The use of prolotherapy in temporomandibular disorders

ABSTRACT

BACKGROUND AND OBJECTIVES  The search for minimally invasive treatments for temporomandibular disorders (TMD) has increased in recent years. Prolotherapy, which uses irritant solutions to induce controlled inflammation and tissue regeneration, has emerged as a promising alternative. This article reviews its mechanisms of action, indications, contraindications, application formulas, and clinical outcomes.

CONTENTS  In recent years, research has focused on clinical and minimally invasive treatments for TMD, as well as on determining when and how to apply them effectively. Prolotherapy stands out as a minimally invasive approach that is cost-effective, performed under local anesthesia, replicable, and associated with low morbidity. Its application aims to relieve or eliminate pain and joint dysfunction, making it a promising option in such cases.

CONCLUSION  Prolotherapy, based on the use of dextrose in varying concentrations, has shown encouraging results in the treatment of Temporomandibular Disorders (TMD), particularly in cases of myofascial pain, joint hypermobility, and disc displacement with reduction. By promoting tissue regeneration and stabilizing the temporomandibular joint (TMJ), this technique offers a less invasive alternative with long-lasting results. However, further studies are essential to standardize treatment protocols and to explore its specific indications and contraindications in more detail.

Keywords:
Temporomandibular joint; Temporomandibular dysfunction; Prolotherapy

HIGHLIGHTS

Prolotherapy with hypertonic glucose is effective in treating myofascial pain, hypermobility, subluxation, and temporomandibular joint disc displacement with reduction

Prolotherapy stimulates growth factors, promoting connective tissue repair and reducing or eliminating pain

Intra-articular injections are minimally invasive procedures that can be used for temporomandibular disorders that are refractory to even more conservative therapies

RESUMO

JUSTIFICATIVA E OBJETIVOS  A busca por tratamentos minimamente invasivos para disfunções temporomandibulares (DTM) tem crescido nos últimos anos. A proloterapia, que utiliza soluções irritantes para induzir inflamação controlada e regeneração tecidual, surge como alternativa promissora. Este artigo analisa seus mecanismos de ação, indicações, contraindicações, fórmulas de aplicação e resultados clínicos.

CONTEÚDO  Nos últimos anos, pesquisas têm se concentrado em tratamentos clínicos e minimamente invasivos para as DTM, assim como quando e como empregá-los. A proloterapia destaca-se como uma abordagem minimamente invasiva, de baixo custo, realizada sob anestesia local, replicável e com baixa morbidade. Sua aplicação visa aliviar ou eliminar a dor e a DTM, sendo uma opção promissora nesses casos.

CONCLUSÃO  A proloterapia, baseada no uso de dextrose em diferentes concentrações, apresenta resultados encorajadores no tratamento das disfunções da articulação temporomandibular (DTM), especialmente em casos de dor miofascial, hipermobilidade articular e deslocamento do disco com redução. Ao estimular a regeneração tecidual e estabilizar a articulação temporomandibular (ATM), a técnica oferece uma alternativa menos invasiva com resultados duradouros. Contudo, é fundamental que mais estudos sejam conduzidos para padronizar protocolos, além de explorar de forma mais detalhada as indicações e contraindicações específicas.

Descritores:
Articulação temporomandibular; Disfunção temporomandibular; Proloterapia

DESTAQUES

A proloterapia, com glicose hipertônica, é eficaz no tratamento da dor miofascial, da hipermobilidade, da subluxação e do deslocamento do disco da articulação temporomandibular com redução

A proloterapia estimula fatores de crescimento, com reparação do tecido conjuntivo, reduzindo ou eliminando a dor

As injeções intra-articulares são procedimentos minimamente invasivos que podem ser empregados nas disfunções temporomandibulares refratárias a terapias ainda mais conservadoras

INTRODUCTION

Temporomandibular disorders (TMD) encompass clinical conditions that affect the temporomandibular joint (TMJ), masticatory muscles and associated structures, causing pain, limited movement and joint noise, it is also one of the main causes of orofacial pain¹-³ . Several treatments have been proposed to manage these conditions, including conservative treatments such as the use of occlusal plates, pharmacotherapy, physiotherapy, minimally invasive approaches such as arthrocentesis and arthroscopy, and more invasive ones such as arthrotomy⁴ .

In recent years, prolotherapy (PR) has been highlighted in the field of TMD management, especially in cases refractory to conventional treatments. Also known as injection regeneration therapy, it uses irritating substances such as dextrose (PRD) to induce controlled inflammation and stimulate tissue regeneration⁵-⁸ . The present study’s objective was to discuss the mechanisms of action, indications, contraindications, dextrose concentrations, application protocol, complications and clinical results in TMD.

CONTENTS

The searches were conducted in the Pubmed, SCOPUS and CINAHL databases for articles published between 1956 and 2024. The following keywords were selected using the National Library of Medicine's MeSH terms in combination: Prolotherapy, Disc displacement with reduction, TMD pain, TMJ disorders, Occlusal splint, Physiotherapy, TMJ injectable agents, Recurrent TMJ dislocation, Hypermobility disorders of TMJ and Myofascial trigger points. In addition, two anatomy textbooks in Portuguese were included in the search, as well as original articles and reviews in English and German that had clinical relevance and practical validity in terms of the possibility of application in the treatment of TMD. Articles that did not involve a practical aspect or that did not present some degree of evidence were excluded. A first selection was made by reviewing the titles and abstracts of all articles found. Next, the full texts of potentially suitable articles were evaluated. According to these criteria, 54 articles were included.

Mechanism of action

PR induces low-grade inflammation through hyperosmolar solutions. Glucose activates GLUT 1-4 channels, promoting the release of water and lipids and triggering temporary inflammation mediated by cytokines⁹ . Activation of granulocytes, macrophages, chondrocytes, nerve cells and fibroblasts leads to collagen deposition and contraction, reducing ligament laxity. In addition, the tissue injury caused by the needle stimulates repair through the release of growth factors (platelet, basic fibroblast and insulin-like) and inflammatory mediators (CGRP, bradykinin and prostaglandins)¹⁰ . Administration of hyperosmotic solutions, such as dextrose, activates pain receptors, including those of capsaicin, increasing substance P, CGRP and nitric oxide, which can exert negative regulation on these receptors¹¹ .

Another mechanism involved is tissue glycosylation, which occurs when glucose reacts, not evolving enzymes, with proteins, lipids or nucleic acids, generating advanced glycation end products (AGEs). These AGEs activate receptors such as RAGE, amplifying inflammatory signaling via NF-κB, which stimulates the production of pro-inflammatory cytokines (IL-1β, TNF-α and IL-6). The presence of AGEs also recruits macrophages and immune cells, which release growth factors (TGF-β and VEGF), promoting angiogenesis, tissue regeneration, fibroblast proliferation and extracellular matrix deposition. This process results in fibroplasia and greater ligament stability, which may explain the positive effects of PR on soft tissue repair and reduction of ligament laxity¹⁰ .

Indications

PRD has been indicated in some cases of TMD, especially in patients with myofascial pain¹² , disc displacement with reduction¹³,¹⁴ , joint hypermobility¹⁵-¹⁸ or TMJ subluxation¹⁹ .

Contraindications

Although PRD is safe and minimally invasive, there are contraindications, such as systemic or local bacterial infection, use of anticoagulants, needle phobia, musculoskeletal neoplasms, recent progressive neurological deficit, excessive need for sedation, progressive pain unresponsive to anesthetic blocks and allergy to injectable components such as dextrose (corn), sodium morruate (fish) or phenol²⁰ .

Concentration

Several authors have used different concentrations of dextrose in PR to treat joint TMD. Solutions with concentrations of 10%²¹ , 20%¹⁷ , 25%¹⁰ , 30%¹⁶ and even 50%¹⁵ have been used. The choice of the dextrose concentration in PR depends on the objective of the treatment, the type of tissue treated and the desired mechanism, whether proliferative or inflammatory. Concentrations below 10% stimulate tissue proliferation without significant inflammation, promoting the deposition of extracellular matrix. Intermediate concentrations (20%-25%) induce controlled inflammation, favoring moderate regeneration. Higher solutions (30%-50%) are used for thick structures, such as joint capsules and ligaments, due to their greater osmotic effect, stimulating the release of inflammatory factors and the healing cascade. High concentrations are indicated for severe ligament laxity or recurrent dislocations of the mandibular head, while lower concentrations are preferable for myofascial pain, minimizing discomfort and adverse effects. However, there is no consensus on the ideal concentration, the choice being based on the clinician's experience and the protocol adopted¹⁰,¹⁵-¹⁷,²¹ .

Number, volume and sites injected

Studies vary widely as for the number and volume and sites of injections in PR for joint TMD. A single injection site has been used with volumes of 2 mL and 1 mL, respectively, in the superior posterior ligament of the retrodiscal tissue¹⁰,¹⁵ . Three injection sites have been applied, with 2 mL in the superior capsular ligament, located on the lateral margin of the mandibular fossa; in the inferior capsular ligament, close to the mandibular neck; and in the superior compartment of the TMJ²¹ .

A four-point injection protocol was used: 1 mL in the posterior insertion of the disc with an opening of 10 mm, 1 mL in the superior articular space after maximum opening, and 0.5 mL in the lateral margin of the mandibular fossa and in the mandibular neck at the superior and inferior capsular insertions¹⁷ . Five injection points were used: superior articular space, superior and inferior capsular ligaments, posterior superior disc ligament and stylomandibular ligament (Figure 1), with 1 mL of dextrose solution at each site. The protocol included three monthly sessions, using 2 mL of 30% dextrose, 2 mL of saline solution and 1 mL of 2% articaine or mepivacaine for local anesthesia and patient comfort¹⁶ .

Figure 1
Injection points. Adapted¹⁶ . 1. posterior insertion of the disc; 2. superior capsular insertion; 3. superior articular space; 4. inferior capsular insertion; 5. stylomandibular ligament; 6. origin of the masseter muscle.

Complications

Dextrose, derived from corn, is contraindicated for allergy sufferers. The injection, with a penetration of about one inch, minimizes intravascular risks with prior aspiration. Mild hematomas may occur, especially in light-skinned patients or those with difficulties in anatomical localization¹³ .

Preparation of the operating field, solution used and injection

With a professional wearing a mask, apron and sterile gloves, the area is antiseptically treated with 0.12% chlorhexidine, sterile drapes are placed and the injection points are marked in the TMJ region with a sterile pen. The injection may or may not be preceded by a regional anesthetic block of the temporal auricle nerve or at the injection site, depending on the technique and solution used⁹,¹⁰ . PRD infiltration is similar to intra-articular injection in TMJ arthrocentesis. Injections in the face and TMJ must be minimally traumatic due to the rich local innervation, and it is recommended to use a 30G needle and concentrations of 10% to 50% dextrose, depending on the professional's experience. If the option is 12.5% dextrose, the solution should be prepared in a 3 mL syringe, using a 25G needle to aspirate 0.75 mL of 50% dextrose, 0.75 mL of distilled water and 1.5 mL of 2% lidocaine. The air must then be removed and the needle used for aspiration must be replaced with a 30G²²-²⁵ needle before the procedure is carried out.

It begins in the posterior articular space. The lateral pole of the mandibular head is palpated while the patient opens and closes their mouth, identifying the depression anterior to the tragus. The point is marked and the needle is inserted at 2.5 cm, directed anteromedially towards the medial wall of the mandibular fossa. After aspiration to avoid vessels, 1 mL of the solution is injected. Next, the injection is made into the anterior portion of the disc and the upper head of the lateral pterygoid muscle. To locate this area, the physician should observe the slight depression anterior to the mandibular head with the mouth closed and mark this point before the first injection, as palpation can be difficult.

The needle is inserted into the marked point, angled anteromedially, at the same depth, followed by aspiration and injection of 1 mL of the solution. The third point corresponds to a myofascial trigger point (MTP) at the origin of the masseter muscle near the zygomatic arch. So that it is easier to locate, the patient is asked to clench their teeth, outlining the muscle. The most sensitive point is marked. The patient then relaxes their jaw and 1 mL of the solution is injected directly into the area, using the same depth as the needle. The objective of this protocol is to guarantee precision in the application, optimizing the therapeutic effects and minimizing discomfort for the patient¹³ . Once the injections are complete, the areas marked with the pen are removed. This procedure is carried out three times, at fortnightly or monthly intervals, depending on how the case progress⁴,¹³,¹⁶ . It is recommended that the patient returns for evaluations after 30, 90 and 180 days¹⁵,²⁶ .

CLINICAL RESULTS

The effectiveness of PRD in the treatment of TMD will be analyzed below, with specifications for each relevant condition.

Myofascial pain

One study included 64 patients with myofascial pain, who were divided into three groups for injections in the MTP: 5% aqueous dextrose (Group DA, n=23), saline solution (Group SS, n=20) and 0.5% lidocaine (Group L, n=21). Pain was evaluated using the Visual Analog Scale (VAS) and the pressure threshold using an algometer, before, immediately after and seven days after the injections. The mean pain intensity was 6.78 before, 5.19 immediately after and 3.39 after seven days, with a greater effect after the second and third injections. The pressure threshold increased by 0.37 immediately after and by 0.42 after seven days. After one week, only the DA Group had a significant reduction in the VAS score (2.39 vs. 3.85 in the SS and 4.05 in the L, p<0.01) and a significant increase in the pressure threshold (2.49 vs. 1.91 in the SS and 2.07 in the L, p<0.05). The authors concluded that 5% dextrose is the best option for injection in the MTP¹² .

Disc displacement with reduction

A study compared the effectiveness of two different treatments: PRD12.5% and deep dry needling therapy (DDNT) in a sample of 40 patients with anterior disc displacement with reduction (ADDR). This randomized clinical trial evaluated the impact of each therapy on pain relief, functional improvement and patient symptoms. The results indicated that both treatments were effective in improving symptoms related to ADDR. However, PRD showed superior effects in terms of pain relief, improved jaw function and symptom reduction compared to DDNT. This suggests that PRD may be a more effective option for treating this condition, offering more significant clinical benefits¹⁴ .

Subluxation

A randomized clinical trial compared botulinum toxin A (TxB-A) and PRD in 30 adults with TMJ subluxation, 25 of whom completed the study. The TxB-A group (n=11, mean age 25.64 years) received 40U in the lateral pterygoid muscles, while the PRD group (n=14, mean age 32.37 years) received three sessions of injections around the TMJ. The frequency of locking was assessed at the beginning and after 8-12 months, and patient satisfaction only at the end. Both groups showed a significant reduction in locking episodes (p<.01), with no difference between them (p>.05). Seven patients in the TxB-A group (63.6%) and eight in the PRD group (57.1%) did not report locking episodes, with similar satisfaction in both groups (p>.05). The findings indicate that PRD and TxB-A are equally effective in reducing locking and patient satisfaction¹⁹ .

Another randomized clinical trial¹⁷ evaluated different concentrations of PRD at 10%, 20% and 30% versus saline as a placebo in the treatment of TMJ hypermobility in 40 patients with mandibular subluxation or dislocation. All received injections in four areas of the TMJ for four months. After treatment, all groups showed an improvement in pain, a reduction in mouth opening and joint sounds, with no episodes of locking. There were no statistical differences between the groups, indicating that no concentration of dextrose was superior to the placebo.

Joint hypermobility

A randomized clinical trial evaluated PRD compared to placebo in the treatment of TMJ hypermobility. Of the 30 patients recruited, 26 completed the study, 12 in the placebo group and 14 in the PRD group. The placebo group received saline injections, while the PRD group received 30% dextrose, both administered in five ligament and joint areas. Pain was assessed by the VAS, and maximum interincisal opening (MIO) was measured preoperatively and after 12 months. Both groups showed improvement in pain and joint sounds, with an increase in masticatory efficiency. However, MIO was significantly reduced only in the PRD group. There were no statistically significant differences between the groups in the primary outcome variables, suggesting that PRD was not superior to placebo in the treatment of TMJ hypermobility¹⁶ .

DISCUSSION

Joint diseases such as disc dislocations, hypermobility, subluxation and dislocation of the TMJ should always be treated conservatively first. Various therapies are indicated, such as the use of occlusal devices and manual therapy, low-intensity photobiomodulation and isolated arthrocentesis²⁷-³² . When these therapies fail, an interesting option may be the use of PRD¹²-¹⁹,²¹ . PRD involves intra- and periarticular injections to strengthen the TMJ capsule and ligaments, promoting fibroblast proliferation and relief of pain. In cases of subluxation and disc displacement, it offers advantages such as: being less invasive, being performed in an outpatient setting, low cost, rapid execution and lower risk of morbidity, such as facial nerve damage. However, it requires multiple applications and there is still little data on its long-term effects, especially on articular cartilage²⁷ .

The concentration of dextrose can determine whether it will have an inflammatory characteristic or not. Some authors mention that when the concentration of dextrose is below 10%, it directly promotes cell and tissue proliferation without causing inflammatory reactions¹⁵,²¹ . On the other hand, when the concentration is higher than 10%, it generates local tissue trauma due to its osmotic effect, which triggers inflammatory reactions, stimulating healing and tissue repair. One possible mechanism attributed to glucose is its ability to increase the proliferation of osteoblasts and chondroblasts from synovial tissue progenitor cells, which could contribute to the repair of TMJ intra-articular structures³³-⁴⁰ .

It is possible that there is an association between the injection site and a positive outcome¹⁵,⁴¹-⁴⁴ . It is recommended that in cases of joint hypermobility, intracapsular injection should be used⁴⁵-⁴⁸ . However, when there is pain, joint hypomobility, disc displacement and joint sounds, the best options are injection into the retrodiscal tissue and into the superior or inferior compartments of the TMJ. When joint hypomobility is present, especially if it is related to adhesions or early-stage adhesions, injecting dextrose will only increase this joint condition, due to the increase in local fibroplasia. In this case, the indication is for arthrocentesis or other surgical treatments³²,⁴⁹,⁵⁰-⁵² . If the option is to inject dextrose into the lower compartment, when disc displacement and joint sounds are present, it should be done with ultrasound guidance⁵³ . In the case of pathological changes in this joint, there may be adhesions between the upper pole of the mandibular head and the lower portion of the disc, which further reduces the volume of the lower compartment, making the needle penetration and injection more difficult.

PRD is a viable, effective, low-cost and safe option. It is well accepted by patients and has no significant adverse effects²¹ . When comparing PRD with TMJ arthrocentesis, the two are similar in that they use needle injections, however, PRD mainly injects dextrose in varying concentrations⁵⁴ alone¹⁷ or combined with anesthetics⁵⁵ and saline solution¹⁶ into the connective tissue around the TMJ¹⁸ , while arthrocentesis injects saline solution into the joint space, combined or not with hyaluronic acid, platelet-rich fibrins, PRP⁵⁶,⁵⁷ . In patients with intra-articular TMJ alterations that don't respond to conservative methods, PRD can be a viable alternative before the indication of more invasive surgical treatments¹⁸,⁵⁸,⁵⁹ .

Some authors indicate that no concentration of dextrose is superior in TMJ PR, all being effective in improving hypermobility symptoms. However, PR with 10% dextrose may be sufficient to treat this condition¹⁷ . PR can reduce the need for drugs in TMD patients, improving quality of life.

Studies show that PRD has an analgesic and functional effect, reducing the use of analgesics and anti-inflammatory drugs. Its mechanism is based on inducing controlled inflammation, promoting tissue repair and ligament strengthening, reducing hypermobility and pain. In addition, by minimizing the adverse effects of non-steroidal anti-inflammatory drugs, such as gastrointestinal and cardiovascular complications, PRD is a safe, minimally invasive and long-lasting option¹⁷,²¹ . Nevertheless, it's important that each case is assessed individually to ensure the appropriate indication.

One of the main challenges of PR is the need for multiple injection cycles to achieve satisfactory results, which prolongs treatment and requires greater patient commitment. Accuracy can be affected by anatomical variations and the absence of ultrasound, but proper training and the use of imaging techniques minimize these limitations, making PRD a viable option for TMD¹⁷,⁶⁰-⁶² . Faced with the challenges of PR in TMD, it is recommended to start with an injection at a single strategic point, such as the posterior superior ligament of the retrodiscal tissue, to assess the therapeutic response and minimize the invasive aspect of the treatment. If necessary, infiltration can be extended to other anatomical points¹⁰ . Further research is essential to standardize protocols, including the minimum effective dose, the ideal interval between applications and the number of cycles required. This will make it possible to individualize treatment, optimize results and consolidate PR as an evidence-based option in the management of TMD.

CONCLUSION

PRD was effective in managing TMD, especially myofascial pain, hypermobility, subluxation and disc displacement with reduction. It is a minimally invasive alternative which promotes tissue regeneration and TMJ stabilization with good results. Nevertheless, further studies are needed to standardize protocols and better define indication. Careful patient selection and evaluation of contraindications are essential to optimize results and reduce risks.

• Sponsoring sources:
  none.

References

• ¹ Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, List T, Svensson P, Gonzalez Y, Lobbezoo F, Michelotti A, Brooks SL, Ceusters W, Drangsholt M, Ettlin D, Gaul C, Goldberg LJ, Haythornthwaite JA, Hollender L, Jensen R, John MT, De Laat A, de Leeuw R, Maixner W, van der Meulen M, Murray GM, Nixdorf DR, Palla S, Petersson A, Pionchon P, Smith B, Visscher CM, Zakrzewska J, Dworkin SF, International RDC/TMD Consortium Network, International association for Dental Research, Orofacial Pain Special Interest Group, International Association for the Study of Pain. International RDC/TMD Consortium Network, International association for Dental Research; Orofacial Pain Special Interest Group, International Association for the Study of Pain. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†. J Oral Facial Pain Headache. 2014;28(1):6-27. http://doi.org/10.11607/jop.1151 PMid:24482784.
  » http://doi.org/10.11607/jop.1151
• ² Fernandes G, Gonçalves DAG, Conti P. Musculoskeletal Disorders. Dent Clin North Am. 2018;62(4):553-64. http://doi.org/10.1016/j.cden.2018.05.004 PMid:30189982.
  » http://doi.org/10.1016/j.cden.2018.05.004
• ³ Liu F, Steinkeler A. Epidemiology, diagnosis, and treatment of temporomandibular disorders. Dent Clin North Am. 2013;57(3):465-79. http://doi.org/10.1016/j.cden.2013.04.006 PMid:23809304.
  » http://doi.org/10.1016/j.cden.2013.04.006
• ⁴ Dimitroulis G. Management of temporomandibular joint disorders: a surgeon’s perspective. Aust Dent J. 2018;63(Suppl 1):S79-90. http://doi.org/10.1111/adj.12593 PMid:29574810.
  » http://doi.org/10.1111/adj.12593
• ⁵ Hakala RV. Prolotherapy (proliferationtherapy) in the treatment of TMD. Cranio. 2005;23(4):283-8. http://doi.org/10.1179/crn.2005.040 PMid:16353469.
  » http://doi.org/10.1179/crn.2005.040
• ⁶ Goswami A. Prolotherapy. J Pain Palliat Care Pharmacother. 2012;26(4):376-8. http://doi.org/10.3109/15360288.2012.734900 PMid:23216178.
  » http://doi.org/10.3109/15360288.2012.734900
• ⁷ Hackett GS, Hemwall G, Montgomery G. Ligament and tendon relaxation treated by prolotherapy. 5th ed. Oak Park: Gustav A. Hemwall MD; 1993.
• ⁸ Hackett GS. Ligament and tendon relaxation treated by prolotherapy. Springfield: Charles C Thomas; 1956.
• ⁹ Andre A, Kang J, Dym H. Pharmacologic treatment for temporomandibular and temporomandibular joint disorders. Oral Maxillofac Surg Clin North Am. 2022;34(1):49-59. http://doi.org/10.1016/j.coms.2021.08.001 PMid:34598856.
  » http://doi.org/10.1016/j.coms.2021.08.001
• ¹⁰ Majumdar SK, Krishna S, Chatterjee A, Chakraborty R, Ansari N. Single injection technique prolotherapy for hypermobility disorders of TMJ using 25% dextrose: a clinical study. J Maxillofac Oral Surg. 2017;16(2):226-30. http://doi.org/10.1007/s12663-016-0944-0 PMid:28439165.
  » http://doi.org/10.1007/s12663-016-0944-0
• ¹¹ Ravikumar C, Sasikala B, Krishnakumar Raja VB, Elavenil P. Evaluation of the efficacy of autologous conditioned serum versus dextrose prolotherapy in internal derangement of the TMJ - A pilot study. J Craniomaxillofac Surg. 2024;52(4):477-83. http://doi.org/10.1016/j.jcms.2024.01.025 PMid:38368212.
  » http://doi.org/10.1016/j.jcms.2024.01.025
• ¹² Kim MY, Na YM, Moon JH. Comparison on treatment effects of dextrose water, saline, and lidocaine for trigger point injections. J Korean Acad Rehabil Med. 1997;21:967-73.
• ¹³ Hakala RV, Lederman KM. The use of prolotherapy for temporomandibular joint dysfunction. J of Prolotherapy. 2010;2(3):439-46.
• ¹⁴ Gibaly A, Abdelmoiz M, Alghandour AN. Evaluation of the effect of dextrose prolotherapy versus deep dry needling therapy for the treatment of temporomandibular joint anterior disc displacement with reduction: (a randomized controlled trial). Clin Oral Investig. 2024;28(9):475. http://doi.org/10.1007/s00784-024-05830-z PMid:39115583.
  » http://doi.org/10.1007/s00784-024-05830-z
• ¹⁵ Zhou H, Hu K, Ding Y. Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation. Br J Oral Maxillofac Surg. 2014;52(1):63-6. http://doi.org/10.1016/j.bjoms.2013.08.018 PMid:24064304.
  » http://doi.org/10.1016/j.bjoms.2013.08.018
• ¹⁶ Cömert Kiliç S, Güngörmüş M. Is dextrose prolotherapy superior to placebo for the treatment of temporomandibular joint hypermobility? A randomized clinical trial. Int J Oral Maxillofac Surg. 2016;45(7):813-9. http://doi.org/10.1016/j.ijom.2016.01.006 PMid:26846795.
  » http://doi.org/10.1016/j.ijom.2016.01.006
• ¹⁷ Mustafa R, Güngörmüş M, Mollaoğlu N. Evaluation of the efficacy of different concentrations of dextrose prolotherapy in temporomandibular joint hypermobility treatment. J Craniofac Surg. 2018;29(5):e461-5. http://doi.org/10.1097/SCS.0000000000004480 PMid:29533255.
  » http://doi.org/10.1097/SCS.0000000000004480
• ¹⁸ Lee W. Prolotherapy of the temporomandibular joint is denoted as a new health technology in Korea. J Korean Assoc Oral Maxillofac Surg. 2023;49(2):59-60. http://doi.org/10.5125/jkaoms.2023.49.2.59 PMid:37114442.
  » http://doi.org/10.5125/jkaoms.2023.49.2.59
• ¹⁹ Cömert Kiliç S, Kiliç N, Güngörmüş M. Botulinum toxin versus dextrose prolotherapy: which is more effective for temporomandibular joint subluxation? A Randomized Clinical Trial. J Oral Maxillofac Surg. 2023;81(4):389-95. http://doi.org/10.1016/j.joms.2022.12.023 PMid:36693543.
  » http://doi.org/10.1016/j.joms.2022.12.023
• ²⁰ Singh V, Trescot A, Nishio I. Injections for chronic pain. Phys Med Rehabil Clin N Am. 2015;26(2):249-61. http://doi.org/10.1016/j.pmr.2015.01.004 PMid:25952063.
  » http://doi.org/10.1016/j.pmr.2015.01.004
• ²¹ Refai H, Altahhan O, Elsharkawy R. The efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: a preliminary prospective, randomized, double-blind, placebo controlled clinical trial. J Oral Maxillofac Surg. 2011;69(12):2962-70. http://doi.org/10.1016/j.joms.2011.02.128 PMid:21757278.
  » http://doi.org/10.1016/j.joms.2011.02.128
• ²² Grossmann E, Poluha RL. Double-puncture versus single-puncture arthrocentesis: a randomized controlled trial with 3 years of follow-up. J Oral Facial Pain Headache. 2022;36(2):141-6. http://doi.org/10.11607/ofph.3074 PMid:35943324.
  » http://doi.org/10.11607/ofph.3074
• ²³ Grossmann E, Poluha RL. b Comparative study of arthrocentesis with concentric-needle cannula with classic concentric needle: a randomized single-blind controlled clinical trial. J Craniomaxillofac Surg. 2024;52(7):850-4. http://doi.org/10.1016/j.jcms.2024.04.009 PMid:38724289.
  » http://doi.org/10.1016/j.jcms.2024.04.009
• ²⁴ Grossmann E, Poluha RL. Comparison between TMJ arthrocentesis techniques with different needle positions: a randomized single-blind controlled clinical trial. J Craniomaxillofac Surg. 2021;49(5):368-72. http://doi.org/10.1016/j.jcms.2021.02.011 PMid:33642116.
  » http://doi.org/10.1016/j.jcms.2021.02.011
• ²⁵ Grossmann E, Poluha RL. The benefits of performing temporomandibular joint arthrocentesis with catheters and a vacuum pump: a randomized control trial. J Craniomaxillofac Surg. 2024;52(3):369-73. http://doi.org/10.1016/j.jcms.2024.01.020 PMid:38253472.
  » http://doi.org/10.1016/j.jcms.2024.01.020
• ²⁶ Priyadarshini S, Gnanam A, Sasikala B, Elavenil P, Raja Sethupathy Cheeman S, Mrunalini R, Krishna Kumar Raja VB. Evaluation of prolotherapy in comparison with occlusal splints in treating internal derangement of the temporomandibular joint - A randomized controlled trial. J Craniomaxillofac Surg. 2021;49(1):24-8. http://doi.org/10.1016/j.jcms.2020.11.004 PMid:33279397.
  » http://doi.org/10.1016/j.jcms.2020.11.004
• ²⁷ Renapurkar SK, Laskin DM. Injectable agents versus surgery for recurrent temporomandibular joint dislocation. Oral Maxillofac Surg Clin North Am. 2018;30(3):343-9. http://doi.org/10.1016/j.coms.2018.04.009 PMid:29866448.
  » http://doi.org/10.1016/j.coms.2018.04.009
• ²⁸ Prechel U, Ottl P, Ahlers OM, Neff A. The treatment of temporomandibular joint dislocation. Dtsch Arztebl Int. 2018;115(5):59-64. PMid:29439762.
• ²⁹ Vingender S, Dőri F, Schmidt P, Hermann P, Vaszilkó MT. Evaluation of the efficiency of hyaluronic acid, PRP and I-PRF intra-articular injections in the treatment of internal derangement of the temporomandibular joint: a prospective study. J Craniomaxillofac Surg. 2023;51(1):1-6. http://doi.org/10.1016/j.jcms.2023.01.017 PMid:36740515.
  » http://doi.org/10.1016/j.jcms.2023.01.017
• ³⁰ Al-Moraissi EA, Wolford LM, Ellis E 3rd, Neff A. The hierarchy of different treatments for arthrogenous temporomandibular disorders: a network meta-analysis of randomized clinical trials. J Craniomaxillofac Surg. 2020;48(1):9-23. http://doi.org/10.1016/j.jcms.2019.10.004 PMid:31870713.
  » http://doi.org/10.1016/j.jcms.2019.10.004
• ³¹ Poluha RL, Canales GT, Costa YM, Grossmann E, Bonjardim LR, Conti PCR. Temporomandibular joint disc displacement with reduction: a review of mechanisms and clinical presentation. J Appl Oral Sci. 2019;27:e2019er001. http://doi.org/10.1590/1678-7757-2018-0433. PMid:30810641.
• ³² Nitzan DW, Naaman HL. Athrocentesis: what, when, and why? Atlas Oral Maxillofac Surg Clin North Am. 2022;30(2):137-45. http://doi.org/10.1016/j.cxom.2022.06.008 PMid:36116872.
  » http://doi.org/10.1016/j.cxom.2022.06.008
• ³³ George MD, Lee RJ, Kryscio RJ, Kaplan JD. Safety and efficacy of prolotherapy in the management of temporomandibular joint disorders. J Maxillofac Oral Surg. 2015;14(1):49-56.
• ³⁴ Haggag MA, Al-Belasy FA, Said Ahmed WM. Dextrose prolotherapy for pain and dysfunction of the TMJ reducible disc displacement: A randomized, double-blind clinical study. J Craniomaxillofac Surg. 2022;50(5):426-31. http://doi.org/10.1016/j.jcms.2022.02.009 PMid:35501215.
  » http://doi.org/10.1016/j.jcms.2022.02.009
• ³⁵ Haggag MH, El-Saeed TA, Shabana TM. Efficacy of dextrose prolotherapy compared with lidocaine injection in temporomandibular joint disorders: a randomized clinical trial. J Oral Maxillofac Surg. 2017;75(5):946-52.
• ³⁶ Haggag MH, El-Saeed TA, Shabana TM. Prolotherapy: a new approach for temporomandibular joint dysfunction. Egypt Dent J. 2020;66(3):2735-42.
• ³⁷ Haggag MH, El-Saeed TA, Shabana TM. Long-term outcomes of prolotherapy in temporomandibular joint dysfunction. J Oral Maxillofac Surg. 2017;75(6):954-60.
• ³⁸ Hauser RA, Hauser MA, Baird NM. Evidence-based use of dextrose prolotherapy for musculoskeletal pain: a review. Clin Med Insights Arthritis Musculoskelet Disord. 2016;9:139-59. http://doi.org/10.4137/CMAMD.S39160 PMid:27429562.
  » http://doi.org/10.4137/CMAMD.S39160
• ³⁹ Hauser RA, Hauser MA. Dextrose prolotherapy for degenerative joint disease of the temporomandibular joint: a prospective pilot study. J Prolotherapy. 2009;1(3):167-75.
• ⁴⁰ Hsu C, Vu K, Borg-Stein J. Prolotherapy: a narrative review of mechanisms, techniques, and protocols, and evidence for common musculoskeletal conditions. Phys Med Rehabil Clin N Am. 2023;34(1):165-80. http://doi.org/10.1016/j.pmr.2022.08.011 PMid:36410881.
  » http://doi.org/10.1016/j.pmr.2022.08.011
• ⁴¹ Dasukil S, Shetty SK, Arora G, Degala S. Efficacy of prolotherapy in temporomandibular joint disorders: an exploratory study. J Maxillofac Oral Surg. 2021;20(1):115-20. http://doi.org/10.1007/s12663-020-01328-9 PMid:33584052.
  » http://doi.org/10.1007/s12663-020-01328-9
• ⁴² ELwerfelli AM, Kalil AEF, Abdullah NS. Clinical evaluation of dextrose prolotherapy for management of temporomandibular joint disorder. Alex Dent J. 2019;4(3):1-7. http://doi.org/10.21608/adjalexu.2019.63548
  » http://doi.org/10.21608/adjalexu.2019.63548
• ⁴³ Mohammed MM, Abdelkarim FM. Prolotherapy compared to corticosteroid in the treatment of temporomandibular joint pain: a clinical trial. Pain Res Manag. 2019;6:123-31.
• ⁴⁴ Zarate P, Martinez JE, Padilla NR. Prolotherapy for temporomandibular joint hypermobility: a clinical update. J Oral Rehabil. 2023;50(7):792-8.
• ⁴⁵ Fouda AA. Change of site of intra-articular injection of hypertonic dextrose resulted in different effects of treatment. Br J Oral Maxillofac Surg. 2018;56(8):715-8. http://doi.org/10.1016/j.bjoms.2018.07.022 PMid:30107954.
  » http://doi.org/10.1016/j.bjoms.2018.07.022
• ⁴⁶ Zarate P, Martinez JE, Padilla NR. Prolotherapy in temporomandibular joint hypermobility: a review of the literature. J Prolotherapy. 2010;2(2):448-52.
• ⁴⁷ Sit RW, Chung VC, Reeves KD, Rabago DP. The effectiveness of prolotherapy for temporomandibular joint disorders: A systematic review and meta-analysis. Pain Physician. 2022;25(3):361-70.
• ⁴⁸ Rahimzadeh P, Imani F, Faiz SH, Pourhoseingholi MA. Dextrose prolotherapy vs local anesthetic injection for the treatment of temporomandibular joint hypermobility: a randomized clinical trial. Pain Pract. 2014;14(7):641-5.
• ⁴⁹ Jacob SM, Bandyopadhyay TK, Chattopadhyay PK, Parihar VS. Efficacy of platelet-rich plasma versus hyaluronic acid following arthrocentesis for temporomandibular joint disc disorders: a randomized controlled trial. J Maxillofac Oral Surg. 2022;21(4):1199-204. http://doi.org/10.1007/s12663-021-01519-y PMid:36896087.
  » http://doi.org/10.1007/s12663-021-01519-y
• ⁵⁰ Rossini R, Grossmann E, Poluha RL, Setogutti ÊT, Dos Santos MF. Double-needle arthrocentesis with viscosupplementation in patients with temporomandibular joint disc displacement without reduction. Clinics (São Paulo). 2021;76:e2840. http://doi.org/10.6061/clinics/2021/e2840 PMid:33909828.
  » http://doi.org/10.6061/clinics/2021/e2840
• ⁵¹ Wang R, Bi R, Liu Y, Cao P, Abotaleb B, Zhu S. Morphological changes of TMJ disc in surgically treated ADDwoR patients: a retrospective study. BMC Oral Health. 2022;22(1):432. http://doi.org/10.1186/s12903-022-02469-8 PMid:36182911.
  » http://doi.org/10.1186/s12903-022-02469-8
• ⁵² Wroclawski C, Mediratta JK, Fillmore WJ. Recent Advances in Temporomandibular Joint Surgery. Medicina (Kaunas). 2023;59(8):1409. http://doi.org/10.3390/medicina59081409 PMid:37629699.
  » http://doi.org/10.3390/medicina59081409
• ⁵³ De Nordenflycht D, Ayala A, Orellana L, Tesch RS. Intra-articular injections in the TMJ inferior joint space: A scoping review. J Oral Rehabil. 2023;50(11):1316-29. http://doi.org/10.1111/joor.13542 PMid:37323068.
  » http://doi.org/10.1111/joor.13542
• ⁵⁴ Ling LP, Lua JL, Tang JS. The effect of dextrose prolotherapy on temporomandibular joint hypermobility: A prospective randomized clinical trial. J Oral Maxillofac Surg. 2013;71(12):2177-84.
• ⁵⁵ Zarate P, Martinez JE, Padilla NR. Prolotherapy versus lidocaine injection for temporomandibular joint disorders: a randomized controlled trial. J Oral Rehabil. 2022;49(6):726-32.
• ⁵⁶ Bhargava D, Sivakumar B, Bhargava PG. A Comparative Preliminary Randomized Clinical Study to Evaluate Heavy Bupivacaine Dextrose Prolotherapy (HDP) and Autologous Blood Injection (ABI) for Symptomatic Temporomandibular Joint Hypermobility Disorder. J Maxillofac Oral Surg. 2023;22(1):110-8. http://doi.org/10.1007/s12663-022-01738-x PMid:36703672.
  » http://doi.org/10.1007/s12663-022-01738-x
• ⁵⁷ Long X, Chen G, Cheng AH, Cheng Y, Deng M, Cai H, Meng Q. A randomized controlled trial of superior and inferior temporomandibular joint space injection with hyaluronic acid in treatment of anterior disc displacement without reduction. J Oral Maxillofac Surg. 2009;67(2):357-61. http://doi.org/10.1016/j.joms.2008.09.014 PMid:19138610.
  » http://doi.org/10.1016/j.joms.2008.09.014
• ⁵⁸ Reeves KD, Sit RW, Rabago DP. Prolotherapy: a non-surgical option for managing temporomandibular joint disorders. Pain Pract. 2021;21(2):123-32.
• ⁵⁹ Tocaciu S, McCullough MJ, Dimitroulis G. Surgical management of recurrent TMJ dislocation-a systematic review. Oral Maxillofac Surg. 2019;23(1):35-45. http://doi.org/10.1007/s10006-019-00746-5 PMid:30729355.
  » http://doi.org/10.1007/s10006-019-00746-5
• ⁶⁰ Rabago D, Best TM, Beamsley M, Patterson J. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sport Med. 2005;15(5):376-80. http://doi.org/10.1097/01.jsm.0000173268.05318.a4 PMid:16162983.
  » http://doi.org/10.1097/01.jsm.0000173268.05318.a4
• ⁶¹ Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med. 2003;9(3):58-62. PMid:12776476.
• ⁶² Sit RW, Reeves KD, Zhong CC, Wong CHL, Wang B, Chung VC, Wong SY, Rabago D. Efficacy of hypertonic dextrose injection (prolotherapy) in temporomandibular joint dysfunction: a systematic review and meta-analysis. Sci Rep. 2021;11(1):14638. http://doi.org/10.1038/s41598-021-94119-2 PMid:34282199.
  » http://doi.org/10.1038/s41598-021-94119-2

Edited by

• Associate editor in charge:
  Irimar de Paula Posso https://orcid.org/0000-0003-0337-2531

Publication Dates

• Publication in this collection
  02 May 2025
• Date of issue
  2025

History

• Received
  12 Nov 2024
• Accepted
  25 Feb 2025