During the course of evolution invertebrates and vertebrates have maintained common signaling molecules, such as neuropeptides. For example, complete hormonal-enzymatic systems for the biosynthesis of opioid peptides have been found in both the CNS and immune systems of these animals. These signaling molecules have been found in the blood circulation and act as immunomodulators. In vertebrates, release of the signaling molecules occurs during stress (cognitive or pathogens), which triggers the hypothalamo-hypophysial-adrenal axis. Similarly, these neuropeptides are used as messengers to initiate and stimulate the innate immune response in invertebrates. Thus, the crosstalk between nervous and immune systems has an ancient evolutionary origin and the messengers used have been conserved during the course of evolution reflecting their vital importance.