Neuropharmacology of the Neuropsychiatric Symptoms of Dementia and Role of Pain: Essential Oil of Bergamot as a Novel Therapeutic Approach

Abstract

Aging of the population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioral and psychological syndromes known as neuropsychiatric symptoms of dementia remarkably reduce the quality of life. The cluster of symptoms includes anxiety, depression, wandering, delusions, hallucinations, misidentifications, agitation and aggression. The pathophysiology of these symptoms implicates all the neurotransmitter systems, with a pivotal role for the glutamatergic neurotransmission. Imbalanced glutamatergic and GABAergic neurotransmissions, over-activation of the extrasynaptic N-methyl-D-aspartate (NMDA) receptors and alterations of the latter have been linked to the development of neuropsychiatric symptoms experienced by almost the entire demented population. Drugs with efficacy and safety for prevention or long term treatment of these disorders are not available yet. Aromatherapy provides the best evidence for positive outcomes in the control of agitation, the most resistant symptom. Demented patients often cannot verbalize pain, resulting in unrelieved symptoms and contributing to agitation. Bergamot essential oil provides extensive preclinical evidence of analgesic properties. Incidentally, the essential oil of bergamot induces anxyolitic-like effects devoid of sedation, typical of benzodiazepines, with a noteworthy advantage for demented patients. These data, together with the reported safety profile, form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioral and psychological symptoms of dementia.

Opioids in Post-stroke Pain: A Systematic Review and Meta-Analysis

“…Indeed, all the included studies were quite old and dating prior to the 2009 CPSP redefinition (Klit et al, 2009), which made the differential diagnosis between CPSP and other types of post-stroke pain clearer and more reliable. Pain assessment represents an important issue in non-communicative patients, who can have difficulties to describe their pain, contributing to behavioral disturbances in some neurological conditions (Scuteri et al, 2017;Scuteri et al, 2018;Scuteri et al, 2019a;Scuteri et al, 2019b). Indeed, in the real-life clinical setting, the use of opioids in patients with post-stroke pain, who are not able to communicate is frequent, but the response to treatment is unclear (Schuster et al, 2020).…”

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

“…Apart from pain, dystonia is associated also to other, non-motor, symptoms, in particular psychiatric and behavioral symptoms [ 16 ]. These symptoms need accurate assessment, representing important predictors of health-related quality of life, as in neurodegenerative diseases such as Parkinson’s and Alzheimer disease [ 17 ]. Lines of transgenic mice overexpressing the human mutant (hMT) or the human wild-type (hWT) TA have been produced as models of DYT1 dystonia [ 18 ].…”

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance

“…Medicinal plant extracts, useful for different therapeutic purposes, e.g., aromatherapy in dementia [165][166][167][168], may influence the pharmacokinetics of co-administered drugs then inducing modifications in plasma drug levels. Consequently, it may not reach a therapeutic response or, alternatively, it may cause drug-induced toxicity.…”