Therapeutic effect of adjunctive 940nm diode laser photobiomodulation with carbamazepine on pain , infrared orofacial thermography and oral health quality of life in Trigeminal Neuralgia: A randomized clinical trial

**Introduction:**Trigeminal neuralgia (TN) is a severe debilitating orofacial pain that greatly affects the oral function and quality of life of the affected individuals. It is usually managed first with anti- epileptics like Carbamazepine which is started with a dose 200 mg twice daily  and can be titrated to a maximum of 1200 mg daily. The full effect of Carbamazepine takes about 1-2 weeks to manifest. The side and adverse effects of Carbamazepine however are not tolerated by 40% of patients leading to discontinuation. The therapeutic effect of PBMT in TN acts by peripheral mechanisms other than carbamazepine and bring about their effect earlier and can therefore be used as adjuncts with Carbamazepine therapy especially in the earlier part of the treatment. The adjunctive therapeutic effect of PBMT in pain reduction can decrease the dosing regime and side/ adverse effects of Carbamazepine. It can also be used as adjunctive treatment in relapse of TN or exacerbation of pain during Carbamazepine therapy. The treatment outcomes of pain in TN are evaluated by subjective or patient reported outcome measures like VAS, BNI, Pain frequency etc. There are no objective parameters to evaluate the therapeutic effect of treatment while the impact of treatment on quality of life are usually evaluated on general health domain.

1. Aim

To assess the therapeutic efficacy of adjunctive photobiomodulation with 940nm diode laser with carbamazepine in the outcome dimension of pain (intensity, relief, frequency), infrared orofacial thermography and oral health quality of life in the management of Trigeminal Neuralgia.

Infrared thermography is used to determine Orofacial thermal asymmetry i.e. difference in orofacial skin temperature between affected area compared with contralateral normal area (≥ 0.3 ° C) in Trigeminal Neuralgia, an objective outcome measure.

2. Study objectives.

3. Primary objective:

To compare the effect of adjunctive photobiomodulation with 940nm diode laser against carbamazepine with sham diode laser photobiomodulation therapy in trigeminal neuralgia using VAS score for pain intensity measured over a period of time (at baseline and 2 days and 30 days post treatment).

2. Secondary objective:

3. To compare the pain intensity (VAS) at each session, pain relief (BNI score) and pain frequency at baseline, every follow up treatment session and  2 days and 30  days post treatment between the grouos - Carbamazepine with sham diode laser photo biomodulation therapy versus carbamazepine  with adjunctive laser photobiomodulation with 940nm diode laser in Trigeminal Neuralgia

4. To compare the infrared thermographic orofacial thermal asymmetry and impact of treatment on oral health quality of life (OHIP-14 score) at baseline and  2 days and 30  days post treatment between the groups - Carbamazepine with sham diode laser photo biomodulation therapy versus carbamazepine  with adjunctive laser photobiomodulation with 940nm diode laser in Trigeminal Neuralgia

Thermal asymmetry (difference in temperature between affected area compared with contralateral normal area ≥ 0.3 °C

1. Materials and Methods

2. Study Design:

A Randomized parallel arm-controlled trial, (outcome assessor and patient blinded)

Inclusion Criteria:

1. All new diagnosed cases of Trigeminal neuralgia as per ICHD-3 criteria reporting to the department of OMR, CDER and willing to participate in the study will be included.

2. Subjects diagnosed with TN experiencing relapse with a VAS score of  ≥5.

3. Subjects > 40 years of age.

4. Subjects willing to complete the treatment sessions.

Exclusion Criteria:

1. TN paitients on polypharmacotherapy
2. TN secondary to multiple sclerosis, tumor, CNS lesions, herpes zoster or any other causes other than oral surgery.
3. TN in solely V1 distribution and acute TN.
4. Past invasive treatment (MVD, alcohol block, cryosurgery, radiofrequency thermocoagulation, glycerol rhizolysis, gamma knife and stereotactic radiosurgery etc.).
5. Subjects with other orofacial pain like odontogenic/sinus/ ocular otologic pain/ infection, TMD’s, myofascial pain, atypical orofacial pain, Burning mouth syndrome, traumatic neuropathy, or other neurological, psychiatric, neuromuscular and sensory disorders.
6. Subjects with uncontrolled systemic diseases, with abnormal haemogram, liver function tests and renal function tests
7. . Subjects on anti-inflammatories, analgesics, anaesthetics or any other medication for neurological disorders
8. Subjects with current or past history of malignancy.
9. Alcoholics, drug addicts and patients with pacemaker.
10. Subjects with scars, tattoos, moles, traumatic, ulcerative, pathological skin lesion, open wounds, ulcers, or inflammation on facial skin in V2, V3 distribution sites to be exposed to Laser PBMT.
11. Subjects with bone marrow suppression, hypersensitivity to carbamazepine and tricyclic compounds
12. Pregnant and lactating females

Group A (n=118): Photo biomodulation therapy will be given extra orally along the nerve path of the division involved and intraorally over trigger points along with conventional first line pharmacotherapy regime – Carbamazepine 200 mg twice/day.

Group B: (n=118) Sham Photo biomodulation therapy (Placebo) (Use of laser handpiece with only red guide light and without using the foot pedal which activates the laser) (Intraoral and Extraoral) with conventional first line pharmacotherapy regime – Carbamazepine 200 mg twice/day.

Block Randomisation: Block randomisation with varying block size will be done using computer generated random numbers.with allocation ratio of 1:1

Allocation concealmentParticipants will be randomised using sequentially numbered, opaque sealed envelopes (SNOSE):

Study procedure

A structured questionnaire will be used to record past medical history, history of present illness and symptoms etc. followed by clinical / physical examination of the subjects to diagnose trigeminal neuralgia as per ICHD-3 criteria. Review of the past treatment records to rule out secondary or central causes of TN.

A diagram of a patient’s blood flow Description automatically generated

1. Statistical Analysis:

Data will be entered in an electronic data form and managed using Research Electronic Data Capture (REDcap) software. Analysis of baseline continuous variables will be compared between the two groups using unpaired T-test and categorical variables will be compared between the groups using chi squared test or fisher’s exact test. The primary outcome measure-VAS score will be compared between the two groups using repeated measures analysed using Intention to Treat and Per Protocol Analysis. Sub analysis for outcome parameters as per disease chronicity and sex will be done. Secondary continuous outcomes will be compared between the two groups using non-parametric - Friedman test.  Results will be presented as Difference in Means/Proportions with 95% confidence interval and p<0.05 will be considered statistically significant.

1. Expected outcomes:

We expect a significant improvement in pain intensity, relief, frequency, and oral health quality of life in patients receiving Laser PBMT compared to those solely on pharmacotherapy regime. Subjects with adjunctive PBMT can be maintained on lower pharmacotherapy with reduction in chance for drug adverse reactions and toxicity. We anticipate the presence of thermal asymmetry in TN patients, which could potentially normalize as pain may reduce over the course of treatment. This will indicate thermography can be used as an objective outcome measure for evaluating both pain levels and treatment effectiveness in management of TN.