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The Light study in the Journal of Pain

gracenote

All shall be well . . .
Messages
1,537
Location
Santa Rosa, CA
Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects

Alan R. Light, Andrea T. White, Ronald W. Hughen, Kathleen C. Light

Received 30 March 2009; received in revised form 10 May 2009; accepted 1 June 2009. published online 03 August 2009.

Abstract
Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become markedly worse after exercise. Previous studies implicated dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in CFS and FMS.

We recently demonstrated that acid sensing ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These molecular receptors are found on human leukocytes along with SNS and IS genes.

Real-time, quantitative PCR showed that 19 CFS patients had lower expression of β-2 adrenergic receptors but otherwise did not differ from 16 control subjects before exercise.

After a sustained moderate exercise test, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors α-2A, β-1, β-2, and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05).

These increases were also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of physical fatigue, mental fatigue, and pain. These new findings suggest dysregulation of metabolite detecting receptors as well as SNS and IS in CFS and CFS-FMS.

Perspective
Muscle fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and CFS-FMS patients show enhanced gene expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these symptoms. These findings suggest possible new causes, points for intervention, and objective biomarkers for these disorders.


The full article is available in the Phoenix Rising Library (for Senior members who have access) or by going to the Dr. Lucinda Bateman thread here.
 

CBS

Senior Member
Messages
1,522
Light's slides in living color!

Here are the two slides on Dr. Light's work from Dr. Bateman's Webinar sponsored by the CFIDS Assoc (click to enlarge):

Light 2.jpg

Light 1.jpg

A link to Dr. Bateman's pdf's as posted on the CFIDS Assoc site: http://www.cfids.org/webinar/xmrv-slides-jan2010.pdf The two slides above are #26 and #27 in Dr. Bateman's pdf.

A link to an article on the Lights (husband and wife team) on the CFIDS Assoc site: http://www.cfids.org/cfidslink/2009/080503.asp
(Hint: If you click on the picture of the cover of the Journal Pain, you'll be taken to the online version of the abstract)

And a picture of the Light graphs on the October 2009 cover of the Journal Pain.

JPain10_2009.jpg
 

Dolphin

Senior Member
Messages
17,567
The study is great.
And those slides in particular.
And it's great to see it on the cover of the Journal of Pain.

But unfortunately, I'm not sure that the Lights have made it sufficiently clear that what they are saying about the study is just a theory. They think there is nothing wrong in the muscles (they quote one study in the paper) and hence think the body is misinterpreting signals. A much simpler explanation is that there is something going wrong in the muscle for whatever reason (there are studies which suggest there is something going wrong in the muscle).
 

CBS

Senior Member
Messages
1,522
There are actually two Dr. Lights. They are husband (Alan )and wife (Kathleen). He does animal model research and she does research on human subjects.

Here is a link to a talk she gave to OFFER in 2008: http://www.offerutah.org/kathleenlight.htm

As for the actual mechanism, I'm going to take longer look at the article this weekend (way to go Tom, you just had to bring up the whole parsimony thing! ).:D
 

gracenote

All shall be well . . .
Messages
1,537
Location
Santa Rosa, CA
adding to my vocabulary

As for the actual mechanism, I'm going to take longer look at the article this weekend (way to go Tom, you just had to bring up the whole parsimony thing! ).:D

I learn something new everyday.

parsimony |ˈprsəˌmōnē|

principle (or law) of parsimony: the scientific principle that things are usually connected or behave in the simplest or most economical way, esp. with reference to alternative evolutionary pathways.

Actually, on these forums, I learn a whole lot of new somethings every hour. :eek:
 

Dolphin

Senior Member
Messages
17,567
Thanks gracenote. I have to admit I wasn't sure what CBS was saying.

When I read the paper they did not go on so much about this theory of theirs as they have in other places where they made it sound very definite. On other occasions, they also said things like people can exercise which I am not convinced of. They seem to be coming from the fibromyalgia perspective where it is often said that there is nothing wrong in the muscles but people feel like there is.
 
A

anne

Guest
Are these the people Cort has referred to elsewhere as doing research on POTS?
 

gracenote

All shall be well . . .
Messages
1,537
Location
Santa Rosa, CA
And Now For Something Completely Different

Are these the people Cort has referred to elsewhere as doing research on POTS?

anne, is this maybe what you're thinking of?

Here is the link to Phoenix Rising and Cort's report on the Lights at the IACFS/ME Conference in Reno, Nevada, March 12-16, 2009.

And Now For Something Completely Different

This is how Cort's very interesting report begins . . .

I was fighting off sleep at this point. Wed just heard about yet another cortisol study a subject that is increasingly wearing me out. Every conference, though, has its surprises. Dr. Bateman said the Utah Group was doing some great stuff but my mouth gaped when I heard this presentation.

Dr. Allan Light has spent his career researching pain. Now that hes moving into the fatigue field his assessment is that its about 30 years behind the pain field in understanding how the problem occurs. He believes both fatigue and pain - two symptoms produced by the brain to signal problems in the body - are created by the same type of system - an interesting theory given how many FM patients experience fatigue and how many ME/CFS patients experience pain.

Dr. Light has done a good deal of background work to get where he could assess what might be causing the fatigue in ME/CFS. First he used laboratory animals to uncover two sets of sensory neurons that appear to relay fatigue and pain signals from the muscles to the brain. He then identified which receptors perceive signs of muscle injury. Once these receptors come across a substance which suggests muscle injury they presumably trigger those neurons to send a signal to the brain. The brain then sends out pain and fatigue messages in an effort to stop us from using those muscles.

Dr. Light first highlighted what kind of fatigue is present in ME/CFS. Dr. Behan and Chaudhuri about eight years ago asserted that ME/CFS patients exhibit central fatigue rather than muscular fatigue; i.e. their fatigue is not due to problems in the muscles but to problems in the central nervous system. Dr. Light also asserted that muscular fatigue - which refers to the ability to contract muscles to produce energy is not the problem in this disease.

But instead of the central nervous system, Dr. Light believes the problem occurs in the body - specifically in the sensors that monitor muscle health. These sensors which are found on white blood cells in the blood - continually monitor the blood for signs of muscle damage i.e. for increased levels of lactate, for low pH (acid)and for purines that are produced during ATP production. They include the:

ASICS - Acid sensing ion channel - associated with muscle and joint inflammation

Purinergic X Receptors (P2X4/P2X5) - sensing ATP levels - interestingly the ratio between the two may determine whether one has ME/CFS or fibromyalgia; P2X5 appears to trigger fatigue signals while P2X4 triggers pain signals.

Vannilloid = sensing heat, acid​

Dr. Light also examined receptors from the sympathetic nervous system - which regulates blood flows in response to metabolites out of the muscles, and the immune system. . .
. . . Starting with laboratory animals and moving up to healthy humans and now to fibromyalgia and chronic fatigue syndrome patients, Dr. Light is building a strong foundation for a new model for this disease. This body of work, though, is new not just to the chronic fatigue syndrome research field but to the research field as a whole. Acceptance of his ideas, if they are proved to be correct, will undoubtedly take time. . . .

"So far as I know we are the only one to have done anything in this direction in human beings at all let alone chronic fatigue syndrome and fibromyalgia patients." Dr. Kathleen Light
 

Dolphin

Senior Member
Messages
17,567
There are people researching POTS more directly e.g. one of the CAA-funded researchers:

Dr. Marvin Medow and his team at New York Medical College study postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance associated with signs and symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive deficits. Many young people with CFS also have POTS, and at least half of adults with CFS have POTS. Medow studies whether these POTS symptoms are due to reduced brain blood flow. He and his team published a paper in The American Journal of Physiology Heart and Circulatory Physiology in August 2009 describing decreased brain blood flow and altered regulation of blood flow by the brain in POTS patients. Medow and his team continue to study why blood flow is altered in CFS and are examining chemicals in the body that cause oxidative stress and molecules that affect the function of blood vessels. Subjects that participate in the Medow study also participate in the Shungu study described above. This will allow the Medow findings on blood flow mechanisms in the body to be related to the blood flow and metabolic alterations that Shungu is finding in the brain of CFS patients. This type of integrated study of blood flow alterations has the potential to improve CFS treatment.
 

Dolphin

Senior Member
Messages
17,567
The study is great.
And those slides in particular.
And it's great to see it on the cover of the Journal of Pain.

But unfortunately, I'm not sure that the Lights have made it sufficiently clear that what they are saying about the study is just a theory. They think there is nothing wrong in the muscles (they quote one study in the paper) and hence think the body is misinterpreting signals. A much simpler explanation is that there is something going wrong in the muscle for whatever reason (there are studies which suggest there is something going wrong in the muscle).

Here's one recently published article that it's not that the sensors are picking up signals that aren't there:

Abnormalities in pH Handling by Peripheral Muscle and Potential Regulation by the Autonomic Nervous System in Chronic Fatigue Syndrome

David EJ Jones MD PhD 1 , Kieren G Hollingsworth MD PhD 2 , Roy Taylor MD 2 , Andrew M Blamire PhD 2 , Julia L Newton MD PhD 1,3

Institute of Cellular Medicine1 , Newcastle Magnetic Resonance Centre2
3 Institute for Ageing and Health, Newcastle University, UK
d.e.j.jones@ncl.ac.uk

Correspondence: Professor Julia L Newton
Institute for Ageing and Health
Medical School
Framlington Place
Newcastle-upon-Tyne
NE2 4HH
UK
Tel: 0191 2824128
Email: julia.newton@nuth.nhs.uk
Copyright 2009 Blackwell Publishing Ltd

KEYWORDS
Chronic fatigue syndrome muscle bioenergetics autonomic dysfunction magnetic resonance spectroscopy

ABSTRACT
Objectives: To examine muscle acid handling following exercise in Chronic Fatigue Syndrome (CFS/ME) and the relationship with autonomic dysfunction.

Design: Observational study

Setting: Regional Fatigue Service.

Subjects & Interventions: CFS/ME (n=16) and age and sex matched normal controls (n=8) underwent phosphorus magnetic resonance spectroscopy (MRS) to evaluate pH handling during exercise. Subjects performed plantar flexion at fixed 35% load Maximum Voluntary Contraction. Heart rate variability was performed during 10 minutes supine rest using digital photophlethysmography as a measure of autonomic function.

Results: Compared to normal controls, the CFS/ME group had significant suppression of proton efflux both immediately post-exercise (CFS: 1.1 0.5 mM/min v Normal: 3.6 1.5 mM/min, p<0.001) and maximally (CFS: 2.7 3.4 mM/min v Control: 3.8 1.6 mM/min, p<0.05). Furthermore, the time taken to reach maximum proton efflux was significantly prolonged in patients (CFS: 25.6 36.1s v Normal: 3.8 5.2 s, p<0.05). In controls the rate of maximum proton efflux showed a strong inverse correlation with nadir muscle pH following exercise (r2=0.6; p<0.01). In CFS patients, in contrast, this significant normal relationship was lost (r2=0.003; p=ns). In normal individuals the maximum proton efflux following exercise were closely correlated with total heart rate variability (r2=0.7;p=0.007) this relationship was lost in CFS/ME patients (r2<0.001;p=ns).

Conclusion: Patients with CFS/ME have abnormalities in recovery of intramuscular pH following standardised exercise degree of which is related to autonomic dysfunction. This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.