Role of Photobiomodulation Therapy in Modulating Oxidative Stress in Temporomandibular Disorders. A Systematic Review and Meta-Analysis of Human Randomised Controlled Trials

Abstract

This systematic review and meta-analysis (PROSPERO registration; ref CRD 42020198921) aimed to govern photobiomodulation therapy (PBMT) efficacy in temporomandibular disorder (TMD). PRISMA guidelines and Cochrane Collaboration recommendations were followed. Differences in pain reduction assessment by qualitative measurement with visual analogue scale pain (VAS), pressure threshold (PPT) and maximum mouth opening (MMO) were calculated with 95% confidence intervals and pooled in a random effects model with a subgroup analysis, evaluating the role of follow-up duration. Heterogeneity was analysed using Q and I² tests. Publication bias was assessed by visual examination of funnel plot symmetry. Qualitative analysis revealed 46% of the 44 included studies showed a high risk of bias. Meta-analysis on 32 out of 44 studies revealed statistically significant intergroup differences (SSID) for VAS (SMD = -0.55; 95% CI = -0.82 to -0.27; Z = 3.90 (p < 0.001)), PPT (SMD = -0.45; 95% CI = -0.89 to 0.00; Z = 1.97 (p = 0.05)) and MMO (SMD = -0.45; 95% CI = -0.89 to 0.00; Z = 1.97 (p = 0.05)), favouring PBMT compared to control treatment strategies. Sensitivity analysis revealed SSID (SMD = -0.53; 95% CI = -0.73 to -0.32; Z = 5.02 (p < 0.0001)) with low heterogeneity (Τ² = 0.02; χ² = 16.03 (p = 0.31); I² = 13%). Hence, this review, for first time, proposed suggested recommendations for PBMT protocols and methodology for future extensive TMD research.

Keywords: TMD standard care; light-emitting diodes; low-level laser therapy; orofacial pain; oxidative stress; photobiomodulation; randomised controlled trials; reactive oxygen species; synovial joint proinflammatory mediators; temporomandibular joint disorder.

Figure 1

Schematic representation of the proposed aetiopathology mechanism of TMD and PBM mechanism of action in TMD management. Abbreviations: IL: Interleukin; TNF-α & β: transforming necrosis factor-beta and alpha; ROS: reactive oxygen species; ATP: adenosine triphosphate; MMP-1,2,9: matrix metalloproteinases-1,2,9; VEGF: vascular endothelial growth factor; HA: hyaluronic acid. All the abbreviations in this table are listed in Supplementary File S2.

Figure 2

PRISMA flow-chart of selected criteria for the included articles [37].

Figure 3

Risk of Bias assessment summary of the included studies based on the consensual answers of two individual assessors (R.H. and S.D.)

Figure 4

Risk of Bias assessment graph of the included studies expressed as percentages based on the consensual answers of two individual assessors (R.H. and S.D.).

Figure 5

Forest plot for primary outcome pain assessment (VAS score) from baseline up to the final follow-up timepoint.

Figure 6

Forest plot for secondary outcome quantitative pain reduction assessment (PPT) from baseline up to the final follow-up timepoint.

Figure 7

Forest plot for secondary outcome functionality improvement (MMO) from baseline up to the final follow-up timepoint.

Figure 8

Forest plot with sub-group analysis for primary outcome qualitative pain reduction assessment (VAS score) from baseline up to the final follow-up timepoint.

Figure 9

Sensitivity analysis for primary outcome qualitative pain reduction assessment (VAS score) from baseline up to the final follow-up timepoint.

Figure 10

Funnel plot summary for primary outcome qualitative pain reduction assessment (PPT) from baseline up to the final follow-up timepoint.

Figure 11

Funnel plot summary for secondary outcome quantitative pain reduction assessment (VAS score) from baseline up to the final follow-up timepoint.

Figure 12

Funnel plot summary for secondary functionality improvement (MMO) from baseline up to the final follow-up timepoint.

Figure 13

Schematic representation of the proposed suggested number and allocations of the trigger points for PBM irradiation in TMD management. They are based on evidence derived from the literature and expert opinion and are intended only to provide clinical guidance and serve as a starting point for extensive research. The blue circle represents the trigger points’ allocations and their number.