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Treatment for RHL is often conservative and includes the consumption of soft foods, uids, and
analgesics for reducing symptoms [10]. In immune-compromised patients, and cases with severe
symptoms and frequent recurrence, antiviral drugs prescription (such as acyclovir)is common. Using

acyclovir few days before the onset of symptoms, accelerates the healing process [11]. On the other hand,
few other studies have shown that antiviral drugs have a limited effect on healing time and have no
effect on the recurrence rate [3, 12, 13]. However, evidence suggests that these drugs are associated with
several side effects and limitations, including short half-life, frequent usage, the risk of renal toxicity in
systemic administration, and HSV drug resistance.

Successful medical application of Photobiomodulation (PBM) has been widely reported across the
medical literature (e.g. in the treatment of musculoskeletal diseases, wound healing, skin burn treatment)

[14, 15]. Nowadays, much more is known about the effects of laser light on biochemical and cellular
function such as cellular metabolic activation [16], cell proliferation stimulation [17], anti-in ammatory
effect [16], microcirculation activation [18, 19], increased endorphin release and analgesic effects [19],

increased antioxidant activity [20], stimulation of erythropoiesis, vasodilatation [16] and re exogenic
effects on the functional activity of different organs and systems [17, 21, 22].

Few studies have reported PBM application as an alternative method for accelerated healing, reducing
symptoms and lowering the recurrence of RHL[23, 24]. Application of PBM on patients with recurrent
herpes simplex infection shown to decrease the recurrence frequency of herpes labialis [23]. Another
study found signi cant reduction of remission frequency in patients with recurrent herpes simplex
infection [24]. On contrary, laser irradiation in a murine model did not affect stablished herpes simplex

virus latency[25].

Despite available body of evidence, the question of usefulness of PBM on herpes simplex virus infections

treatment parameters (recurrence, symptoms severity, etc.) remains to be determined. In this study, we
aimed to evaluate the effect of PBM in the treatment of RHL.

Method and material

In this single-blind randomized clinical trial, 24 patients with RHL who were referred to the Alborz dental

clinic a liated with Urmia University of medical science were enrolled. Before starting the study, patients
were informed regarding the purpose of this study and provided signed consent to participate in this
study. The protocol was approved by the ethical committee of Urmia University of Medical Sciences
(IR.UMSU.REC.1400.048). The study protocol has also been registered and evaluated at Iranian Registry

of Clinical Trials (available at: https://www.irct.ir/; registration ID: IRCT20180224038840N2).

All the diagnosis and treatment processes were performed by an oral medicine specialist. All patients

diagnosed with herpes labialis lesions 0–48 hours before the study. Patients with acute systemic
diseases and other oral lesions were excluded. Participants were randomly divided into two groups (12
participants in acyclovir cream with PBM group, and 12 participants in acyclovir with placebo PBM)

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