Effect of Systemic Administration of Amitriptyline on Oral Microbes in Rats

Abstract

Background/Aim: Amitriptyline is a major tricyclic antidepressant that is also used to relieve chronic orofacial pain. Recently, alterations in gut flora due to various antidepressants have been demonstrated. However, it remains unknown how antidepressants affect the oral environment, including microbiota and innate immunity. The aim of this study was to investigate the effects of amitriptyline on oral microflora and antimicrobial peptides. Materials and Methods: Sprague-Dawley rats were intraperitoneally injected with amitriptyline for 2 weeks. The DNA extracted from the oral swabs were used to perform 16SrRNA sequencing to evaluate the oral microbiome. Quantitative RT-PCR was performed to evaluate the mRNA levels of antimicrobial peptides in the buccal tissues. Results: No significant differences in salivary flow rates were observed between the amitriptyline and control groups. Taxonomic analysis showed significant alterations in bacteria such as Corynebacterium, Rothia, and Porphyromonas due to amitriptyline administration. The beta diversity showed significant differences between the amitriptyline and control groups. Additionally, the predicted metagenome functions were significantly different between the two groups. The mRNA expression levels of antimicrobial peptides in the amitriptyline group were significantly higher as compared to controls. Conclusion: Systemic administration of amitriptyline may affect the oral environment, including oral microbes and innate immunity in the oral mucosa. Amitriptyline (AMI) is a tricyclic antidepressant (TCA) drug that increases monoamine levels in the synaptic region by blocking the reuptake of both serotonin and norepinephrine neurotransmitters (1). AMI relieves neuropathic pain, acts as an antidepressant, and has been applied to treat orofacial chronic pain, such as postherpetic neuralgia, trigeminal neuralgia, and burning mouth syndrome (2, 3). AMI has strong binding affinity for alpha-adrenergic, histamine (H1), and muscarinic (M1) receptors, leading to a wide range of side effects. Owing to AMI's anticholinergic effects, dry mouth is one of the most common side effects (4, 5).The relationship between the enteric nervous systems of the gut and central nervous system has been recently established as a "gut-brain axis" (6). This concept includes the alteration of gut flora caused by psychological stress, while changes in human behavior and appetite increase the sense of anxiety due to gut inflammation (6, 7). In addition, 2134