Neurotensin is an endogenous tridecapeptide that exhibits antinociceptive, pro-inflammatory, and gastrointestinal motility modulating activities; it binds and activates neurotensin (NTS) receptors. Neurotensin induces contractions in smooth muscle cells, playing a role in regulating digestive activity in vitro and in vivo. Additionally, neurotensin induces intracellular Ca2+ release, activating non-selective cation channels and altering pacemaker currents involved in gastrointestinal and colonic motility. In animal models, neurotensin displays sympatho-inhibitory activity, decreases blood pressure and heart rate. Neurotensin exerts its actions through activation of neurotensin receptors; activation of these receptors also stimulates orexin neurons, suggesting a role for neurotensin in mediation of reward, feeding, and wakefulness.