Saudi Journal of Anaesthesia

: 2021  |  Volume : 15  |  Issue : 4  |  Page : 463--465

Prolotherapy as an intervention for chronic, refractory musculoskeletal pain

Abhijit Nair 
 Department of Anaesthesiology, Ibra Hospital, Ministry of Health-Oman, Sultanate of Oman

Correspondence Address:
Abhijit Nair
Department of Anaesthesiology, Ibra Hospital, Ministry of Health-Oman, P.O. Box 275, Ibra-414
Sultanate of Oman

How to cite this article:
Nair A. Prolotherapy as an intervention for chronic, refractory musculoskeletal pain.Saudi J Anaesth 2021;15:463-465

How to cite this URL:
Nair A. Prolotherapy as an intervention for chronic, refractory musculoskeletal pain. Saudi J Anaesth [serial online] 2021 [cited 2022 Oct 5 ];15:463-465
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Full Text

To the Editor,

Proliferative injection therapy or prolotherapy, also called regeneration therapy, is an interventional modality used for various chronic painful musculoskeletal conditions. Prolotherapy involves a small volume of local anesthetic injections with or without a sclerosing or irritant agent into the connective tissues between the ligament or tendon and bone, or intra-articular space. These injections can be repeated based on the requirement. The mechanism of the action of prolotherapy is postulated as by activation of an inflammatory response at the site of the injection, increasing levels of growth factors after injections as a result of which there will be regenerative processes in cells in the vicinity. It is also postulated that there is stimulation of fibroblast and vascular proliferation, deposition of dense collagen, and cartilage growth around the area of injection. This modality has not become very popular because it is used as the last weapon from the armamentarium of pain physicians when all other therapies like medications, various other interventional procedures, and other alternative therapies have failed. The existing literature is heterogenous, has a small sample size, is not adequately powered, and is in the form of case reports/series.[1]

There are several published papers in which prolotherapy was successfully used in managing chronic pain due to various etiologies like knee osteoarthritis, Achilles tendinopathy, coccygodynia, lateral epicondylosis, degenerative disk disease, low back pain, plantar fasciitis, and chronic sacroiliac joint pain.[2] Various solutions are used for injections in prolotherapy. Although hyperosmolar dextrose (15–25%) is the most commonly used solution, other agents like morrhuate sodium and phenol-glycerin-glucose (P2G) have also been used for prolotherapy.

Johnston et al.[3] used P2G for prolotherapy in cultured murine MC3T3-E1 cells. The authors demonstrated that there was an upregulation of the cartilage cell proliferation enhancer cytokine FGF-2, suggesting an independent effect of P2G. In a randomized controlled trial by Rabago et al.,[4] the authors compared dextrose prolotherapy in 90 patients with chronic knee osteoarthritis with control as saline and home exercises. Interventions were performed on 1st, 5th, and 9th week using 15–25% dextrose solution. On analysis, the authors concluded that there was a more sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with saline injections and at-home exercise. The authors recommended dextrose prolotherapy in patients who were refractory to all other conservative modalities for managing pain due to chronic osteoarthritis. Later, Rabago et al. performed prolotherapy in 38 patients with moderate-to-severe knee osteoarthritis using extra-articular injections of 15% dextrose and 5% morrhuate sodium at the peri-articular tendon and ligament insertions.[5] Along with this, they also performed a single intra-articular injection of 6 mL 25% dextrose through an inferomedial approach. The injections were performed at 1,5, and 9 weeks and later the patients were followed up. On analysis, the authors concluded that injections using the above-mentioned approach resulted in safe, significant, and sustained improvement of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-based knee pain, function, and stiffness scores compared to the pain at the baseline. [Table 1] summarizes the recent systematic review and meta-analysis published, which has reviewed the existing data and given their verdict.{Table 1}

At present, there is no formal training program for becoming a prolotherapist. Pain physicians, orthopedic surgeons, podiatrists, and primary care physicians are performing the interventions. The scope of learning and practicing prolotherapy is by reviewing the available literature, understanding the injection techniques by attending workshops and courses, selecting the patient appropriately, and following up with the patient so as to know the benefits, harm, or any adverse effects due to the injections done.

To conclude, at present, the evidence of prolotherapy being an effective intervention in chronic musculoskeletal pain appears anecdotal and is not supported by a robust, adequately-powered randomized controlled trial. However, the intervention is indeed safe and has provided relief when all evidence-based, multimodal approaches failed in allaying pain. Well-designed studies with less heterogenicity are required to further explore the scope of prolotherapy.[8]

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Conflicts of interest

There are no conflicts of interest.


1Krstičević M, Jerić M, Došenović S, Jeličić Kadić A, Puljak L. Proliferative injection therapy for osteoarthritis: A systematic review. Int Orthop 2017;41:671-9.
2Bae G, Kim S, Lee S, Lee WY, Lim Y. Prolotherapy for the patients with chronic musculoskeletal pain: Systematic review and meta-analysis. Anesth Pain Med (Seoul) 2021;16:81-95.
3Johnston E, Emani C, Kochan A, Ghebrehawariat K, Tyburski J, Johnston M, et al. Prolotherapy agent P2G is associated with upregulation of fibroblast growth factor-2 genetic expression in vitro [published correction appears in J Exp Orthop. 2020;7:100]. J Exp Orthop 2020;7:97.
4Rabago D, Patterson JJ, Mundt M, Kijowski R, Grettie J, Segal NA, et al. Dextrose prolotherapy for knee osteoarthritis: A randomized controlled trial. Ann Fam Med 2013;11:229-37.
5Rabago D, Patterson JJ, Mundt M, Zgierska A, Fortney L, Grettie J, et al. Dextrose and morrhuate sodium injections (prolotherapy) for knee osteoarthritis: A prospective open-label trial. J Altern Complement Med 2014;20:383-91.
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7Arias-Vázquez PI, Tovilla-Zárate CA, Legorreta-Ramírez BG, Burad Fonz W, Magaña-Ricardez D, González-Castro TB, et al. Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: Systematic review of clinical trials. Adv Rheumatol 2019;59:39.
8Chung MW, Hsu CY, Chung WK, Lin YN. Effects of dextrose prolotherapy on tendinopathy, fasciopathy, and ligament injuries, fact or myth?: A systematic review and meta-analysis. Medicine (Baltimore) 2020;99:e23201.