|Year : 2022 | Volume
| Issue : 3 | Page : 279-288
Anti-inflammatory effects of photobiomodulation in the management of osteoarthritis of the temporomandibular joint: A systematic review of animal studies
Virginia Bautista1, Sandeep Talluri1, Olga A Korczeniewska2, Dimitrios Michelogiannakis3, Junad Khan1
1 Orofacial Pain and TMJ Disorders, Eastman Institute for Oral Health, University of Rochester, Rochester, NY, USA
2 Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Rutgers University, Newark, NJ, USA
3 Department of Orthodontics and Dentofacial Orthopedics, Eastman Institute for Oral Health, University of Rochester, Rochester, NY, USA
|Date of Submission||26-Aug-2021|
|Date of Acceptance||21-Nov-2021|
|Date of Web Publication||20-May-2022|
Dr. Junad Khan
Orofacial Pain and TMJ Disorders, Eastman Institute for Oral Health, 625 Elmwood Ave, Box 683, Rochester, NY 14642
Source of Support: None, Conflict of Interest: None
Aim: There is a controversy in regards to the efficacy of photobiomodulation (PB) in the management of osteoarthritis (OA) of the temporomandibular joint (TMJ). The aim of this study was to assess if PB induces anti-inflammatory effects for the management of OA of the TMJ.
Materials and Methods: The focused question was “Does PB induce anti-inflammatory effects for the management of OA of the TMJ?” Indexed database search was performed up to and including June 2020. Data regarding study design, study grouping, subjects, age, sex, OA induction method, outcome variables, and parameters regarding OA in TMJ were extracted.
Results: A total of 47 articles were initially identified through indexed databases and 6 experimental animal studies were included in the present review. Overall the risk of bias was high in two studies and moderate in four studies. A variety of results were evaluated after histopathological, biochemical, and radiographic analysis. After PB, there was a reduction in the articular disc thickness in the anterior, middle, and posterior regions, inflammation in the retrodiscal tissues was significantly reduced, and there was reduced expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, glycosaminoglycans and caspase-3 on biochemical analysis of the TMJ. The condyle showed the absence of inflammation after low-level laser therapy, and there was also a reduction of inflammatory infiltrate in the TMJ.
Conclusions: Within the limits of the present systematic review, it is concluded that PB is a potent therapeutic agent in the management of OA in TMJ.
Keywords: Inflammation, low-level laser therapy, osteoarthritis, photobiomodulation, temporomandibular joint
|How to cite this article:|
Bautista V, Talluri S, Korczeniewska OA, Michelogiannakis D, Khan J. Anti-inflammatory effects of photobiomodulation in the management of osteoarthritis of the temporomandibular joint: A systematic review of animal studies. Indian J Rheumatol 2022;17:279-88
|How to cite this URL:|
Bautista V, Talluri S, Korczeniewska OA, Michelogiannakis D, Khan J. Anti-inflammatory effects of photobiomodulation in the management of osteoarthritis of the temporomandibular joint: A systematic review of animal studies. Indian J Rheumatol [serial online] 2022 [cited 2022 Oct 3];17:279-88. Available from: https://www.indianjrheumatol.com/text.asp?2022/17/3/279/345615
| Introduction|| |
Osteoarthritis (OA) is the most frequent chronic musculoskeletal disorder and the leading cause of pain and disability of the musculoskeletal system., Moreover, the most distinctive feature in OA is the degeneration and loss of cartilage as well as synovial inflammation.,, Around 15% of the world's population is affected by OA., OA can take place at any age; nevertheless, individuals 65 years or older present an increased radiological evidence of degenerative changes consistent with OA compared to younger individuals., OA of the temporomandibular joint (TMJ) is a degenerative disease that consists of chronic degradation of the hard and soft tissues in and around the TMJ, and is the most common type of arthritis that affects the TMJ. According to the American Academy of Orofacial Pain, OA of the TMJ is classified into primary and secondary categories. Primary OA of the TMJ is characterized by the absence of any distinct local or systemic factors; whereas, secondary OA of the TMJ is associated with a previous traumatic event or disease.,,
A multidisciplinary approach is usually followed for the treatment of TMJ OA. Therapeutic interventions include behavioral therapy, soft diet, analgesics, and nonsteroidal anti-inflammatory drugs, physical therapy, use of occlusal splints, and acupuncture., However, a consensus related to a definite treatment protocol in relation to TMJ OA is yet to be reached. Low-level laser therapy (LLLT) or photobiomodulation (PB) has been used in the treatment of oral inflammatory conditions such as gingivitis, periodontitis, alveolar osteitis, and oral cancer.,,,,, However, results from animal studies investigating the effects of PB on OA-related conditions are controversial, with some studies showing anti-inflammatory effects of PB, while others did not find the beneficial effects of PB on healing. It has also been demonstrated that PB can partially restore cartilage defects under proper irradiance and irradiation. A limited number of clinical studies, with varying methodology have assessed the influence of LLLT or PB in the management of TMJ OA and have also conveyed controversial results.,,, To the authors' knowledge from pertinent indexed literature, there are no studies that have systematically reviewed the role of PB in the management of OA of the TMJ. Therefore, the aim of the present systematic review was to assess the anti-inflammatory effects of PB in the management of TMJ-related OA.
| Materials and Methods|| |
The focused question was “Does PB induce anti-inflammatory effects for the management of OA of the TMJ?”
The Population (P): animals with TMJ OA; Intervention (I): management of OA using PB; Control (C): management of OA using regimens other than PB or no treatment; Outcome measure (O): reduction in inflammation or related parameters (histopathological, biochemical and radiographic analysis) format was followed.
The inclusion criteria were: (a) original studies performed on animal models of TMJ OA, (b) prospective studies, (c) studies using PB externally over the TMJ for the management of TMJ OA, (d) studies with a control group, (e) studies that performed statistical analysis and (f) studies with outcome measures for the assessment of TMJ OA. Clinical studies, letters to the editor, case reports, case series, commentaries, historic reviews, and studies published in non-indexed databases were excluded.
Study selection and literature search protocol
Electronic database (PubMed, Cochrane Library, Medline, Scopus) searching of reference lists was performed up until June 2020. Titles and abstracts of potentially relevant studies were screened by two authors (VB and ST). The full texts of pertinent studies were retrieved and evaluated independently. Hand searching of the reference lists of relevant articles was also performed. Any disagreements between investigators were resolved via mutual discussion. The keywords TMJ, OA, LLLT, PB, inflammation was used as a search strategy. A meta-analysis was not performed due to the heterogeneity in the studies.
Screening methods, data extraction and risk of bias assessment
Two authors (VB, ST) independently reviewed the articles, and information was synthesized by tabulating the data according to (a) study design, (b) relevance of study characteristics pertaining to characteristics of laser, (c) relevance of study characteristics pertaining to the characters of inflammation and its evaluation and (d) study outcomes of LLLT of OA in animal specimens. SYRCLE's risk of bias tool for animal studies was used to assess qualitatively the included studies.
| Results|| |
An extensive search on several databases was performed according to the eligibility criteria. A total of 47 studies were initially identified. Twenty-six articles were identified through the PubMed database. Twenty-one articles were found through additional sources (Medline, Cochrane, Scopus). Twelve articles were duplicates and were removed. Twenty-nine were excluded after title and abstract screenings. As a result, 6 experimental animal studies were selected for full text reviewing and included in this review.,,,,, Five studies were performed in rats,,, and 1 study was performed in rabbits [Figure 1].
|Figure 1: Studies included for qualitative assessment based upon the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines|
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Characteristics of the studies
All studies were randomized controlled trials and used PB as an experimental group. The control groups included: (a) a noninduced OA group,,,,, (b) a nontreated OA-induced group [Table 1].,,
Study characteristics relevant to LLLT administration
All experimental studies used diode for the laser therapy. Four experimental studies,,, used a continuous wave mode of LLLT. One male rat study reported using pulsed mode laser therapy. The range of wavelength of the laser light was between 810 and 940 nm. The power output ranged from 0.2 W to 100 W. A laser probe diameter of 0.8 mm was reported only in one study with male rats. The spot size ranged from 300 μm to 0.116 cm2. The power density ranged from 0.259 W/cm2 to 1.02 W/cm2. The duration of laser application ranged between 12 s to 600 s [Table 2].
|Table 2: Study characteristics related to the application of laser therapy|
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Characteristics of inflammation induction
To measure the anti-inflammatory effects of LLLT the included studies,,,,, used cone-beam computed tomography (CBCT), histological analysis,,,,,, biochemical analysis,, zymography, and amount of feed animals consumed during 3 weeks. The induction of arthritis in the TMJ was initiated by injecting Complete Freund's Adjuvant/Freund's Complete Adjuvant in male rats,,,, monosodium iodoacetate in female rats and in rabbits [Table 3].
Characteristics of outcome of inflammation
The histopathological analysis reflected better collagen fibers organization in the articular disc and higher proteoglycans concentration in the disc and articular cartilage changes, in the experimental group. Other studies showed a thin layer of synovial membrane without any inflammation or fibrous tissue, number of cartilage inflammatory cells, cell layers, arthritis and cartilage thinning and fibrillation, along with increased subchondral trabecular bone density in the experimental group. One animal study showed that LLLT promoted smaller thickness of the articular disc in the anterior, middle, and posterior regions, indicating better arrangement and compaction of the collagen fibers network. Another study reflected a significant decrease in thickness of the articular disc middle area at 5 J/cm2 LLLT (middle region of the articular disc is responsible for supporting the greatest compressive loads during chewing efforts).,
Reduced inflammation characteristics upon histo and biochemical analysis included reduced total glycosaminoglycans concentration (measured anti-apoptotic activity), and reduced activity (active and latent) isoforms in both Matrix metalloproteinase (MMP)-9 and MMP-2. LLLT resulted in a decrease of MMP-2 latent activity and decreased latent and active MMP-9 (measured amount of feed)., LLLT significantly reduced the activity of active and latent isoforms of MMP-9 and MMP-2 after irradiating with different amount of doses. The same study reported a significant reduction in tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) concentration in LLLT groups. The grade of cartilage damage, number of inflammatory cells, number of cell layers, and arthritis in the experimental group improved compared to the controls. Caspase 3 was reduced in the irradiated group and the group that received injected corticosteroids. One study reported a significant reduction in TNF-α and IL-1β concentration in LLLT groups. The grade of cartilage damage, number of inflammatory cells, number of cell layers, and arthritis in the experimental group improved compared to the controls. Caspase 3 was reduced in the irradiated group and the group that received injected corticosteroids [Table 4] and [Table 5].
|Table 5: Study characteristics related to the evaluation of inflammation.|
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CBCT analysis reportedpositive results of minimal sclerosis at week 4 of LLLT. Regarding animal feed consumption, a study performed in male rats (during 3 weeks), there was a significant positive difference between healthy controls and groups treated with laser. There was also a significant positive difference between the nontreated group and the group treated with laser. There was a significant difference between groups treated with laser at different doses.
Risk of bias
SYRCLE risk of bias tool for animal studies was used to assess bias for the studies included in this review. Out of the 6 studies included,,,,, only 2, studies reported the method of sequence generation. All the 6 studies have similar baseline characteristics of the animals included in respective studies. All the 6 studies did not report allocation concealment. Only 3,, studies reported random housing and 3 other studies did not report it. Blinding of outcome assessors was done only in 1 study while other 5 included studies did not report it. All the 6 studies did not report random outcome assessment. All the 6 studies have reported both attrition and exclusions of animals involved in the study. All the 6 studies reported all the outcomes mentioned to include in the study [Table 6] and [Figure 2]. Overall, the risk of bias was high for 2 studies and moderate for 4 studies.
|Figure 2: The risk-of-bias of the included studies was assessed using the Systematic Review Centre for Laboratory Animal Experimentation tool|
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| Discussion|| |
OA affects millions of people worldwide and is the most common joint disorder in the United States. Therefore, new and effective treatments and preventive measures for OA are needed. The present review aimed to assess the impact of PB on reducing inflammatory processes of OA in the TMJ. An extensive search of several electronic bibliographic databases was performed resulting in 6 studies that were included and processed for data extraction.,,,,, This review focused on animal models of OA in TMJ because experimentally induced OA in animal models present similar mechanisms as in humans allowing for the investigation of the mechanisms contributing to the pathogenesis of TMJ OA. A variety of early results were found after histopathological and biochemical analysis, and results reported from radiographic exposure. After LLLT, studies reported reduced expression and activity of MMP-2 and MMP-9., It appears that PB abolishes the rise in MMP-9 and MMP-2 expression and gelatinolytic activity with a consequent reduction of inflammation. There was a moderate reduction of caspase-3, which is a chondrocyte apoptotic marker. Chondrocyte apoptosis in the early stages is an initiator of cartilage disintegration. LLLT dose of 5 J/cm2 promoted a reduction in thickness of the disc middle part in one study, whereas in another study there was reduction of morphological changes in the articular disc at a dose of 3 J/cm. Studies have demonstrated that the disc increases its thickness while adapting to biomechanical stress conditions. The middle region of the articular disc is responsible for supporting the greatest compressive loads during chewing. PB demonstrated to be effective in the treatment of induced TMJ arthritis at lower doses. Therefore, it is recommended to initiate the treatment of inflammatory disorders with lower doses.
Dexamethasone was used in an injected form to treat OA in the TMJs of the animals in one study. Another study administered systemic betamethasone. Corticosteroids bind to glucocorticoid receptors in the cytoplasm, regulating the transcription of certain genes to reduce the synthesis of pro-inflammatory cytokines. In a similar way, PB increases ATP production in the mitochondria and initiates the transcription of molecular factors initiating the synthesis of proteins that trigger cell repair and anti-inflammatory processes, and inhibiting the expression of cytokines involved in the inflammatory process.
CBCT performed in female rats showed great improvement in the erosion and the flattening in the articular surface of the condylar head in both of the treated groups, group treated with corticosteroids and group treated with laser irradiation. The accuracy of CBCT in detecting osseous changes is as high as 87%, which is desirable for the assessment of the osteophytes, erosion, condyle flattening, and sclerosis in the OA induced joints.
PB showed a significant reduction of cytokines (IL-1ß, IL-6),,, cells (macrophages and neutrophils), TNF-a, PGE2 and COX2, and reduction of cartilage degrading factors (matrix metalloproteinases, prostaglandin E, proteoglycans and Capsase 3), which indicate a reduction in the inflammatory process. The consistent histologic findings in all the included studies in this review suggest that LLLT may be associated with anti-inflammatory effects.
There was inconsistency in regards to the wavelength of the laser (which varied from 810 to 940 nm) energy and dose through the studies included. This is an important fact since the wavelength of the laser determines the depth of penetration. The effect of the laser determines how fast the energy is transferred to the tissue being treated and the more powerful the laser, the more joules are transferred to the tissue., The site of the laser treatment also determined its efficacy, considering that the light was directly applied to the skin on the TMJs of the animals.,,,,, Based on the findings in this review, it is complicated to establish the correct parameters of PB in the application in clinical trials. It has been suggested that increased frequency and time of exposure of light irradiation might lead to a better outcome. In conclusion, there is no definitive laser therapy protocol for the management of OA of the TMJ Another limitation in the studies included in this systematic review is that only one article reported the sample size calculation process. Considering this, the overall reported results should be interpreted with discretion. All the 6 studies included in this review reported all the outcomes mentioned to include in the study [Table 6] and [Figure 2]. Overall, the risk of bias was high for 2 studies and moderate for 4 studies.
| Conclusions|| |
Previous results from animal studies that investigated the effects of PB on OA-related conditions are controversial, with some studies showing anti-inflammatory effects of PB. The consistent histologic findings in all the included studies in this review suggest that PB may be associated with anti-inflammatory effects. Based on the animal models included in this review, the findings suggest that PB may be associated with anti-inflammatory effects. PB might have a potential role in the treatment of OA of the TMJ. Further experimental studies are needed to better understand and establish an adequate treatment protocol for TMJ OA patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]