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

Riffat Mehboob,Taghreed Alsinani,Njoud Aldardeir,Leena H Moshref,Maher Kurdi,Almotasimbellah O Rayes,Reem H Jabbad,Ahmed Bamaga,Hisham Nasief

doi:10.3389/fmed.2021.727593

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.

Highlights

Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) is responsible for causing Corona virus infection (COVID-19) which was first reported in Wuhan, China in December 2019Coronavirus and Trigeminal Ganglion but went on to affect the whole world [1]
The virus may remain in a latent form in trigeminal ganglion (TG) and may reactivate at any time, either causing infection leaving the patient asymptomatic in this condition
Herpes simplex virus type 1 (HSV-1) infects the ocular mucosal membrane and orofacial region and continues to infect the sensory neurons leading to a latent infection in TG (Figure 4)

Summary

Introduction

Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) is responsible for causing Corona virus infection (COVID-19) which was first reported in Wuhan, China in December 2019Coronavirus and Trigeminal Ganglion but went on to affect the whole world [1]. Any alteration in its secretion in response to viral infection may result in symptoms in the orofacial region [6] (Figure 1). It aggravates the condition due to its over secretion by TG neurons which affects the immune cells as well as other cells in the respiratory tract to release the mediators for cytokine storming which may be responsible for further complications.

Results

Conclusion