The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA),[1] contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system;[2] this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others.

[2][8] The histaminergic, dopaminergic, serotonergic, noradrenergic, and cholinergic nuclei which the lateral hypothalamic orexin neurons project onto constitute the primary components of the ascending reticular activating system.

Two of the most commonly noted functions of orexin peptides in the lateral hypothalamus are the promotion of feeding behavior and arousal (i.e., wakefulness).

[6][15][16] Narcolepsy is associated with a marked reduction in the number of orexinergic projection neurons from the lateral hypothalamus and very low orexin peptides in cerebrospinal fluid.

[17] Evidence suggest that OX1 neurons that synapse onto the dorsal nucleus of the vagus nerve and parts of the brain stem may play a role in the pathophysiology of chronic pain and visceral hypersensitivity in functional gastrointestinal disorders.