Trigeminal neuralgia (TN) is a unique and extremely distressing neuropathic facial pain condition. No study has directly investigated the presence of axonal loss or abnormal function involving specific sets of primary trigeminal afferents in patients with TN. These data may be relevant for identifying possible hallmark signs of concomitant continuous pain or purely paroxysmal pain and for disclosing pathophysiological mechanisms underlying pain in idiopathic TN, and this is crucial for developing effective treatment strategies. In the present project, we aim to identify specific functional and morphological abnormalities of primary trigeminal afferents in patients with TN. To do so, we will carry out a complete psychophysical, neurophysiological, and morphometric testing, combined to a genomic screen of neuronal electrogenisome in 50 patients with classical and idiopathic TN, with and without concomitant continuous pain. We will focus on sensory profiles, neurophysiological parameters, intraepidermal linear fiber density, and rare variants of genes encoding voltage gated ion channels and TRP channels. Results of the present research will be the fundamentals of the future advances being made in the management of this condition.
Benefits
The results obtained at the end of the research project will have a crucial impact at scientific, social and economic level. TN is an extremely distressing condition; a poor quality of life and suicide in severe cases have been attributed to the disorder. The uncertainty about the pathophysiological mechanisms underlying concomitant continuous pain, has been leading to an unsatisfactory therapeutic management.
Scientific impact: We will provide a complete and definitive picture of the involvement of different set of trigeminal afferent fibres in TN. These findings will clarify the mechanisms underlying the varied quality of pain and the pathophysiological mechanisms of idiopathic TN. The genotyping may contribute to defining the role of pathological variants of voltage-gated sodium channels and open the way to in vitro-functional analysis.
Social impact: We aim to gain a better understanding of TN and the currently available treatment, as well as details of any advances being made in the management of this distressing condition. We will be able to assess outcomes using the recently developed core outcome measures.
Economic impact: A better understanding of mechanisms underlying pain in TN and the identification of specific biomarkers will lead to a reduction of the economic burden for the National Health System, as a direct consequence of the reduction of the unnecessary diagnostic tests. A future benefit, in terms of burden lightening, will be due to the improved efficacy of therapies, better addressed and tailored to the patient. This will result in the definition of a common, standardized approach in the assessment and management of TN.