The role of mitochondrial dysfunctions due to oxidative and nitrosative stress...

[Firestormm]

The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?

Meeus M, Nijs J, Hermans L, Goubert D, Calders P.
Source

University of Antwerp, Faculty of Medicine and Health Sciences, Department of Rehabilitation Sciences and Physiotherapy, Pain in Motion Research Group , Antwerp , Belgium.
Abstract

Introduction:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are characterized by persistent pain and fatigue.

It is hypothesized that reactive oxygen species (ROS), caused by oxidative and nitrosative stress, by inhibiting mitochondrial function can be involved in muscle pain and central sensitization as typically seen in these patients.

Areas covered:

The current evidence regarding oxidative and nitrosative stress and mitochondrial dysfunction in CFS and FM is presented in relation to chronic widespread pain.

Mitochondrial dysfunction has been shown in leukocytes of CFS patients and in muscle cells of FM patients, which could explain the muscle pain.

Additionally, if mitochondrial dysfunction is also present in central neural cells, this could result in lowered ATP pools in neural cells, leading to generalized hypersensitivity and chronic widespread pain.

Expert opinion:

Increased ROS in CFS and FM, resulting in impaired mitochondrial function and reduced ATP in muscle and neural cells, might lead to chronic widespread pain in these patients.

Therefore, targeting increased ROS by antioxidants and targeting the mitochondrial biogenesis could offer a solution for the chronic pain in these patients.

The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area.

 

[MeSci]

"The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area."

Really?

 

[Firestormm]

"The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area."

Really?

I did wonder who would highlight this aspect of it first

Way I see it is that nobody has actually looked at this for ME have they? At least I suppose these authors are leaving it open. They aren't saying - 'GET will restore any dysfunction'. And if for example exercise is not restoring any presumed dysfunction it is important to understand why this might be... or something.

Here's what ME/CFS Evolving Science (Facebook) had to say - out of interest and unconnected to your comment/concern/issue:

ROS/iNOS signalling and mitochondrial functioning are the subject of intensive research lately.

Mainly outside the CFS-specific domain, for now, but I hope we may see collaborations in the future.

Did you know, that there's a very knowledgeable group in Switzerland on this subject? In Zürich, since Jan 2013: Prof Michael Ristow- Energy metabolism Lab: http://www.energymetab.ethz.ch/ Ristow focuses on the relationship with longevity, but his elaboration of 'mitochondrial hormesis' ideas is impressive. (lv)

and

ROS signaling has to do with many metabolic feedback loops. It's not just a question of neutralizing excess ROS with antioxidants. I hope the research on these issues advances fast. (lv)

I don't know who 'Evolving Science' are or who is answering the questions here. I think they originate in Belgium? Not sure. Might be a collaboration with other patients from across the pond. Anyway, I often 'tap' into them for new research articles. Good source

 

[lansbergen]

I did wonder who would highlight this aspect of it first

Way I see it is that nobody has actually looked at this for ME have they? At least I suppose these authors are leaving it open. They aren't saying - 'GET will restore any dysfunction'. And if for example exercise is not restoring any presumed dysfunction it is important to understand why this might be... or something.

I know what happened in the past.

 

[Firestormm]

I know what happened in the past.

Have you read or hear of any papers linking mitochondria to ME and exercise as a therapy for restoration? Thanks Ian

 

[lansbergen]

Have you read or hear of any papers linking mitochondria to ME and exercise as a therapy for restoration? Thanks Ian

No

 

[MeSci]

Here's what ME/CFS Evolving Science (Facebook) had to say - out of interest and unconnected to your comment/concern/issue:
...

"ROS signaling has to do with many metabolic feedback loops. It's not just a question of neutralizing excess ROS with antioxidants. I hope the research on these issues advances fast"

I agree with that. I can't help wondering whether 'antioxidants' are just an erroneous modern obsession, like the 'salt and fat are bad' one.

I know that biochemistry is complex, but there seems to be evidence that we have a problem with oxygen utilisation, and this could be due to acidosis (although whenever I try a search on this I get hits that discuss the reverse causation). Acidic fluids are characterised by H+ ions, so it would perhaps make more sense to be neutralising these, which is what I am attempting to do.

I have not studied the biochemistry of reactive oxygen species but I would be concerned about anything that reduced overall oxygen in cells and tissues.

As a vegan who consumes a lot of fresh veg, etc., and takes multivitamin supplements and other supplements whose properties include antioxidant ones, I feel that it is unlikely that I am deficient in antioxidants.

 

[Gijs]

I think the PH value (high and low) and reduced supply of oxygen can be a primary problem in this disease. When thePH levels are not normal you get infections and reactivation. PH is everywhere in the body and plays a major rol controlling the internal environment. Maybe a metabolic problem of handling PH is the course of ME.

 

[peggy-sue]

It has been found that cultured muscle cells produce lactic acid at 20 times the "normal" rate in PWME in reponse to "exercise".
We can't seem to get into utilising aerobic metabolism, but are stuck in anaerobic mode the whole time.

As the cells were cultured, it has to be something which can be passed on genetically. A retrovirus in the mitochondria would be passed on in this way.

Does this fit in?

(but stuff doing exercise to enhance mito. function! MY evidence, gathered personally on a daily basis for over 10 years, proves exercise makes me ill and puts me into vile payback.)

 

[MeSci]

I think the PH value (high and low) and reduced supply of oxygen can be a primary problem in this disease. When thePH levels are not normal you get infections and reactivation. PH is everywhere in the body and plays a major rol controlling the internal environment. Maybe a metabolic problem of handling PH is the course of ME.

It can be hard to untangle cause and effect, but abnormal carbohydrate metabolism can be a source of low pH, and the leaky gut diet corrects this.

But the muscle and nerve sources of acidosis are less clear, to me at least. Overexertion causes acidosis, but is this due to inability to use oxygen normally, hence the production and use of lactate instead, or is the lactate production the cause of the oxygen-utilisation problem, or is it both - a vicious cycle?

 

[MeSci]

It has been found that cultured muscle cells produce lactic acid at 20 times the "normal" rate in PWME in reponse to "exercise".
We can't seem to get into utilising aerobic metabolism, but are stuck in anaerobic mode the whole time.

As the cells were cultured, it has to be something which can be passed on genetically. A retrovirus in the mitochondria would be passed on in this way.

Does this fit in?

I don't think it has to be inherited, although there may be a genetic predisposition in at least some cases. Almost all illnesses are due to a combination of inherited factors and acquired ones.

But there is now known to be more than one kind of inherited genetic abnormality - those in the genome and those in the epigenome. There is little or nothing we can do about the former, other than gene therapy (which is not very succesful). But there seems to be a lot we can do about the epigenome through lifestyle changes, such as diet.

The in vitro finding is very interesting, as it shows that there is something wrong with the cells themselves, not just the environment in which they are operating.

 

[biophile]

Therefore, targeting increased ROS by antioxidants and targeting the mitochondrial biogenesis could offer a solution for the chronic pain in these patients.The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area.

Way I see it is that nobody has actually looked at this for ME have they? At least I suppose these authors are leaving it open. They aren't saying - 'GET will restore any dysfunction'. And if for example exercise is not restoring any presumed dysfunction it is important to understand why this might be... or something.

CBT/GET proponents tend to believe that any mitochondrial changes are due to deconditioning and are reversible with exercise. AFAIK the authors of this paper are proponents of rehabilitative approaches, including CBT/GET, so yes, it is possible they believe that GET could restore any dysfunction. I am fairly certain at least some of them including Nijs have signed off on papers which state that the significant benefits of CBT/GET are undeniable or words to that effect. I guess we would need to read the full text to better understand what they mean in this recent paper.

It is certainly understandable why patients are generally concerned that the exercise fad manages a mention in just about every published paper on ME/CFS no matter the main subject of the paper, which itself is also understandable because researchers tend to put their work in conservative context with popular attitudes found in their own field. If evil spirits or the flying spaghetti monster were seriously believed to play a role, you can be sure that many researchers, especially those sympathetic to them, would be at least be making an uncritical passing comment about it in their papers.

There are already Phase 1 and Phase 2 trials looking into combining mitochondrial nutraceuticals and graded exercise:

http://clinicaltrials.gov/ct2/show/NCT01872351
http://clinicaltrials.gov/ct2/show/NCT01471652

 

[MeSci]

If evil spirits or the flying spaghetti monster were seriously believed to play a role, you can be sure that many researchers, especially those sympathetic to them, would be at least be making an uncritical passing comment about it in their papers.

Have evil spirits and the flying spaghetti monster been disproved as causes? Should I cross them off my list of credible theories?