Salivary biomarkers to monitor orthodontic treatments biologically

Pain and discomfort are fundamental to human existence and occur commonly during orthodontic treatment - in the initial stages, mid-treatment, or post-orthodontic treatment. 

Many patients describe much more extended periods of pain and discomfort that are usually expected during the first 1 or 2 days of the orthodontic treatment. According to measurements at 4 hrs and 24 hrs, pain intensity generally increases with time but falls to normal levels after seven days of the orthodontic treatment. However, a study found that 25% of all investigated patients reported pain even after seven days of fixed appliance insertion. 

The current ‘gold-standard’ pain assessment tools rely on self-reporting, requiring individuals to process external information and communicate personal experiences through subjective pain scales and questionnaires, such as Visual Analog Scale (VAS), Graphic Rating (Graphical Representation) Scale, Numeric Rating Scale (NRS), Verbal Rating Scale (VRS), and McGill Pain Questionnaire (MPQ), etc. All these scales are patient-friendly as they are easily understandable by the patients. 

However, there are several drawbacks. Many patients cannot differentiate between pain and pressure. Also, special needs patients are generally unable to express themselves. 

How about making pain assessment objective instead of subjective?

If we could assess the biomarkers - the objective, quantifiable characteristics of biological processes, we could biologically monitor the orthodontic treatments and predict the outcomes of orthodontic forces. Then, the management of appliances could be based on individual tissue responses, and the effectiveness of the treatment could be improved. 

Objective pain assessment using salivary physiological biomarkers could become the new way for the clinician to diagnose and manage pain. Many salivary biomarkers are implicated in various types of pain. 

1. Several new isoforms for Nerve Growth Factor (NGF), Brain-derived Neurotropic Factor (BDNF), and Calcitonin gene-related peptide (CGRP) have been identified in saliva to develop new sensitive methods to detect and analyze markers related to pain. 
2. Calcitonin gene-related peptide (CGRP) and Brain-derived neurotrophic factor (BDNF) play a significant role in developing pain and hyperalgesia. CGRP and BDNF have been implicated in migraine and headaches based on increased saliva and plasma concentrations during active pain periods.

However, no validated objective pain markers exist in any field to date. The current study is the first of its kind that compared the efficacy of subjective pain scales VAS, VRS, NRS, and MPQ with salivary pain biomarkers BDNF and CGRP and their role in pain perception and nociception during the initial alignment stage of fixed orthodontic therapy in the Class I malocclusion with crowding subjects.

Results of the study revealed that BDNF levels showed statistically significant (p < 0.05) correlation with VAS, VRS, NRS at T3 and T4, and MPQ at T1 time intervals. Moreover, a timeline study of BDNF showed that it increased till the third day and started declining till day 7. 

This study shows that several sensitive salivary biomarkers are available to detect the biomechanical changes occurring during orthodontic tooth movement and pain during fixed orthodontic therapy. 

The following graphic illustration has been designed by Dr. Vaishnavi Yeleswarupu for easy understanding of this topic.

 

This study can be an eye-opener that provides valuable insight for future studies discovering many more objective pain markers which can differentiate between pain experiences in patients. 

Focussed research is warranted to help to analyze the sensitivity and reliability of these biomarkers, which in turn can lead to the development of chairside tests to assess the pain experienced by patients during orthodontic therapy, the advocation of new painless techniques to treat patients and, finally, the outcome of the fixed orthodontic therapy. 

Authors of the study

Dr. Sagar Bhat - Former Resident
Dr. Ameet V Revankar - Professor
Dr. Roopak D Naik - Professor & Head

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