Coordinating Panel on Rare Neurological Diseases Sleep disorders

Better understanding of RLS and narcolepsy neurobiology

Anectdotal evidence has pointed out clinical improvements narcolepsy-specific symptoms following treatment of painful conditions with opiates. Post-mortem findings in human brains revealed a significant increase of hypocretin neurons on patients

Anectdotal evidence has pointed out clinical improvements narcolepsy-specific symptoms following treatment of painful conditions with opiates. Post-mortem findings in human brains revealed a significant increase of hypocretin neurons on patients abusing opiates. Thannickal et al. showed that 14-day administration of morphine led to a significant increase of hypocretin neurons in narcoleptic mice and, moreover, to a marked decrease of cataplexy. These findings suggest a potential role of opiate agonists in the treatment of this rare and debilitating condition.

Restless legs syndrome (RLS), a common sensorimotor disorder, frequently leads to non-restorative sleep with its daytime sequelae impacting the quality of life of patients. Ferré et al. attempt to integrate experimental and clinical findings in a heuristic pathogenetic model. Brain iron deficiency leads to hyperglutamatergic and hyperdominergic states which determine the dysfunction of cortico-striato-thalamic-cortical circuits. Recent evidence also points to a hypoadenosinergic state and, thus, providing the pathophysiological link between sensorimotor signs and hyperarousal.

 

references:

Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy.
Thannickal TC, John J, Shan L, Swaab DF, Wu MF, Ramanathan L, McGregor R, Chew KT, Cornford M, Yamanaka A, Inutsuka A, Fronczek R, Lammers GJ, Worley PF, Siegel JM. Sci Transl Med. 2018 Jun 27;10(447). pii: eaao4953. doi: 10.1126/scitranslmed.aao4953.

New Insights into the Neurobiology of Restless Legs Syndrome. Ferré S, García-Borreguero D, Allen RP, Earley CJ. Neuroscientist. 2019 Apr;25(2):113-125. doi: 10.1177/1073858418791763. Epub 2018 Jul 26.