead to localized cell destruction. This phenomenon creates a local inflammatory reaction. This may lead to tissue proliferation – hence the description prolotherapy - and even formation of scar tissue.

Over the last decade, low concentrations of glucose 5% (or dextrose 5%) have become more popular ([x], [xi], [xii], [xiii], [xiv], [xv], [xvi], [xvii]). Clinical experience indicates that glucose 5% injections may be effective for the management of a variety of musculoskeletal conditions. Despite interesting clinical outcome, glucose 5% injections have not received much attention among family physicians, sports doctors, or orthopaedic surgeons. The term Glucopuncture (GP) was introduced in January 2021 to change that situation ([xviii]).

3. Mechanism of Action

3. 1. Pain Modulation and Tissue Repair

Most hypotheses about glucose injections are focused on pain modulation (e.g., vanilloid receptors, neural inflammation, gate control). But these theories on pain modulation are not specific for glucose injections. Furthermore, these theories do not explain the beneficial effects of Glucopuncture on tissue repair. Certain tissues seem to function better after a few sessions. Apparently, local glucose injections support cellular function and consequently lead to tissue repair clinical functional improvement. This functional improvement leads to, for example, less stiffness when injecting into muscle, and more joint stability when injecting into collateral bands or ligaments. To explain this functional component, a new hypothesis has been proposed, the ATP hypothesis.

3.2. The ATP Hypothesis

Glucose is the major energy source for cellular health. One glucose molecule gives rise to more than 30 ATP molecules during the aerobic respiration. The conversion of ATP into ADP releases about 30 kJ/mol energy to the cells. In other words, glucose can be considered as a direct provider of energy (one molecule delivers more than 900 kJ/mol) to cell metabolism.

When tissues are damaged because of trauma, overuse or other causes, the cells need to regenerate as quickly as possible. This physiological tissue regeneration requires an additional amount of energy in the cells. In normal circumstances, energy supply is abundant to meet the higher demand. The cells are so to speak self-sufficient when it comes to ATP production. But when the need for ATP is elevated, there may be a temporary lack of ATP and as a result physiological recovery of that tissue may become impossible. The latter may lead to poor tissue healing. Providing extra glucose to the cells during these moments of repair might lead to extra ATP production. In this sense, it is hypothesized that Glucopuncture improves tissue repair of, for example, muscles, tendons, and ligaments.

3.3. The Effect of Glucose on Tiny Nerve Branches

Especially peripheral nerve endings seem to respond well to adjacent glucose injections. This effect is not observed when glucose is injected intravenously, which may mean that the mechanism of action is located in the extracellular matrix at the injection site. More research is required to further explore this. One can approach the peripheral nerves directly, for example, when injecting close to the median nerve (carpal tunnel) or greater occipital nerve. But clinical experience has illustrated that it is not always necessary to inject adjacent to peripheral nerves. Reaching the finer branches with glucose seems to be equally important. These extremely tiny nerve endings are present in muscles, tendons, ligaments, and so on. These fine nerve branches are also impossible to find during clinical examination – let alone inject each one of them separately. That is why multiple injections are given in the entire region.

3.4. The Effect of Glucose on Dermal Sensory Nociceptors

Sensory receptors are found everywhere in the body. They are also abundant in dermis. That is probably the reason why superficial injections of glucose can be more influential than expected. It is sometimes said that the skin is the largest sensory organ of the human body. These dermal sensory receptors are an important part of the somatosensory system. These receptors include mechanoreceptors, nociceptors, and thermoreceptors. Especially dermal nociceptors are important to explain the pain modulating effects of Glucopuncture while injecting glucose intradermally.

In other words, it is hypothesized that peripheral nerves which are irritated or inflamed, require more glucose than normally because they are mechanically irritated, inflamed or both. At some point, the ATP levels are too low and ‘batteries’ are empty. Providing additional ATP through glucose injection might resolve this issue temporary. This so-called ‘charging’ of the cells must be repeated on a regular basis until the cells can continue to function without external sources of ATP. That might explain why it is crucial to repeat the Glucopuncture sessions on a regular basis, especially in the beginning of treatment. This theory is still hypothetical and more research in this field is required to confirm these statements.

3.5. Glucose transport across the cell membrane

Glucose is transported across the cell membrane ([xix]) by a specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient.

The understanding of glucose transport after extracellular injection and its consequent effect on small branches of peripheral nerve endings in, for example, muscle tissue, tendons, ligaments, and its effect on dermal nociceptors is obviously still incomplete and needs further investigation. It is hoped that the introduction of Glucopuncture and its promising clinical effects might stimulate more research in the field of neural inflammation and the beneficial effects of regional glucose injections. Unfortunately, glucose is an inexpensive product which cannot be patented, so it is very unlikely to receive funding for large randomized clinical trials from pharmaceutical companies.

see also: www.glucopuncture.com

[i] Reeves KD, Sit RW, Rabago DP. Dextrose Prolotherapy: A Narrative Review of Basic Science, Clinical Research, and Best Treatment Recommendations. Phys Med Rehabil Clin N Am. 2016 Nov;27(4):783-823. doi: 10.1016/j.pmr.2016.06.001. PMID: 27788902

[ii] Distel LM, Best TM. Prolotherapy: a clinical review of its role in treating chronic musculoskeletal pain. PM R. 2011 Jun;3(6 Suppl 1):S78-81. doi: 10.1016/j.pmrj.2011.04.003. PMID: 21703585.

[iii] Ganji R. Dextrose prolotherapy for improvement of rotator cuff lesions: ready for clinical use?. Hong Kong Med J. 2018;24(4):429–430. doi:10.12809/hkmj187480

[iv] Rabago D, Nourani B. Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review. Curr Rheumatol Rep. 2017 Jun;19(6):34. doi: 10.1007/s11926-017-0659-3. PMID: 28484944.

[v] Rabago D, Kansariwala I, Marshall D, Nourani B, Stiffler-Joachim M, Heiderscheit B. Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis: Feasibility, Acceptability, and Patient-Oriented Outcomes in a Pilot-Level Quality Improvement Project. J Altern Complement Med. 2019;25(4):406–412. doi:10.1089/acm.2018.0361

[vi] Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med. 2003 May-Jun;9(3):58-62. PMID: 12776476.

[vii] Dwivedi S, Sobel AD, DaSilva MF, Akelman E. Utility of Prolotherapy for Upper Extremity Pathology. J Hand Surg Am. 2019 Mar;44(3):236-239. doi: 10.1016/j.jhsa.2018.05.021. Epub 2018 Jun 23. PMID: 29945842.

[viii] Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000 Mar;6(2):68-74, 77-80. PMID: 10710805

[ix] Seven MM, Ersen O, Akpancar S, Ozkan H, Turkkan S, Yıldız Y, Koca K. Effectiveness of prolotherapy in the treatment of chronic rotator cuff lesions. Orthop Traumatol Surg Res. 2017 May;103(3):427-433. doi: 10.1016/j.otsr.2017.01.003. Epub 2017 Feb 16. PMID: 28215611.

[x] Maniquis-Smigel L, Reeves KD, Rosen JH, et al. . Short term analgesic effects of 5% dextrose epidural injection for chronic low back pain. A randomized controlled trial. Anesth Pain Med 2017;7:e42550.

[xi] Köroğlu, Özlem & Orscelik, Aydan & Karasimav, Özlem & Demir, Yasin & Solmaz, İlker. (2019). Is 5% dextrose prolotherapy effective for radicular low back pain? Gulhane Medical Journal . 2019, Vol. 61 Issue 3, p123-127. 5p.

[xii] Lyftogt, John. (2007). Subcutaneous prolotherapy treatment of refractory knee, shoulder, and lateral elbow pain. Australasian Musculoskel Med. 12. 107-109.

[xiii] Weglein, AD. Neural Prolotherapy. Journal of Prolotherapy. 2001;3(2):639-643

[xiv] Paprottka KJ, Lehner A, Fendler WP, et al. Reduced periprocedural analgesia after replacement of water for injection with glucose 5% solution as the infusion medium for 90Y-Resin microspheres. J Nucl Med. 2016;57(11)(1679-1684).

[xv] Mansız-Kaplan B, Nacır B, Pervane-Vural S, Genç H. Pain relief in a patient with snapping scapula after 5% dextrose injection. Turk J Phys Med Rehabil. 2020 Aug 18;66(3):368-369. doi: 10.5606/tftrd.2020.4169. PMID: 33089095; PMCID: PMC7557628.

[xvi] Solmaz İ, Akpancar S, Örsçelik A, Yener-Karasimav Ö, Gül D. Dextrose injections for failed back surgery syndrome: a consecutive case series. Eur Spine J. 2019 Jul;28(7):1610-1617. doi: 10.1007/s00586-019-06011-3. Epub 2019 May 21. PMID: 31115685

[xvii] Amanollahi, A., Asheghan, M., & Hashemi, S. E. (2020). Subacromial corticosteroid injection versus subcutaneous 5% dextrose in patients with chronic rotator cuff tendinopathy: A short-term randomized clinical trial, Interventional Medicine and Applied Science IMAS, 11(3), 154-160

[xviii] Kersschot J, Glucopuncture: Series of Regional Multiple Glucose 5% Injections. Adv Complement Alt Med. 6(2). ACAM.000636.2021.

[xix] Jurcovicova J. Glucose transport in brain - effect of inflammation. Endocr Regul. 2014 Jan;48(1):35-48. doi: 10.4149/endo_2014_01_35. PMID: 24524374.