I. NEUropATHIC PAIN

Nerves are usually viewed as simple conduits of electrical signals to make muscles move and enable sensation of pain, temperature and pressure. However, axons within nerves, also known as nervi nervorum, are also capable of reacting to their immediate environment, such as to mechanical pressure or to direct injury from trauma.

Nociceptors are sensory neurons that detect harmful stimuli, and can become sensitized after infection (e.g., herpes), direct injury, surgery [i,ii] or repetitive overstimulation. When nociceptors are sensitized, they often exhibit spontaneous activity in the absence of stimulation, called "ongoing activity" [iii]. Because of their very specialized anatomy and physiology, nerves are capable of creating or mediating certain types of (chronic) pain [iv]. It has been made clear that nociceptor neurons also release neuropeptides and neurotransmitters from nerve terminals which can regulate adaptive immune cell responses [v]. Macrophages can activate nociceptors and nociceptors can secrete neuropeptides and chemokines which act on macrophages; in chronic pain these bilateral macrophage-nociceptor interactions are mediated by microRNAs and microRNA-containing exosomes [vi].

Neuropathic pain (NP) is described as a (superficial) pain arising as a direct consequence of a lesion or disease affecting the somatosensory system at the peripheral or central level [vii]. It affects about $10\mathrm{\%}$ of the world population [viii, ix]. Despite the progress in pain management methods made over the last decades, neuropathic pain significantly impacts patients' quality of life. Both pharmacological and nonpharmacological methods often fail to reduce the pain or may induce serious side effects. Neuropathic pain resulting from diabetes or chemotherapy are not considered as a subject of this article.

Diverse causes of neuropathic pain are associated with excessive inflammation in both the peripheral and central nervous system which may contribute to the initiation and even maintenance of persistent pain [x]. Chemical mediators, such as cytokines, released during an inflammatory response have the undesired side effect of sensitizing or stimulating nociceptors. These changes can promote long-term persistent neuropathic pain. Transient receptor potential vanilloid channel 1 (TRPV1), a nonselective cation channel, has been shown to play an important role in neuropathic pain (xi). It has been found that IL-6 and IL-1beta also play a role in pain induced by perineural inflammation [xii]. All this may explain why sometimes a minor trauma can lead to extreme sensitivity to touch (allodynia) and severe chronic neuropathic pain.

II. LOCALIZED NEUropATHIC PAIN

In more than half of cases of NP, the pain is localized and affects a certain area of the body [xiii]. This article focuseses on this peripheral or localized type of neuropathic pain. Localized neuropathic pain (LNP) is characterized by circumscribed areas of pain with abnormal skin sensitivity or spontaneous burning pain with no obvious cause.

It is hypothesized that even a minor peripheral nerve injury can induce functional and structural changes in neuronal cells. These functional and structural changes release numerous signaling molecules in response to the nerve damage. As these mediators modulate corresponding receptors on cell membranes, such interactions can create vicious circles of complaints such as burning pain and allodynia. These maladaptive mechanisms contribute to further sensitization of peripheral nerve endings [xiv]. It is hypothesized that noxious stimuli stimulate peripheral nerves to release calcitonin gene-related peptide

(CGRP) and prostaglandin E2 (PGE2) [xv]. Interleukin-1beta also seems to play a role in neuropathic pain [xvi, xvii].

III. DIFFERENTIAL DIAGNOSIS

LNP needs to be differentiated from complex regional pain syndrome (CRPS) which is a difficult-to-treat chronic pain condition [xviii]. CRPS often involves hyperalgesia and allodynia of the extremities and on top of that there is autonomic nervous system involvement. CRPS is not an indication for Glucopuncture. Neither can neuropathic pain resulting from nerve compression, autoimmune disease, diabetes [xiv] or chemotherapy be treated with Glucopuncture.

IV. REGIONAL TREATMENTS FOR LOCALIZED NEUropATHIC PAIN

The standard treatment of LNP is antidepressants and anticonvulsants [xx]. Regional treatments such as patches and injections are gaining popularity in the local management of peripheral neuropathic pain. A major advantage of transdermal treatments is that they may reduce the risk of adverse events that are often associated with systemic medication. Topical modalities may be used in combination with oral drugs resulting in less drug-drug interactions.

Topical treatments such as $5\mathrm{\%}$ lidocaine patches and $8\mathrm{\%}$ capsaicin patches have been used in several LNP models [xxi, xxii, xxiii]. In this article, the focus will solely be on local intradermal injections with glucose $5\mathrm{\%}$. Typically, $1\mathrm{mL}$ of solution is injected per cm (half inch) of the symptomatic area. Positive feedback of patients treated with this new technique has encouraged certain clinicians to present it as a new approach to treat mild forms of LNP. The new term Glucopuncture is introduced to raise awareness about these injections among both doctors and patients. However, no randomized clinical trials have illustrated its safety or efficacy yet. This technique is especially interesting for physicians who work in remote areas where modern diagnostic and therapeutic modalities are not available, or too expensive for their patients.

V. GLUCOPUNCTURE FOR MILD LOCALIZED NEUropATHIC PAIN

As pointed out earlier, first-line pharmacological treatments for LNP include pain medication, antidepressants and anticonvulsants such as gabapentin and pregabalin [xxiv]. However, some patients complain about side effects of such medication. Others obviously overuse pain medication. One of the goals of Glucopuncture is to reduce the use of systemic medication by giving a series of glucose $5\mathrm{\%}$ injections intradermally. Best results are achieved when the injections are started in the beginning of the disease before the somatosensory system is affected at central level. Instead of giving intradermal injections, one can also give the glucose perineurally [xxv, xxvi, xxvii] but this technique is not a topic of this article. Clinical randomized studies are required to see which dose, frequency and injection technique works best for mild LNP.

VI. DEFINITION OF GLUCOPUNCTURE

Glucopuncture (GP) is an easy-to-learn procedure which can be done in a small private practice without ultrasound guidance. GP is defined as an injection-based therapy for the management of a variety of musculoskeletal conditions [xxviii]. In general, glucose $5\mathrm{\%}$ in water (G5W) injections are given in dermis, muscles, fascia, tendons and ligaments. No local anesthetics nor corticosteroids are added. When treating localized neuropathic pain, multiple intracutaneous injections with G5W in the zone of pain referral are advised. The treatment is repeated once a week to once every two weeks. After a series of sessions, the pain modulation can last up to several months. If no major improvement is noticed after five sessions, the treatment is stopped.

VII. GLUCOSE METABOLISM IN BRAIN CORTEX

The human brain depends upon glucose as its main source of energy, and glucose metabolism is critical for brain physiology [xxix, xxx]. The brain accounts for about $2\mathrm{\%}$ of the body weight, yet it consumes about $20\mathrm{\%}$ of glucose-derived energy [xxxi]. Glucose metabolism provides the fuel for physiological brain function through the generation of ATP, the foundation for neuronal and non-neuronal cellular maintenance [xxxii]. Therefore, regulation of glucose metabolism is critical for cortex physiology [xxxiii]. The largest proportion of energy in the brain is consumed for neuronal computation and information processing [xxxiv], e.g., the generation of action potentials and postsynaptic potentials generated after synaptic events, and the maintenance of ion gradients and neuronal resting potential [xxxv]. Additionally, glucose metabolism provides the energy and precursors for the biosynthesis of neurotransmitters [xxxvi]. The question is whether glucose is equally important for the peripheral nervous system as it is for the brain. This question has not been answered yet, but further exploration of this issue might explain the clinical effects which are noticed when injecting isotonic glucose perineurally (e.g., carpal tunnel) or intradermally. It is clear that when glucose is applied to a patient systemically, for example, as an IV infusion, there are no pain modulating effects at all. This means that in the search for the exact mode of action of Glucopuncture, the scientific community needs to focus on what exactly is happening when the glucose arrives directly in the extracellular matrix (ECM). In other words, the mechanisms of action of glucose as found in lab tests (in vitro) or hypotheses from diabetic research provide only limited value.

VIII. WORKING HYPOTHESIS OF GLUCOPUNCTURE

Glucose is a crucial energy source for cellular health. The goal of Glucopuncture is to deliver additional glucose in the extracellular space to support directly cellular ATP production. Hypertonic solutions are not advised because they lead to osmotic destruction of the cells. When glucose is injected into the body, it arrives in the extracellular matrix (ECM). Then, the glucose is transported across the cell membrane [xxxvii].

a) The Effect of Glucose on Dermal Sensory Nociceptors

Nociceptors are sensory neurons that detect harmful stimuli, and can become sensitized following injury or repetitive stimulation. When sensitized, nociceptors often exhibit spontaneous activity in the absence of apparent stimulation [xxxviii]. Sensory receptors are found in dermis, muscles, fascia, tendons and ligaments [xxix]. These receptors include mechanoreceptors, nociceptors, and thermoreceptors [xl, xli]. Especially dermal nociceptors [xlii, xliii, xliv] are important to explain the pain modulating effects of intradermal glucose injections. And this is very likely the most important mechanism when treating regional neuralgia [xlv]. The transient receptor potential ankyrin1 (TRPA1), a member of the TRP channels, acts as 'polymodal cellular sensor' on primary sensory neurons where it mediates the peripheral and central processing of pain [xlv].

b) ATP as a Pain Modulator

ATP may play a direct role in pain modulation, especially when dealing with peripheral nerves. It has been illustrated that ATP injection increases expression of several markers for regenerative activity in sensory neurons, including phospho-STAT3 and GAP43 [xlvii]. It has been found that ATP infusion improves spontaneous pain and tactile allodynia [xlviii, xlix] in patients with (postherpetic) neuralgia. It also became clear that it works for neuropathic orofacial pain, but not for other types of orofacial pain, indicating that the neuropathic element seems to be an important factor in the effects of ATP [I]. These studies might indicate that glucose may have its pain modulating effects on neuropathic pain via ATP [li]. More research in this field may confirm the anecdotal information available so far.

IX. HISTORY OF GLUCOPUNCTURE

Subcutaneous injections with glucose $5\mathrm{\%}$ were first described in the treatment of Achilles tendinopathy [lii]. Later on, glucose $5\mathrm{\%}$ injections were used to treat other forms of musculoskeletal pain [lii, liv, lv]. Some physicians also used glucose $5\mathrm{\%}$ injections for tennis elbow [lvi], tension headache, postherpetic neuralgia, and Dupuytren's stage 1. As the total amount of glucose is very small (similar to eating a few strawberries once a week), glucopuncture can be applied for patients who are diabetic or those who are on a strict calorie diet.

X. DIFFERENCE BETWEEN GLUCOPUNCTURE AND PROLOTHERAPY

Glucose and dextrose injections have been used for several decades in prolotherapy [lvii, lviii, lix, lx, lxi, lxii, lxiii, lxiv]. Prolotherapy injects hypertonic dextrose (10% net concentration or more) into, for example, entheses of ligaments, bands and tendons. Injections into periost and into joint cavities are also given. Hyperosmolar solutions lead to localized cell shrinking and subsequent cell destruction. This phenomenon creates release of arachidonic acid (from the cell membrane) which creates a local inflammatory reaction. The latter may lead to local tissue proliferation - hence the description prolotherapy - and even formation of scar tissue [lxv]. Local anesthetics are always added to make the injections less painful.

Glucopuncture also injects glucose (or dextrose) but only in an isotonic concentration $(5\mathrm{\%})$. As a result, there is no local osmotic shock, no cell death, no subsequent inflammatory reaction. That is why the ATP hypothesis was required to explain the pain modulating effects of glucopuncture, as well as the positive effect of glucose $5\mathrm{\%}$ injections on tissue repair (as in Dupuytren's stage 1). The injection techniques are also different. Glucopuncture typically uses more shallow injections than prolotherapy. Most of the injections are given in the dermis, and also in trigger points of muscles and ligaments. In contrast to prolotherapy, local anesthetics are never added to the solution (Table 1).

XI. INTRADERMAL GLUCOSE $5\mathrm{\%}$ INJECTIONS FOR LOCALIZED NEUropATHIC PAIN

During questioning, the patient is asked to point out the zone of pain referral. Sometimes the physician can localize pain points within the pain region which are extra sore. Such points may receive an extra dose of injectate. The treatment itself is remarkably simple and straightforward. The injection procedure itself typically takes less than a minute to perform. After identifying the tender zone, one gives multiple intradermal injections (intracutaneous wheals) with glucose $5\mathrm{\%}$ in the pain region, as indicated by the patient. Intracutaneous injections usually feel like sharp stings for a few seconds. Intracutaneous injections (IC) are more painful than subcutaneous injections (SC) but IC injections seem to be more effective regarding modulation of neuropathic pain. Some patients have a very thin epidermis, which makes IC injections impossible, so one has to rely on SC injections instead. The injections are usually given 1 cm apart. About 0.5 to 1 mL is given in each spot with a 30 G or 27 G needle. The total volume per session is usually between 2 and 20 mL, depending on the size of the tender region. It often happens that the patient experiences immediate pain relief a few seconds or minutes after the glucose $5\mathrm{\%}$ injections. This is rather surprising, as no local anesthetics are added to the glucose. Unfortunately, this pain modulating effect of glucose $5\mathrm{\%}$ lasts only for a few hours to a few days. In some patients, the symptomatic improvement only becomes apparent after the second or third session. To obtain long term results, repetition is required until lasting pain relief has been achieved.

XII. CONCLUSION

In the search for treatment modalities which are safe, affordable and effective, several clinicians worldwide have experienced that glucose $5\mathrm{\%}$ injections are an inexpensive treatment to reduce their patient's intake of pain medication. This is especially true for mild forms of regional neuropathic pain. More research in this field may confirm their clinical findings.

Table-1

• ${}^{xii}$ Eliav E, Benoliel R, Herzberg U, Kalladka M, Tal M. The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis. Brain Behav Immun. 2009 May;23(4):474-84. doi: 10.1016/j.bbi.2009.01.012. Epub 2009 Jan 29. PubMed PMID: 19486649

• ${}^{\text{xiii }}$ Jensen T.S., Baron R., Haanpää M., Kals O., Loeser J.D., Rice A.S., Treede R.-D. A new definition of neuropathic pain. Pain. 2011; 152:2204-2205. doi: 10.1016/j.pain.2011.06.017

• ${}^{xiv}$ Kocot-Kepska M, Zajaczkowska R, Mika J, et al. Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review. Pharmaceutics. 2021;13(4):450. Published 2021 Mar 26. doi:10.3390/pharmaceutics13040450

• Sauer SK, Bove GM, Averbeck B, Reeh PW, Rat peripheral nerve components release calcitonin gene-related peptide and prostaglandin E2 in response to noxious stimuli: Evidence that nervi nervorum are nociceptors. Neuroscience 1999; 92(1): 319-25

• Xvi Kiguchi N, Maeda T, Kobayashi Y, Fukazawa Y, Kishioka S. Macrophage inflammatory protein-1alpha mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1beta up-regulation. Pain. 2010 May;149(2):305-315. doi: 10.1016/j.pain.2010.02.025. Epub 2010 Mar 12. PMID: 20223588.

• ${}^{xvii}$ Sauer SK, Bove GM, Averbeck B, Reeh PW, Rat peripheral nerve components release calcitonin gene-related peptide and prostaglandin E2 in response to noxious stimuli: Evidence that nervi nervorum are nociceptors. Neuroscience 1999; 92(1): 319-25

• ${}^{\text{xviii }}$ Kessler A, Yoo M, Calisoff R. Complex regional pain syndrome: An updated comprehensive review. Neuro Rehabilitation. 2020;47(3):253-264. doi:10.3233/NRE-208001. PMID: 32986618.

• ${}^{\text{ix}}$ Iqbal Z, Azmi S, Yadav R, Ferdousi M, Kumar M, Cuthbertson DJ, Lim J, Malik RA, Alam U. Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy. Clin Ther. 2018 Jun;40(6):828-849. doi: 10.1016/j.clinthera.2018.04.001. Epub 2018 Apr 30. PMID: 29709457.

• ${}^{\text{xx}}$ Gilron I, Baron R, Jensen T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin Proc. 2015 Apr;90(4):532-45. doi: 10.1016/j.mayocp.2015.01.018. PMID: 25841257.

• ${}^{xxi}$ Plancarte-Sanchez R, Samano-Garcia M, Guillen-Nunez MDR, Equihua-Ortega A. Localized neuropathic pain. Gac Med Mex. 2021;157(3):302-308. English. doi: 10.24875/GMM.M21000562. PMID: 34667330.

• xxii Pickering G, Martin E, Tiber ghien F, Delorme C, Mick G. Localized neuropathic pain: an expert consensus on local treatments. Drug Des DevelTher. 2017 Sep 13; 11:2709-2718. doi: 10.2147/DDDT.S142630. PMID: 29066862; PMCID: PMC5604568.

• xxiii Allegri M, Baron R, Hans G, Correa-Illanes G, Mayoral Rojals V, Mick G, Serpell M. A pharmacological treatment algorithm for localized neuropathic pain. Curr Med Res Opin. 2016;32(2):377-84. doi: 10.1185/03007995.2015.1129321. PMID: 26641136.

• xxiv Xu L, Zhang Y, Huang Y. Advances in the Treatment of Neuropathic Pain. Adv Exp Med Biol. 2016; 904:117-29. doi: 10.1007/978-94-017-7537-3_9. PMID: 26900067.

• xxv Güzel i, Gül D, Akpancar S, Lyftogt J. Effectiveness of Perineural Injections Combined with Standard Postoperative Total Knee Arthroplasty Protocols in the Management of

• Chronic Postsurgical Pain After Total Knee Arthroplasty. Med Sci Monit. 2021 Feb 6;27: e928759. doi: 10.12659/MSM.928759.PMID:33547269; PMCID:PMC7874529.

• ${}^{xxv}$ Wu YT, Chen YP; Lam KHS; Reeves KD, Lin JA; Kuo CY, Mechanism of Glucose Water as a Neural Injection: A Perspective on Neuroinflammation. Life 2022, 12, 832

• xxvii Wu, Y.T., et al., Six-month Efficacy of Perineural Dextrose for Carpal Tunnel Syndrome: A Prospective, Randomized, Double-Blind, Controlled Trial. Mayo Clin Proc, 2017. 92(8): p. 1179-1189

• Kersschot J, Treatment of Sports Injuries with Gluco puncture. Archives in Biomedical Engineering & Biotechnology 5(1): 2021

• xxix Mergenthaler, Philipp et al. "Sugar for the brain: the role of glucose in physiological and pathological brain function." Trends in neurosciences vol. 36,10 (2013): 587-97. doi: 10.1016/j.tins.2013.07.001

• xxx Howarth C, et al. Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab. 2012; 32:1222-1232.

• ${}^{xxx}$ Erbsloh F, et al. [The glucose consumption of the brain & its dependence on the liver] Arch Psychiatr Nervenkr Z Gesamte Neurol Psychiatr. 1958; 196:611-626

• xxii Mergenthaler, Philipp et al. "Sugar for the brain: the role of glucose in physiological and pathological brain function." Trends in neurosciences vol. 36,10 (2013): 587-97. doi: 10.1016/j.tins.2013.07.001

• xxiii Mergenthaler, Philipp et al. "Sugar for the brain: the role of glucose in physiological and pathological brain function." Trends in neurosciences vol. 36,10 (2013): 587-97.doi: 10.1016/j.tins.2013.07.001

• xxxiv Harris JJ, et al. Synaptic energy use and supply. Neuron.2012;75:762-777

• xxxx Ivannikov MV, et al. Calcium clearance and its energy requirements in cerebellar neurons. Cell Calcium. 2010; 47:507-513

• xxvi Dienel GA. Fueling and imaging brain activation. ASN Neuro. 2012;4: e00093

• xxxvii 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.

• xxxviii Bove GM, Dilley A. The conundrum of sensitization when recording from nociceptors. J Neurosci Methods. 2010 May 15;188(2):213-8. doi: 10.1016/j.jneumeth.2010.02.010. Epub 2010 Feb 18. PubMed PMID: 20171245; PubMed Central PMCID: PMC2854223.

• xxxix Wade NJ. Microscopic anatomy of sensory receptors. J Hist Neurosci. 2019 Jul-Sep;28(3):285-306. doi: 10.1080/0964704X.2018.1554298. Epub 2019 Mar 11. PMID: 30856054.

• ${}^{\text{xl}}$ Handler A, Ginty DD. The mechanosensory neurons of touch and their mechanisms of activation. Nat Rev Neurosci. 2021 Sep;22(9):521-537. doi: 10.1038/s41583-021-00489-x. Epub 2021 Jul 26. PMID: 34312536; PMCID: PMC8485761.

• ${}^{\text{xi}}$ Wade NJ. Microscopic anatomy of sensory receptors. J Hist Neurosci. 2019 Jul-Sep;28(3):285-306. doi: 10.1080/0964704X.2018.1554298. Epub 2019 Mar 11. PMID: 30856054.

• ${}^{\text{X}}$ Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018 May;40(3):249-259. doi: 10.1007/s00281-018-0675-z. Epub 2018 Apr 30. PMID: 29713744; PMCID: PMC6047518.

• xiii Tavee J. Nerve conduction studies: Basic concepts. Handb Clin Neurol. 2019; 160:217-224. doi: 10.1016/B978-0-444-64032-1.00014-X. PMID: 31277849.

• xiv Dubin AE, Pata poutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010 Nov;120(11):3760-72. doi: 10.1172/JCI42843. Epub 2010 Nov 1. PMID: 21041958; PMCID: PMC2964977.

• ${}^{\text{IV}}$ Filtjens J, Roger A, Quatrini L, Wieduwild E, Gouilly J, Hoeffel G, Rossignol R, Daher C, Debroas G, Henri S, Jones CM, Malissen B, Mackay LK, Moqrich A, Carbone FR, Ugolini S. Nociceptive sensory neurons promote CD8 T cell responses to HSV-1 infection. Nat Commun. 2021 May 18;12(1):2936. doi: 10.1038/s41467-021-22841-6. PMID: 34006861; PMCID: PMC8131384.

• xvi Maglie R, Souza Monteiro de Araujo D, Antiga E, Geppetti P, Nassini R, De Logu F. The Role of TRPA1 in Skin Physiology and Pathology. Int J Mol Sci. 2021 Mar 17;22(6):3065. doi: 10.3390/ijms22063065. PMID: 33802836; PMCID: PMC8002674.

• xvii Wu D, Lee S, Luo J, Xia H, Gushchina S, Richardson PM, Yeh J, Krügel U, Franke H, Zhang Y, Bo X. Intraneural Injection of ATP Stimulates Regeneration of Primary Sensory Axons in the Spinal Cord. J Neurosci. 2018 Feb 7;38(6):1351-1365.

• ${}^{xviii}$ Moriyama M, Kitamura A, Ikezaki H, Nakanishi K, Kim C, Sakamoto A, Ogawa R. Systemic ATP infusion improves spontaneous pain and tactile allodynia, but not tactile hypesthesia, in patients with postherpetic neuralgia. J Anesth. 2004;18(3):177-80. doi: 10.1007/s00540-004-0240-x. PMID: 15290415.

• xix Hayashida M, Fukuda K, Fukunaga A, Meno A, Sato K, Tarui K, Arita H, Kaneko Y, Hanaoka K. Analgesic effect of intravenous ATP on postherpetic neuralgia in comparison with responses to intravenous ketamine and lidocaine. J Anesth. 2005;19(1):31-5. doi: 10.1007/s00540-004-0273-1. PMID: 15674513.

• ${}^1$ Fukuda K, Hayashida M, Fukunaga A, Kasahara M, Koukita Y, Ichinohe T, Kaneko Y. Pain-relieving effects of intravenous ATP in chronic intractable orofacial pain: an open-label study. J Anesth. 2007;21(1):24-30. doi: 10.1007/s00540-006-0444-3. Epub 2007 Jan 30. PMID: 17285409.

• Sawynok J. Adenosine and ATP receptors. HandbExpPharmacol. 2007;(177):309-28 doi:10.1007/978-3-540-33823-9 11. PMID 17087128.

• [^31] Lyftogt J. Prolotherapy and Achilles tendinopathy: a prospective pilotstudy of an old treatment. AustralasMusculoskel Med. 2005; 10:16-19.

• Koroglu O, Ors A, Karasimav O, Demir Y, Solmaz I, Is 5% dextrose prolotherapy effective for radicular low back pain? Gulhane Medical Journal 2019; 61 (3): 123-127.

• ${}^{\text{iv}}$ Lyftogt, J., Subcutaneous prolotherapy treatment of refractory knee, shoulder, and lateral elbow pain. Australasian Musculoskel Med. 2007; 12 (1), 107-109

• ^IV Amanollahi A., Asheghan M., Hashemi S, Subacromial corticosteroid injection versus subcutaneous $5\mathrm{\%}$ dextrose in patients with chronic rotator cuff tendinopathy: A short-term randomized clinical trial, Interventional Medicine and Applied Science IMAS 2020, 11(3), 154-160

• Kersschet J, Management of Lateral Elbow Pain with Glucopuncture. Global Journal of Orthopedics Research 3(1): 2021

• ^IV Reeves KD, Sit RW, Rabago DP. Dextrose Prolotherapy: A Narrative Review of Basic Science, Clinical Research, and Best