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. 2021 Nov 18:8:727593.
doi: 10.3389/fmed.2021.727593. eCollection 2021.

Substance P/ Neurokinin-1 Receptor, Trigeminal Ganglion, Latency, and Coronavirus Infection-Is There Any Link?

Riffat Mehboob  1   2 , Maher Kurdi  3 , Ahmed Bamaga  4 , Njoud Aldardeir  5 , Hisham Nasief  6 , Leena H Moshref  7 , Taghreed Alsinani  8 , Almotasimbellah O Rayes  9 , Reem H Jabbad  10
Affiliations

Substance P/ Neurokinin-1 Receptor, Trigeminal Ganglion, Latency, and Coronavirus Infection-Is There Any Link?

Riffat Mehboob et al. Front Med (Lausanne). .

Abstract

Novel Severe Acute Respiratory Syndrome-Corona Virus-2 infection (SARS-CoV-2) is an acute respiratory and infectious disease. This perspective aims to provide a basic understanding of the inflammation caused by SARS-CoV-2 and its relation to the trigeminal ganglion (TG). The virus enters through the mucous membranes of the orofacial region and reaches the TG, where it resides and takes control of its peptides including Substance P (SP). SP is the main neuropeptide, neuromodulator, and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and, consequently, affects the immune cells and blood vessels to release the mediators for inflammation. Hence, cytokine storm is initiated and causes respiratory distress, bronchoconstriction, and death in complicated cases. Neurokinin-1 Receptor (NK-1R) is the receptor for SP and its antagonists, along with glucocorticoids, may be used to alleviate the symptoms and treat this infection by blocking this nociceptive pathway. SP seems to be the main culprit involved in the triggering of inflammatory pathways in SARS-CoV-2 infection. It may have a direct association with cardio-respiratory rhythm, sleep-wake cycle, nociception, and ventilatory responses and regulates many important physiological and pathological functions. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation. Here, it is further proposed that there is a possibility of latency in SARS-CoV-2 virus infection if it is acting through TG, which is the main site for other viruses that become latent.

Keywords: Substance P/ Neurokinin-1 Receptor; coronavirus; infectious disease; respiratory illness; trigeminal ganglion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
SARS-CoV-2 transmission from one human to another and Trigeminal innervation in ophthalmic, maxillary, and mandibular region.
Figure 2
Figure 2
SARS-CoV-2 entry through orofacial structures.
Figure 3
Figure 3
Schematic section of the main histological sections from the brainstem showing Trigeminal nerve and solitary nucleus, which are the main source of Substance P secretion and stimulation (28).
Figure 4
Figure 4
SARS-CoV-2 virus in trigeminal ganglion.
See this image and copyright information in PMC

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