Substance P/Neurokinin 1 and Trigeminal System: A Possible Link to the Pathogenesis in Sudden Perinatal Deaths

Sudden demise of a healthy fetus or a neonate is a very tragic episode in the life of parents. These deaths have been a mystery since ages but still remain unexplained. This review proposes the involvement of trigeminal nerve, neurotransmitter substance P (SP), and its receptor neurokinin 1 (NK-1R) in regulation of cardiorespiratory control in fetuses and newborns. Anomalies and immaturity of neuroregulatory systems such as trigeminal system in medulla oblongata of brainstem may provide a possible mechanism of sudden perinatal deaths. Vulnerable infants are born with respiratory center immaturity which in combination with any stressor such as cold, hypoxia, and smoking may lead to cessation of breathing and ventilatory response. SP/NK-1R may be involved in regulating the ventilatory control in neonates while it is decreased in fetal and adult life in humans, and any alterations from these may lead to irreversible sleep apnea and fatal breathing, ultimately sudden death. This review summarizes the studies performed to highlight the expression of SP or NK-1R in sudden perinatal deaths and proposes the involvement of trigeminal ganglion along with its nerve and SP/NK-1R expression alteration as one of the possible pathophysiological underlying mechanism. However, further studies are required to explore the role of SP, NK-1R, and trigeminal system in the pathogenesis of sudden infant deaths, sudden intrauterine deaths, stillbirths, and sudden deaths later in human life.