The temporomandibular joint (TMJ) has unique characteristics, including the ability to move in three planes, its role as a load-bearing joint, and its direct relationship with the dentition. Therefore, orthopedic principles typically used for managing other acutely injured joints may not be applicable to the TMJ¹. The management of temporomandibular disorder (TMD) is gaining more attention in oral and maxillofacial surgery due to the increasing number of affected patients. In recent decades, the emergence of arthroscopy and arthrocentesis has significantly shifted the primary treatment approach for TMD from surgical to non-surgical, minimally invasive interventions. Primary conservative treatments include medications (nonsteroidal anti-inflammatory drugs [NSAIDs]) for anti-inflammation and pain control, occlusal splint therapy, and physiotherapy². If conservative treatment fails, surgical treatment is considered. Before performing open joint surgery, many clinicians attempt minimally invasive interventions such as botulinum toxin A (BTX) injections into the associated muscles, steroid or hyaluronic acid injections into the joint space, arthrocentesis, or arthroscopy. BTX muscle injections, which inhibit muscle hyperactivity, as well as superior joint injections and arthrocentesis, which lavage inflammatory substances in the joint cavity, are effective in correcting joint function and reducing pain³. However, the causes of TMD can also include inflammatory conditions and chronic pain of various structures such as the articular disc, retrodiscal tissue, TMJ-related ligaments and capsule, and tendons.

While various treatment options exist for TMD, one alternative gaining attention is prolotherapy, defined as “rehabilitating an incompetent structure such as a ligament or tendon by stimulating cellular proliferation”³. Prolotherapy, also known as “regeneration injection therapy,” is a non-surgical treatment method that aims to promote tissue repair and stimulate the body’s natural healing process⁴. It involves injecting a solution; often a mixture of dextrose, anesthetics, and saline; into the affected area. These injections aim to initiate a controlled inflammatory response, triggering the body to repair damaged tissues and strengthen the joint. When applied to the TMJ, prolotherapy targets the ligaments, tendons, and other connective tissues supporting the joint⁴. These structures can weaken or become damaged due to trauma, repetitive strain, or degenerative conditions, contributing to TMD symptoms. By stimulating the healing response, prolotherapy aims to strengthen the affected tissues, reduce pain, and improve joint function.

Although the exact cause of chronic TMD remains controversial, a dextrose solution greater than 10% can stimulate the proliferation of fibroblasts through both inflammatory and non-inflammatory mechanisms. This strengthens the TMJ-related connective tissue and significantly reduces pain levels in chronic TMD patients⁵. Dextrose is easily accessible, highly safe, and economical, decreasing the patient burden of TMJ prolotherapy. Thus, it may be beneficial for patients with early-stage TMD, those with refractory TMD who have had limited success with other treatments, and patients who are unwilling or unable to undergo TMJ surgery⁶. This study aims to evaluate the clinical efficacy of TMJ prolotherapy in chronic TMD patients who do not respond to conservative and interventional treatments.

This study included 19 patients (6 males, 13 females, average age 43 years, ranging from 18 to 74 years; Table 1), 11 of whom had parafunctional habits such as bruxism or clenching. Nine patients had popping or crepitus, three had clicking, and seven had no disc problems.(Fig. 1) Prolotherapy was administered up to three times. Thirteen patients (68.4%) received three prolotherapy sessions, two patients (10.5%) experienced symptom improvement after two sessions, and four patients (21.1%) experienced symptom improvement after one session.(Table 1)

In the cohort that underwent a series of three prolotherapy sessions, the initial mean TMJ discomfort value (NRS) was recorded at 5.7 (n=19). Among those who received all three sessions, the mean NRS score decreased progressively, with a mean score of 4.0 (n=19) after the first session, 2.5 (n=15) after the second session, and ultimately reaching a final mean score of 1.7 (n=13) upon completion.(Fig. 2) The mean maximum mouth opening (MMO) tended to decrease after the first prolotherapy session (34.5 mm to 33.5 mm) but gradually increased in subsequent sessions (34.8 mm to 38.8 mm).(Fig. 3) Overall, the satisfaction of TMD patients after prolotherapy treatment was positive.(Fig. 4) No serious complications were observed in any patients who received prolotherapy injections. Minor complications immediately following prolotherapy included mild pain at the injection sites and temporary ipsilateral facial nerve weakness, both of which subsided within 2 to 3 hours.

To investigate the effectiveness of prolotherapy in patients with bone-related symptoms such as arthritis, group A included 10 patients diagnosed with TMD type I, II, or III, and group B was nine patients with type IV.(Fig. 5) Regardless of the main cause of the symptoms, both pain scores and MMO improved after prolotherapy treatment, and both groups showed satisfactory outcomes.(Table 2)

We hypothesized that prolotherapy would be effective in reducing pain for chronic TMD patients who do not respond to conventional conservative treatments, including traditional therapies targeting the masticatory muscles and superior joint space. The clinical outcome was recorded using an NRS and relied on subjective patient opinion. Symptom relief was not specified according to type such as pain, limitation of opening, TMJ sound (clicking, crepitus, popping), or hypermobility of the jaw but was simplified as overall change in level of discomfort. The objective of this study was to substantiate the clinical efficacy of an alternative conservative treatment approach for patients with TMD-related chronic pain. Prolotherapy on the TMJ was effective in decreasing pain and discomfort in the TMJ area, and it also showed an additional effect in improving maximum opening regardless of main origin of symptoms.

Prolotherapy has been recognized since the 1930s for its efficacy in enhancing tendon, ligament, and joint stabilization⁴. Prolotherapy is currently being applied in the medical field across diverse anatomical joints, including the knee, finger and lumbar region, yielding favorable outcomes^11-13. The mechanism behind prolotherapy is not yet fully understood. The treatment first causes inflammation at the site of administration, initiating the inflammatory cascade¹⁴. Fibroblasts and endothelial cells mobilize toward the site of injury, promoting neovascularization and cellular proliferation and facilitating collagen deposition. Dextrose administration triggers the synthesis of crucial growth factors, including platelet-derived growth factor, transforming growth factor-beta, connective tissue growth factor, and epidermal growth factor, which are all essential for tissue repair¹⁵. This dynamic tissue remodeling process persists within tendon, ligament, and cartilage tissues over the course of several weeks to a few months. Hauser reported that TMJ prolotherapy could be recommended for patients with refractory TMDs or for those who achieved only limited success with other non-invasive treatments such as oral appliances or medication and for those who are unable or unwilling to receive open surgery¹⁶.

According to Mustafa et al.⁹, no significant differences in efficacy were shown for different concentrations of dextrose solution used in prolotherapy injections for TMD. Hakala and Ledermann¹⁷ asserted that “the precise concentration of dextrose is not critical as long as it is strongly hypertonic and causes adequate cell wall lysis to attract fibroblasts and begin the regenerative process.” Therefore, a 10% dextrose solution was used instead of a higher concentration as in other notable TMJ prolotherapy studies^8,10,17. As long as the solution is hypertonic, the prolotherapy treatment initiates the regenerative process by causing cell wall lysis and fibroblast activation¹⁷. However, it is important to avoid prescribing NSAIDs because they will prevent the controlled inflammatory response desired in prolotherapy treatment. Though dextrose solution is considered harmless, patients with uncontrolled or severe diabetes mellitus should be advised against hypertonic dextrose prolotherapy. Aspiration to prevent the inadvertent injection of the prolotherapy solution into blood vessels should always be emphasized.

TMJ prolotherapy is a relatively simple and safe injection procedure for any trained oral maxillofacial surgeon. However, given the various anatomical structures surrounding the TMJ, accurate injection of the dextrose solution into the targeted tissue and due consideration of anatomical variance should always be noted to achieve the most effective results⁷. In our experience, patients should be distinguished into two groups for effective prolotherapy treatment. First, patients with TMD-related trismus, muscle and joint pain, or TMJ clicking are categorized as group A prolotherapy. This category of TMD should be treated to limit masseter muscle function and regenerate the damaged ligament tissues attached to the TMJ disc. Therefore, these patients should receive injection into the retrodiscal attachment tissue, anterior disc attachment tissue, superior portion of the lateral capsule, and inferior portion of the lateral capsule. If symptoms persist, the origin of the masseter muscle located at the zygomatic arch can be an additional point for injection. Second, patients with bone-related problems are categorized as belonging to group B, which comprised patients with symptoms such as recurrent TMJ avulsion, hypermobility, or TMJ popping sounds. These patients should also receive injections at the insertion point of the stylomandibular ligament, which functions to limit excessive jaw protrusion. Further studies are needed to determine the most optimized prolotherapy injection points for the various TMD symptoms.

TMJ prolotherapy using hypertonic dextrose is a promising non-surgical treatment for chronic pain related with TMD, showing significant reductions in pain and improvements in joint function. Further research is needed to optimize injection points and tailor treatments to specific TMD symptoms for enhanced efficacy.