Fatigue during illness, Orexin as possible new treatment target

Waverunner

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During chronic or acute illness the body draws away ressources from non-vital systems. So for example digestion gets reduced and you lose appetite. Moreover people mostly suffer from loss of motivation and loss of physical activity. Scientists found out that there consists a sort of neurons which are highly prone to inflammation and control sleep, motivation, appetite and movement. Disruption of the so called orexin system seems to cause all the reactions. When the orexin system was restored in ill mice not only appetite but motivation, movement and healthy sleep were restored. Since in my eyes the body of PWCs seems highly desychronized, as if the immune system was stuck in fighting an infection, this maybe helpful. It will likely not treat the cause if there is a direct one like a virus but it would help our bodies to sleep normal again, it will improve digestion and give back motivation and energy.

http://www.sciencedaily.com/releases/2011/08/110803092314.htm

Scientists Identify What Makes Us Feel 'Bad' When We're Sick, How to Treat It
ScienceDaily (Aug. 2, 2011) A signaling system in the brain previously shown to regulate sleep is also responsible for inducing lethargy during illness, according to research conducted at Oregon Health & Science University Doernbecher Children's Hospital.

This research is particularly meaningful because it implies that a new class of drugs developed to treat sleep disorders can reverse the inactivity and exhaustion brought on by acute illness. Although the sleep drugs were initially designed to treat narcolepsy, they have the potential to restore energy and motivation in patients with acute and chronic disease, the researchers report. Their findings are published in the The Journal of Neuroscience.
"We all know what it means to feel 'bad' when we're acutely ill. In particular, patients with chronic diseases experience a compromise in motivated behaviors. They don't feel like getting up and doing anything. Yet the brain mechanisms behind this common experience have remained obscure," said Daniel L. Marks, M.D., Ph.D., principal investigator and associate professor of pediatrics in the Pap Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.
"Our lab has found that the neurotransmitter system thought to be primarily involved in the induction of sleep is actually extremely important in maintaining motivation and movement during acute and chronic illness," Marks explained.
Research has shown that in response to illness, animals divert all their energy to fight infection. Lethargy, fever and loss of appetite are symptoms of the body's highly organized strategy to sacrifice biological and physiological priorities to provide the greatest chance of survival.
Although previous studies have identified the neurotransmitter system in the brain responsible for inducing fever and loss of appetite in response to disease, the mechanism for suppressing physical activity and motivation, and the means to treat it, has been unclear -- until now.
To determine the cause of illness-induced lethargy, Marks and colleagues studied the brains of rats, the neuroactivity of which closely mimics human brains. They determined that acute and chronic inflammation-induced lethargy is brought about by a specific population of inflammation-sensitive neurons located near the neurotransmitter system that controls physical activity and arousal, known as the orexin system. When the researchers injected the rats with orexin, they were able to restore orexin signaling and, thus, restore motivated behaviors and movement.
This research demonstrates that orexin replacement is a viable therapeutic avenue for sickness-induced lethargy, the researchers explain. Because chronic disruption of this crucial neurotransmitter system leads to profound sleep disturbance and loss of motivated behaviors, they propose that drugs that mimic orexin would be useful in chronically ill patients to improve quality of life and independent living.
"There is a very exciting opportunity to quickly translate these findings into clinical practice," Marks said. "Because the role of orexin in sleep disorders like narcolepsy has been known for several years, the drug development efforts aimed at restoring orexin signaling are at an advanced state and nearly ready for clinical application."
The study, "Inflammation-induced lethargy is mediated by suppression of orexin neuron activity," was funded by the National Institutes of Health.
Other members of the research team include: Aaron Grossberg, XinXia Zhu, Pete Levasseur, and Theodore Braun, all of Oregon Health & Science University; and Gina Marie Leinninger and Martin Myers, of the University of Michigan.
 

ukxmrv

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If the fatigue that ME and CFS patients is a protective behaviour to save us from further damage (a la Cheney) or due to heart flow problems etc (more Cheney and the lastest from Newton) then injecting us with a drug to restore "motivated behaviour" will possibly be to our detriment.

I don't have appetite problems or what I think of as motivated behaviour so wonder if they are talking about something else anyway?
 

Esther12

Senior Member
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13,774
I kind of agree with ukXMRV - surely for lots of these people there's a reason why this response has evolved.

Maybe for some it's triggered in error, but over-riding this defence mechanism without knowing why it's operating sounds like it would bring some unknown risks. Still, it's an interesting bit of research - lets hope it leads on to something useful for us. Thanks for posting it.
 

Snow Leopard

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This research is a little overstated in terms of our understanding (as the media always likes to do), but it is interesting and I want to see RCTs soon!
 

Waverunner

Senior Member
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1,079
Medicine as always is very difficult. If our bodies protect us from something it may be wise not to disrupt it. On the other side we have to take into account that if our body fights something over years and at the same time impairs digestion, sleep, motivation, movement etc. this will cause a cascade of other symptoms and problems. Our bodies work at their limits but they don't get rid of any infection or whatever causes CFS.
 
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