Intrathecal orexin failed to induce any changes in double orexin receptor-1 and -2 knockout mice.

Sleep/wake states remained unchanged both quantitatively as well as qualitatively. Cataplexy and sleep-onset REM sleep were significantly decreased in orexin knockout mice during and long after slow infusion of orexin (1 nmol/1 μL/h). Intrathecally delivered orexin was detected in the brain by radioimmunoassay at levels comparable to endogenous orexin levels. The computed tomographic scan confirmed that intrathecally administered contrast agent rapidly moved from the spinal cord to the brain. Orexin was delivered via a chronically implanted intrathecal catheter at the upper lumbar level. Here we demonstrate that the narcoleptic symptoms of orexin knockout mice can be reversed by lumbar-level intrathecal orexin delivery. Chronic intrathecal drug infusion through an implantable pump is a clinically available strategy to treat a number of neurological diseases. Although peripherally administered orexin does not efficiently penetrate the blood–brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Below are examples of how cataplexy has been successfully accommodated in the workplace. Cataplexy is the sudden loss of muscle tone or temporary paralysis caused by extreme emotion (laughter, stress, or anger). Narcolepsy–cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Cataplexy by itself is a rare disease, but is considered one of the major indications of narcolepsy.

Cataplexy examples