Olfactory-Trigeminal Interactions in Patients with Parkinson's Disease

Abstract

Olfactory dysfunction (OD) is a highly frequent early non-motor symptom of Parkinson's disease (PD). An important step to potentially use OD for the development of early diagnostic tools of PD is to differentiate PD-related OD from other forms of non-parkinsonian OD (NPOD: postviral, sinunasal, post-traumatic, and idiopathic OD). Measuring non-olfactory chemosensory modalities, especially the trigeminal system, may allow to characterize a PD-specific olfactory profile. We here review the literature on PD-specific chemosensory alteration patterns compared with NPOD. Specifically, we focused on the impact of PD on the trigeminal system and particularly on the interaction between olfactory and trigeminal systems. As this interaction is seemingly affected in a disease-specific manner, we propose a model of interaction between both chemosensory systems that is distinct for PD-related OD and NPOD. These patterns of chemosensory impairment still need to be confirmed in prodromal PD; nevertheless, appropriate chemosensory tests may eventually help to develop diagnostic tools to identify individuals at risks for PD.

Keywords: Parkinson’s disease; chemosensory interactions; olfactory dysfunction; trigeminal system.

Figure 1.

Proposed model of olfactory–trigeminal interactions. (a) In individuals with an intact sense of smell: olfactory and trigeminal systems are known to interact together and potentially exchange information. (1) In periphery, that is at the level of the nasal mucosa where the trigeminal nerve innervates the olfactory epithelium. (2) At the level of the olfactory bulb where collaterals of the trigeminal nerve re-enter the glomerular layer of the olfactory bulb as shown in rodents. (3) At the level of the central nervous system where both systems show overlapping brain processing areas and the olfactory input is thought to lead to a higher trigeminal response. (b) In patients with NPOD: primary alterations of the peripheral olfactory system can affect the interaction in periphery and the input of information towards the olfactory bulb and olfactory centers explaining the reduced behavioral and central trigeminal response due to the missing amplification of the trigeminal response by olfactory input. Moreover, the reduced/missing activation of the olfactory bulb’s neurons prevents their interaction with the collateral of the trigeminal nerve that may lead to a peripheral disinhibition hence the increased peripheral responsiveness. (c) In patients with PD: alterations of the olfactory bulb may lead to a disrupted transmission of information towards olfactory centers leading to a reduced olfactory response. The missing amplification of the trigeminal response by a reduced olfactory input seems to be compensated by mechanisms implicating alterations in functional connectivity and changes in modularity within the chemosensory network. Therefore, central trigeminal response is not different than in controls despite the impaired olfactory function. We believe the olfactory bulb’s neurons to receive normal olfactory input from the periphery and that mechanisms of trigeminal inhibition proposed in controls would still take place in PD patients, leading to an intact peripheral response as well. OB, olfactory bulb; OLF, olfactory; TRIG, trigeminal; INT, interaction; r, receptor.