Moreover, an excitatory Tac1 spinal-brainstem circuit mediates noxious responses in rodents (Barik et al., 2018; Gutierrez et al., 2019) and deletion of the Tac1 gene in mice increases the inhibitory effects of opioid drugs, suggesting that substance P could reverse respiratory depression by opioid drugs (Takita et al., 2000; Berner et al., 2012). Here, TAC1 is linked to Respiratory insufficiency due to muscle weakness.