Recent advances in the understanding of the aetiology and therapeutic strategies in burning mouth syndrome: Focus on the actions of cannabinoids

Abstract

Burning mouth syndrome (BMS) is a neuropathic pain disorder associated with a burning sensation on oral mucosal surfaces with frequently reported xerostomia, dysgeusia and tingling or paraesthetic sensations. However, patients present no clinically evident causative lesions. The poor classification of the disorder has resulted in a diagnostic challenge, particularly for the clinician/dentist evaluating these individuals. Major research developments have been made in the BMS field in recent years to address this concern, principally in terms of the pathophysiological mechanisms underlying the disorder, in addition to therapeutic advancements. For the purpose of this review, an update on the pathophysiological mechanisms will be discussed from a neuropathic, immunological, hormonal and psychological perspective. This review will also focus on the many therapeutic strategies that have been explored for BMS, including antidepressants/antipsychotics, non‐steroidal anti‐inflammatories, hormone replacement therapies, phytotherapeutic compounds and non‐pharmacological interventions, overall highlighting the lack of controlled clinical studies to support the effectiveness of such therapeutic avenues. Particular focus is given to the cannabinoid system and the potential of cannabis‐based therapeutics in managing BMS patients.

Burning Fog: Cognitive Impairment in Burning Mouth Syndrome

“…Patients affected by NCP are considered to be at high risk to develop a cognitive decline, especially in the domains of attention, working memory, and executive functions (Moriarty et al, 2011;Moriarty and Finn, 2014), which leads to the poor quality of life, difficulty in adherence to medications, increasing the risk of mortality, and health resource utilization (O'Connor, 2009;Colloca et al, 2017). Burning mouth syndrome is a complex chronic orofacial pain disorder frequently associated with several psychiatric comorbidities such as anxiety, depression, and sleep disturbances (Kim et al, 2020;Pereira et al, 2020) while CI have never been evaluated in a complete way. Only one study is found in the literature by Kim et al (2020), in an observational but a retrospective study, suggested that patients with BMS were not associated with an increase in the incidence of dementia and Parkinson's disease based on the diagnosis performed in ∼10 years by physicians, moreover, they could not assess whether the development of both conditions may be the consequence or were involved in the onset of BMS (Kim et al, 2020).…”

“…Burning mouth syndrome is a complex chronic orofacial pain disorder frequently associated with several psychiatric comorbidities such as anxiety, depression, and sleep disturbances (Kim et al, 2020 ; Pereira et al, 2020 ) while CI have never been evaluated in a complete way. Only one study is found in the literature by Kim et al ( 2020 ), in an observational but a retrospective study, suggested that patients with BMS were not associated with an increase in the incidence of dementia and Parkinson's disease based on the diagnosis performed in ~10 years by physicians, moreover, they could not assess whether the development of both conditions may be the consequence or were involved in the onset of BMS (Kim et al, 2020 ).…”

“…Its pathogenesis remains debated, but it is reasonable to assume a multifactorial process, including psychological factors, central nervous system dysfunctioning, peripheral small fiber neuropathy (Yilmaz et al, 2007 ; Cazzato and Lauria, 2017 ), and inflammatory factors (Barry et al, 2018 ; Pereira et al, 2020 ). Neuroimaging has provided the evidence of structural and functional brain changes in BMS and in other neuropathic chronic pain (NCP) conditions, which are also commonly reported in neurodegenerative diseases such as Alzheimer's disease (AD) (Tariq et al, 2018 ) and vascular dementia (VD) (Martucci et al, 2014 ; Tu et al, 2020 ).…”

Cannabidiol modulation of oxidative stress and signalling

“…To date, a large body of data suggest that cannabinoids have therapeutic properties, alleviating symptoms of several CNS disorders. Indeed, cannabinoids can mitigate inflammation, reduce CNS spasticity, alleviate neuropathic pain, and a body of evidence indicates that cannabinoids provide neuroprotection following injury or inflammation in the CNS [ 99 , 100 ]. The most well-known cannabinoids are the phytocannabinoids synthesized by C. sativa , including THC, a euphoric component of the plant, in addition to CBD, cannabinol (CBN), cannabichromene (CBC) and cannabigerol (CBG), which are considered non-euphoric cannabinoids [ 101 ].…”

Vortioxetine versus other antidepressants in the treatment of burning mouth syndrome: An open‐label randomized trial

“…Currently, BMS is considered a multifactorial disease in which a central brain dysfunction (Hagelberg et al., 2003; Khan, Keaser, Meiller, & Seminowicz, 2014), a peripheral small fiber neuropathy (Lauria, 2005; Yilmaz et al., 2007), and psychological (Galli, Lodi, Sardella, & Vegni, 2017; Kim & Kho, 2018) and inflammatory factors ( Barry, O'Halloran, McKenna, McCreary, & Downer, 2018; Pereira et al., 2020) have been reported in its etiopathogenesis. In the last International Classification of Orofacial Pain, the authors captured the multidimensionality of the pain, highlighting the important role of social and psychological factors (the biopsychosocial model) in the assessment and management of every type of orofacial pain (ICOP, 2020).…”