Are Parkinson's and ME related?

[helen41]

I'm looking for links to researchers or papers that look at both diseases. If anyone has knowledge of a connection between the 2, I would appreciate some input. Thanks

 

[richvank]

I'm looking for links to researchers or papers that look at both diseases. If anyone has knowledge of a connection between the 2, I would appreciate some input. Thanks

Hi, Helen.

Dr. Amy Yasko has reported having some success in treating the methylation cycle in Parkinson's and other adult neurological diseases. This is the same approach she uses for autism, and that I have adopted for treating ME/CFS as well. You might read her book Autism, Pathways to Recovery. She also has an internet forum at www.ch3nutrigenomics.com.

You might also look into Dr. David Perlmutter's work. He is in Florida, and has been treating Parkinson's for several years using IV glutathione. Glutathione depletion is linked to the partial block in the methylation cycle.

Rich

 

[Rrrr]

i have me/cfs and my dad has parkinsons....

 

[Marg]

A friend that was doing a lot of research at Harvard sent me a paper on this subject. There are a lot of people with this illness that have Parkinson's in their families. I do, my grandfather had it and now two uncles do. I have asked people and quite a few do, not all.

 

[Ernie]

I have me/cfs and my dad has parkinson's too. I've also tested positive for HGRV's.

 

[Sing]

I believe there is a smilarity in that both diseases show a lack of dopamine in the brain. The general slow down and brain fog in ME/CFS could be seen as a result of damage to the Reticular Activating System in the brain stem, where the dopamine producing cells are. This is the part of the brain that maintains normal rhythms in the brain. My thinking on this comes from Dr. Richard Bruno's work comparing ME/CFS to Post Polio Fatigue in which there is definitely damage to this part of the brain, sometimes extending to the nearby hypothalamus at the top of the endocrine system. In Parkinsons, there is a lack of dopamine which affects the brain in a more specific way. I am forgetting exactly what happens there. Can't add more to this, but perhaps this will set some more thoughts in motion.

 

[Persimmon]

I have a family member who had Parkinson's too.

On the other hand, the the prevalence of Parkinson's is high among older people: 0.5-1% among those 65-69; 1-3% among those over 80. So, if an association exists, you'd expect to see higher Parkinson's prevalence rates than these among the relatives of ME/CFS patients.

 

[*GG*]

My Dr has Parkinsons, anything you want me to ask him when I see him at the beginning of September?

GG

 

[lilian54]

just saw this thread - I too am very interested in any info about links, I have me/cfs and my brother has Parkinson's.

PWP are often low in B12 and glutathione suggesting problems with the methylation cycle.
http://www.ncbi.nlm.nih.gov/pubmed/22367474
http://www.ncbi.nlm.nih.gov/pubmed/18400456 and http://onlinelibrary.wiley.com/doi/10.1002/ana.410360305/abstract
but it seems that taking glutathione directly doesn't help http://www.parkinson.org/NationalPa...s/56/56b9bd0e-0334-429f-aa7e-7fdcba48b6cb.pdf or if it does, the effect is temporary.
I got onto a possible link because my brother and I both have peripheral neuropathy - numbness and odd sensations in our feet. I've been taking B12/folate for years, which controls both this and many other symptoms.
I'd be interested in seeing your paper, Marg if you could link or send? Also, if anyone knows of PWP using one of the protocols - Rich's, Fredd's or Dr Yasko's - and what results.
many thanks

 

[merylg]

Found this interesting video. Research has found a genetic association in Parkinson's is also linked with monocytes suggesting a possible Immune basis to the disease.

http://www.ucl.ac.uk/ukpdc/news-publications/video-lrrk2-genetics-nick-wood

LRRK2 has been linked with Parkinson's, Crohn's & Leprosy.

 

[merylg]

Mitochondrial function appears to be involved in Parkinson's Disease:

" One of the most consistent observations related to PD is the involvement of mitochondria. Most of the genes linked to PD appear to affect mitochondrial function, and our recent study using Caenorhabditis elegans lines expressing LRRK2 show that LRRK2 modulates neuronal vulnerability to mitochondrial toxins much like mutations in parkin, PINK1, DJ-1, or α-synuclein (2, 49,–,53). It is possible that the role of LRRK2 in actin dynamics, autophagy, and cell death all connect to PD by functional convergence on mitochondria because mitochondria are trafficked by cytoskeletal elements, including actin filaments and microtubules, mitochondria turnover is mediated by autophagy, and apoptosis is also mediated by mitochondria."

http://www.jbc.org/content/286/18/16140.full

 

[alice]

Two older brothers who had Parkinson's Disease....

 

[alex3619]

I just want to add to the list. I have ME and my uncle had Parkinsons. We also have hypermobility in the family, though I am not hypermobile.

 

[GcMAF Australia]

I'm looking for links to researchers or papers that look at both diseases. If anyone has knowledge of a connection between the 2, I would appreciate some input. Thanks

This is a damn good quetsion.

• Low vitamin D

• gut bacteria are involved in both

• Also both are "inflammatory diseases"
• A lot of diseases have some other infection, bacterial or viral. (Maybe a good indicator is to have nagalase tests done)

Inflammatory diseases have high levels of "inflammatory" cytokines such as IL-1β, TNF-α and IL-, IL-1. Tests for some of these can be difficult to interpret.

Melatonin is anti-inflammatory http://www.ncbi.nlm.nih.gov/pubmed/21358973. In this review, the authors examine the effect of melatonin on several neurological diseases with inflammatory components, including dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, stroke, and brain ischemia/reperfusion but also in traumatic CNS injuries (traumatic brain and spinal cord injury)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987579/?tool=pubmed The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson's disease.
http://www.ncbi.nlm.nih.gov/pubmed/18976327 The PD group presented with significantly increased IL-10 levels when compared with the control group

http://www.ncbi.nlm.nih.gov/pubmed/21887889 Osmotic pump infusion of IL-10, a global inhibitor of cytokine synthesis, protected against LPS-induced cell death of dopaminergic neurons, with a corresponding decrease in the number of activated microglia, suggesting that the reduction in microglia-mediated release of inflammatory mediators may contribute to the anti-inflammatory effect of IL-10.
http://www.ncbi.nlm.nih.gov/pubmed/12964024 In this report we demonstrate that cyclic exercise over months results in a significant increase in the rise of plasma anti-inflammatory signal molecules, such as interleukin-10 and adrenocorticotropin.

now for CFS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849324/?tool=pubmed One major hypothesis for the cause of CFS is an immune dysregulation of unknown etiology with high levels of proinflammatory cytokines producing the CFS symptom complex. ...However, a very different and alternative hypothesis focuses on the common complaint in CFS of unrefreshing sleep (4). Recent work suggests that sleep is under the control of a cytokine/sleep network where normal sleep follows a balanced secretion of pro- and anti-inflammatory cytokines

http://www.ncbi.nlm.nih.gov/pubmed/17544255 CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed
http://www.ncbi.nlm.nih.gov/pubmed/20447453 High Th2 marker expression but weak interaction patterns pointed to an established Th2 inflammatory milieu. Similarly, altered associations in CFS provided indirect evidence of diminished NK cell responsiveness to IL-12 and LT-α stimulus. These observations are consistent with several processes active in latent viral infection and would not have been uncovered by assessing marker expression alone. Furthermore this analysis identifies key sub-networks such as IL-2:IFN-γ:TNF-α that might be targeted in restoring normal immune function.

Here is a rhetorical question--
Who said diseases are different?? I consider them to be a spectrum of the same disease.
This brings lateral thinking to the arena.
So therefore 1 treatment can treat or help several diseases.
eg
GcMAF,for cancer AIDS, viruses, CFS & http://www.gcmaf.eu/info/
"research shows GcMAF can reverse diseases that attack the immune system like chronic inflamation, bacterial and viral infections, Autism, Chronic Herpes, Chronic Acne, CFS, XMRV, Lyme disease, AIDS, HIV, Fibromyalgia (all of which we've had success with ourselves), osteoporosis, Hodgkin’s, Lupus, MS, Parkinson’s, and various types of Immune dysfunction"

metformin for diabetes and cancer
I have used a CFS treatment to treat a skin cancer.

Reveal therapies are looking at adjusting cytokines and GcMAF activation for many diseases http://www.revealtherapies.com/
(Hopefully coming to a country near to you soon, and me)
(sorry i cant think to finish this bit at the moment)

 

[currer]

My brother has parkinsons and myself and my sister have ME. My sister and I became ill (separately, we were in different towns) in our early 20s, and my brother became ill with Parkinsons at 50 - thats YOUNG for Parkinsons.

I have a vague memory that Dr mikovits mentioned Parkinsons and ME as being diseases where the immune system was activated in the same way.

http://forums.phoenixrising.me/index.php?threads/population-statistics-for-chronic-diseases.14331/
I started this thread to try to find out whether Parkinsons had become more prevalent in recent years. Our governments do not seem to keep statistics on chronic diseases.

 

[Marlène]

When I started the methylation protocol explained on this forum because of very low vit B12 (50 pmol), I started to shake like a parkinson patient for several days as soon as I raised the dose.
(I went from 1/10 to 1/6 of a tablet of methyl B12 and dibencozide B12.)

 

[GcMAF Australia]

My brother has parkinsons and myself and my sister have ME. My sister and I became ill (separately, we were in different towns) in our early 20s, and my brother became ill with Parkinsons at 50 - thats YOUNG for Parkinsons.

I have a vague memory that Dr mikovits mentioned Parkinsons and ME as being diseases where the immune system was activated in the same way.

http://forums.phoenixrising.me/index.php?threads/population-statistics-for-chronic-diseases.14331/
I started this thread to try to find out whether Parkinsons had become more prevalent in recent years. Our governments do not seem to keep statistics on chronic diseases.

http://www.change.org/petitions/min...h-for-patients-with-myalgic-encephalomyelitis

ME has increased in Canada, maybe able to get stats from their 2010 Survey mentioned in this post
Hope this helps
GcMAF

 

[Lisette]

http://www.ncbi.nlm.nih.gov/pubmed/19929732
Hi,
This article discusses cyanobacteria, and how the illnesses of Parkinson's, ALS and Alzheimer's were seemingly related in the diets of people in Guam (and another island, I believe) who ate a certain ground up bean product. This was discussed in Discover magazine, but I can't remember the issue number right now.

The compound is BMAA, which could start you out on your google search.

What I find interesting is that one substance caused three different neurological illnesses that all present extremely differently. I wonder if ME was a diagnosed illness in parts of the world where it is probably still not considered, if this study would have also shown that it can cause this illness as well.

I don't believe that any one substance can cause ME for everyone. But it's possible that certain substances can cause certain illnesses for certain genetic populations. Cyanobacteria is found in algae blooms and it is usually treated in water supplies. Yet paradoxically, cyanobacteria is being used on purpose to treat water for arsenic.

When it comes to genetic populations, here is an example of what I mean. A 2010 study was published (and can be found on the website called Toxicogenomics Data Base which is sort of like a PubMed for how toxins act upon genetic expression) about how a particular toxic substance was injected into two different rodents-- hamster and guinea pig. The hamster died from this, but the guinea pig was immune to it. To me, to think that outcomes on studies might all depend on which segment of a species is used boggles my mind in its implications.

I read about most of these things in Discover, a year or so ago. It is difficult for me to go back and find information. I always say I will post more, but then I never do. So, I hope this gets someone's more functional brain curious.

This is just one more thing to throw into the soup.

 

[Sallysblooms]

Lillian, there are supplements and diet for Peripheral Neuropathy. B12 is only one of them.

 

[Marg]

My grandfather had Parkinson's and now my uncle has it. Here is some research on it.
Prevalence, classification, and etiology of pain in Parkinson's disease: association between Parkinson's disease and fibromyalgia or chronic widespread pain.

Toda K, Harada T.
Source

Department of Rehabilitation, Hatsukaichi Memorial Hospital, Hiroshima, Japan. goutattack@yahoo.co.jp
Abstract

Parkinson's disease (PD) is characterized by resting tremor, slow and decreased movement (hypokinesia and akinesia), rigidity, postural instability, problems with gait, and coordination. The prevalence of PD is between 0.1% and 0.3% in the general population and between 1% and 2% in persons 65 years of age or older. Patients with PD are more likely to suffer from pain. Indeed, the chief complaint of patients with severe motor disturbance and severe pain is pain rather than motor disturbance. Fibromyalgia (FM) is defined by widespread pain (pain in the left and right sides of the body, pain above the waist, pain below the waist, and axial skeletal pain) for more than 3 months and the presence of at least 11 of the 18 specified tender points. FM and chronic widespread pain (CWP), which is usually an incomplete form of FM, cause pain in the musculoskeletal region, but their etiologies are unknown. Therefore, it is almost impossible to determine whether or not pain in the musculoskeletal region is in the musculoskeletal origin. We suspect that dysfunction or degeneration of the nerves that control pain, mind, and movement in the brain causes FM, depression, and PD, respectively. When pain in PD is discussed, FM and CWP should be considered because their prevalence is high. Patients with PD may be likely to suffer from FM and CWP; however, the prevalence of FM and CWP in patients with PD has not been reported. Here, we discuss the relationship between PD and FM or CWP.
PMID:
20805678
[PubMed - indexed for MEDLINE]
Free full text
Related citations
Mayo Clin Proc. 2009 Feb;84(2):134-8.
Clinical and genetic description of a family with a high prevalence of autosomal dominant restless legs syndrome.

Young JE, Vilariño-Güell C, Lin SC, Wszolek ZK, Farrer MJ.
Source

Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.
Abstract

OBJECTIVE:

To conduct clinical and molecular genetic analyses of the members of an extended family in Central Indiana with a high prevalence of restless legs syndrome (RLS).
PARTICIPANTS AND METHODS:

From February 1, 2006, through August 31, 2008, we collected data from members of this family, which is of English descent. Genealogical methods were used to expand the family tree, and family members were screened with an RLS questionnaire. Telephone interviews and personal examinations were performed at Mayo Clinic and during a field trip to Central Indiana. Blood samples were collected for molecular genetic analysis. A follow-up telephone interview was conducted 1 year later.
RESULTS:

The family tree spans 7 generations with 88 living members, 30 of whom meet the criteria for diagnosis of RLS established by the International Restless Legs Syndrome Study Group. Three affected family members also have Parkinson disease or essential tremor. The mode of RLS inheritance is compatible with an autosomal dominant pattern. The affected family members do not exhibit linkage to the 5 known RLS loci or mutations in the RLS susceptibility genes MEIS1 and BTBD9.
CONCLUSION:

Of 88 members of this single extended family in Central Indiana, 30 were diagnosed as having RLS. Because our analysis shows that the disease is not linked to any of the known RLS loci or risk-associated genes, we postulate that members of this family may carry a gene mutation in a novel genetic locus.
PMID:
19181647
[PubMed - indexed for MEDLINE]
PMCID: PMC2664577
Free PMC Article


3.
Mol Nutr Food Res. 2008 Jul;52(7):780-8.
Medication-induced mitochondrial damage and disease.

Neustadt J, Pieczenik SR.
Source

Montana Integrative Medicine, Bozeman, MT 59718, USA. drneustadt@gmail.com
Abstract

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health and disease. Damage to mitochondria is now understood to play a role in the pathogenesis of a wide range of seemingly unrelated disorders such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis. Medications have now emerged as a major cause of mitochondrial damage, which may explain many adverse effects. All classes of psychotropic drugs have been documented to damage mitochondria, as have stain medications, analgesics such as acetaminophen, and many others. While targeted nutrient therapies using antioxidants or their precursors (e. g., N-acetylcysteine) hold promise for improving mitochondrial function, there are large gaps in our knowledge. The most rational approach is to understand the mechanisms underlying mitochondrial damage for specific medications and attempt to counteract their deleterious effects with nutritional therapies. This article reviews our basic understanding of how mitochondria function and how medications damage mitochondria to create their occasionally fatal adverse effects.
PMID:
18626887
[PubMed - indexed for MEDLINE]
Related citations


4.
Exp Mol Pathol. 2007 Aug;83(1):84-92. Epub 2007 Jan 18.
Mitochondrial dysfunction and molecular pathways of disease.

Pieczenik SR, Neustadt J.
Source

drneustadt@gmail.com
Abstract

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health, disease, and aging. A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis, have underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production, the accumulation of mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction. Antioxidant therapies hold promise for improving mitochondrial performance. Physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them. If in the next 50 years advances in mitochondrial treatments match the immense increase in knowledge about mitochondrial function that has occurred in the last 50 years, mitochondrial diseases and dysfunction will largely be a medical triumph.
PMID:
17239370
[PubMed - indexed for MEDLINE]
Parkinsonism Relat Disord. 2007 Jul;13(5):312-4. Epub 2006 Jul 7.
Parkinson disease patient with fibromyalgia: a case report.

Toda K, Harada T, Ishizaki F, Horie N, Yamada T.
Source

Department of Rehabilitation, Hiroshima Prefectural Rehabilitation Center, 295-3 Taguchi, Saijyou, Higashi-Hiroshima, Hiroshima 739-0036, Japan. goutattack@yahoo.co.jp
Abstract

Parkinson's disease (PD) is characterized by motor disturbances such as tremor, slow movement and rigidity. Also, pain is a common symptom in patients with PD. The prevalence of pain is 40-75% in patients with PD. Physicians should pay attention to pain in patient with PD. We report a PD patient who suffered from fibromyalgia (FM). If the amount of pain is not maximal in the side more affected by parkinsonism and pain is not markedly relieved when the patient is in the "on" state, the pain may be due to FM.
PMID:
16828328
[PubMed - indexed for MEDLINE]



6.
Health News. 2005 Dec;11(12):11.
Parkinson's drug may relieve fibromyalgia pain.

[No authors listed]
PMID:
16419177
[PubMed - indexed for MEDLINE]
Related citations
Publication Types, MeSH Terms, Substances

7.
Z Rheumatol. 1998;57 Suppl 2:27-30.
Pathophysiology of akinetic movement disorders: a paradigm for studies in fibromyalgia?

Burgunder JM.
Source

Neurologische Poliklinik, Inselspital, Bern, Switzerland. jean-marc.burgunder@insel.ch
Abstract

Patients with fibromyalgia sometimes have sign of a movement disorder in addition to sensory disturbances sometimes similar as those found in akinetic syndromes. Akinesia is due to disturbances in the functions of the cortico-thalamo-nigro-striatal system and associated areas. The reason of this dysfunction in Parkinson's disease is a decreased nigral dopaminergic efferent innervation due to a neuronal degeneration in the pars compacta of the substantia nigra. Changes in other neurotransmitters, like GABA or serotonin, and in receptors and second messengers also occur, with additional modulation due to therapy. The aetiology of nigral malfunction is in only rarely known. Drugs and mutations of some genes are examples which give much insight in the pathogenesis of movement disorders in general. In other akinetic disorders, like multisystem atrophy, corticobasal ganglionic degeneration, and progressive supranuclear palsy, more complex patterns of degeneration have been found. This pathological anatomical disturbances have typical clinical effects which can be studied physiologically and with imaging in vivo. Since basal ganglia play also a role in pain, a comparative study of their involvement in movement disorders and nociception seems to be fruitful, especially in devising new therapeutic strategies.
PMID:
10025078
[PubMed - indexed for MEDLINE]
Related citations

Publication Types, MeSH Terms, Substances

8.
Altern Med Rev. 1998 Jun;3(3):187-98.
The detoxification enzyme systems.

Liska DJ.
Source

HealthComm International, Inc. P.O. Box 1729, Gig Harbor, WA 98335, USA. deann@healthcomm.com
Abstract

The human body is exposed to a wide array of xenobiotics in one s lifetime, from food components to environmental toxins to pharmaceuticals, and has developed complex enzymatic mechanisms to detoxify these substances. These mechanisms exhibit significant individual variability, and are affected by environment, lifestyle, and genetic influences. The scientific literature suggests an association between impaired detoxification and certain diseases, including cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction syndrome. Data regarding these hepatic detoxification enzyme systems and the body s mechanisms of regulating them suggests the ability to efficiently detoxify and remove xenobiotics can affect these and other chronic disease processes. This article reviews the myriad detoxification enzyme systems, their regulatory mechanisms, and the dietary, lifestyle, and genetic factors influencing their activities, as well as laboratory tests available to assess their functioning.
PMID:
9630736
[PubMed - indexed for MEDLINE]
Free full text
Related citations

Publication Types, MeSH Terms, Substances

9.
Ned Tijdschr Geneeskd. 1992 Jan 18;136(3):148.
[Chronic fatigue syndrome].

[Article in Dutch]
Horstink MW, Gonera EG, Berger HJ, van Weel C.
Comment on

• Ned Tijdschr Geneeskd. 1991 Oct 26;135(43):2005-9.

PMID:
1732849
[PubMed - indexed for MEDLINE]
Related citations
Publication Types, MeSH Terms

10.
Minerva Med. 1979 Mar 30;70(15):1093-8.
[Neurodystrophic rheumatism].

[Article in Italian]
Bianchi PG.
PMID:
312476
[PubMed - indexed for MEDLINE]
Related citations
MeSH Terms

11.
Clin Neuropharmacol. 2011 Jul 7. [Epub ahead of print]
Impulse Control Disorders Associated With Dopaminergic Medication in Patients With Pituitary Adenomas.

Martinkova J, Trejbalova L, Sasikova M, Benetin J, Valkovic P.
Source

*2nd Department of Neurology, Comenius University, Bratislava, Slovakia; †1st Department of Internal Medicine, and ‡Department of Neurology, Slovak Medical University, Bratislava, Slovakia; and §Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovakia.
Abstract

OBJECTIVE:

Impulse control disorders (ICDs) such as pathological gambling, compulsive shopping, compulsive eating, and hypersexuality are a matter of growing interest, especially in patients with Parkinson disease who are on dopamine replacement therapy. It was recently reported that ICDs are associated with other disorders also treated with dopaminergic drugs (dopamine agonists) such as restless legs syndrome, multiple system atrophy, progressive supranuclear palsy, and fibromyalgia. The aim of this study was to determine the prevalence of ICDs in patients with pituitary adenomas who take dopamine agonists (DAs).
METHODS:

Twenty consecutive patients with pituitary adenomas (mostly prolactinomas) taking DAs were assessed. All participated in a structured interview focused on ICDs, which was conducted by a physician.
RESULTS:

Two (10%) of 20 subjects had a condition diagnosed as ICD. The first patient is a 35-year-old man with giant macroprolactinoma who was alternately treated with different types of DAs (cabergoline, bromocriptine, and quinagolide). He developed compulsive eating and pathological gambling. The second patient is a 53-year-old man with macroprolactinoma who suffered from severe hypersexuality after cabergoline was begun.
CONCLUSIONS:

This study demonstrates the importance of systematic screening for ICDs in patients taking dopaminergic medication regardless of their primary condition.
PMID:
21738024
[PubMed - as supplied by publisher]
Related citations

13.
Reg Anesth Pain Med. 2010 May-Jun;35(3):294-303.
Duloxetine: a review of its pharmacology and use in chronic pain management.

Bellingham GA, Peng PW.
Source

Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Abstract

Duloxetine is a serotonin and norepinephrine reuptake inhibitor that possesses antidepressant and pain-relieving properties. Compared with other antidepressants, it has a high affinity for both norepinephrine and serotonin reuptake transporters, which are relatively balanced. Analgesic onset has been observed within the first week of administration in randomized controlled trials and is likely obtained by enhancing the tone of the descending pain inhibition pathways of the central nervous system. Randomized trials have documented significant analgesic effects for managing chronic pain associated with fibromyalgia and diabetic peripheral neuropathic pain. Studies have also suggested that pain associated with major depressive disorder can be reduced with this medication. Modest effects for headache, osteoarthritic pain, and pain secondary to Parkinson disease have also been documented, but data are obtained from single-blinded or open-label trials that require further corroboration with larger randomized studies. Duloxetine has not yet been directly compared with other antidepressants or anticonvulsants for the treatment of pain syndromes.
PMID:
20921842
[PubMed - indexed for MEDLINE]



17.
J Gambl Stud. 2009 Sep;25(3):425-31. Epub 2009 Feb 25.
Impulse control disorder behaviors associated with pramipexole used to treat fibromyalgia.

Holman AJ.
Source

Pacific Rheumatology Research, 4300 Talbot Road South, Suite 101, Renton, WA, 98055, USA. AJHSeattle@aol.com
Abstract

OBJECTIVE:

Compulsivity has been associated with use of dopamine agonists used to treat Parkinson's disease (PD). Increasing use of these agents to treat fibromyalgia (FM) raises concern for this unexpected toxicity in a new group of patients. This is the first report of compulsive gambling and shopping among patients taking dopamine agonists for treatment of FM.
DESIGN:

A retrospective chart review of all patients in a large, active FM research practice was used to identify compulsivity associated with dopamine agonists and describe its remission following dug withdrawal.
RESULTS:

Of 3006 patients with FM treated between 2002 and 2006, 1356 had taken > or =1 dose of a dopamine agonist ( >95% pramipexole). Twenty-one (3 male, 18 female) were identified with compulsive gambling (33%), shopping (40%) or both (27%) after taking a 4.5 mg mean dose of pramipexole at bedtime for 14.4 +/- 14.9 months. Compulsivity resolved in 3-10 days for 19 of 21 patients and by 3 months for all following a monitored, compulsory tapered discontinuation over 7 days.
CONCLUSIONS:

While biologic aspects of PD and FM differ considerably, compulsive gambling and shopping have become important, yet unexpected concerns related to use of dopamine agonists for patients with FM and their treating clinicians.
PMID:
19241148
[PubMed - indexed for MEDLINE]
Related citations





20.
Expert Rev Neurother. 2008 May;8(5):781-97.
Role of central dopamine in pain and analgesia.

Wood PB.
Source

Angler Biomedical Technologies, LLC, 18401 Reed Parks Road, Jonestown, TX 78645, USA. pwood@anglerbiomedical.com
Abstract

Recent insights have demonstrated a central role for dopaminergic neurotransmission in modulating pain perception and natural analgesia within supraspinal regions, including the basal ganglia, insula, anterior cingulate cortex, thalamus and periaqueductal gray. In addition, while the participation of serotonin and norepinephrine in spinal descending inhibition of pain is well known, a critical role for dopamine in descending inhibition has also been demonstrated. Decreased levels of dopamine likely contribute to the painful symptoms that frequently occur in Parkinson's disease. Moreover, abnormalities in dopaminergic neurotransmission have been objectively demonstrated in painful clinical conditions, including burning mouth syndrome, fibromyalgia and restless legs syndrome. Evidence from animal models and indirect evidence from pharmaceutical trials also suggest a role for dopamine in chronic regional pain syndrome and painful diabetic neuropathy. Several novel classes of medication with analgesic properties have bearing on dopaminergic activity as evident in the capacity of dopamine antagonists to attenuate their analgesic capacity. An expanded appreciation for the role of dopamine in natural analgesia provides the impetus for further study involving preclinical models and advanced neuroimaging techniques in humans, which may lead to the development of novel therapeutic strategies.
PMID:
18457535
[PubMed - indexed for MEDLINE]


21.
Brain Res Rev. 2007 Dec;56(2):346-61. Epub 2007 Aug 28.
The use of tDCS and CVS as methods of non-invasive brain stimulation.

Been G, Ngo TT, Miller SM, Fitzgerald PB.
Source

Alfred Psychiatry Research Centre, The Alfred Hospital and Monash University School of Psychology, Psychiatry and Psychological Medicine, Commercial Rd, Melbourne, VIC 3004, Australia.
Abstract

Transcranial direct current stimulation (tDCS) and caloric vestibular stimulation (CVS) are safe methods for selectively modulating cortical excitability and activation, respectively, which have recently received increased interest regarding possible clinical applications. tDCS involves the application of low currents to the scalp via cathodal and anodal electrodes and has been shown to affect a range of motor, somatosensory, visual, affective and cognitive functions. Therapeutic effects have been demonstrated in clinical trials of tDCS for a variety of conditions including tinnitus, post-stroke motor deficits, fibromyalgia, depression, epilepsy and Parkinson's disease. Its effects can be modulated by combination with pharmacological treatment and it may influence the efficacy of other neurostimulatory techniques such as transcranial magnetic stimulation. CVS involves irrigating the auditory canal with cold water which induces a temperature gradient across the semicircular canals of the vestibular apparatus. This has been shown in functional brain-imaging studies to result in activation in several contralateral cortical and subcortical brain regions. CVS has also been shown to have effects on a wide range of visual and cognitive phenomena, as well as on post-stroke conditions, mania and chronic pain states. Both these techniques have been shown to modulate a range of brain functions, and display potential as clinical treatments. Importantly, they are both inexpensive relative to other brain stimulation techniques such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS).
PMID:
17900703
[PubMed - indexed for MEDLINE]
Related citations

Publication Types, MeSH Terms

22.
Scand J Rheumatol Suppl. 2004;119:12-8.
Spectrum of use and tolerability of 5-HT3 receptor antagonists.

Haus U, Späth M, Färber L.
Source

Novartis Pharma GmbH, Nuremberg, Germany. ulrike.haus@pharma.novartis.com
Abstract

Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.






Prevalence, classification, and etiology of pain in Parkinson's disease: association between Parkinson's disease and fibromyalgia or chronic widespread pain.

Toda K, Harada T.
Source

Department of Rehabilitation, Hatsukaichi Memorial Hospital, Hiroshima, Japan. goutattack@yahoo.co.jp
Abstract

Parkinson's disease (PD) is characterized by resting tremor, slow and decreased movement (hypokinesia and akinesia), rigidity, postural instability, problems with gait, and coordination. The prevalence of PD is between 0.1% and 0.3% in the general population and between 1% and 2% in persons 65 years of age or older. Patients with PD are more likely to suffer from pain. Indeed, the chief complaint of patients with severe motor disturbance and severe pain is pain rather than motor disturbance. Fibromyalgia (FM) is defined by widespread pain (pain in the left and right sides of the body, pain above the waist, pain below the waist, and axial skeletal pain) for more than 3 months and the presence of at least 11 of the 18 specified tender points. FM and chronic widespread pain (CWP), which is usually an incomplete form of FM, cause pain in the musculoskeletal region, but their etiologies are unknown. Therefore, it is almost impossible to determine whether or not pain in the musculoskeletal region is in the musculoskeletal origin. We suspect that dysfunction or degeneration of the nerves that control pain, mind, and movement in the brain causes FM, depression, and PD, respectively. When pain in PD is discussed, FM and CWP should be considered because their prevalence is high. Patients with PD may be likely to suffer from FM and CWP; however, the prevalence of FM and CWP in patients with PD has not been reported. Here, we discuss the relationship between PD and FM or CWP.
PMID:
20805678
[PubMed - indexed for MEDLINE]
Free full text
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Mayo Clin Proc. 2009 Feb;84(2):134-8.
Clinical and genetic description of a family with a high prevalence of autosomal dominant restless legs syndrome.

Young JE, Vilariño-Güell C, Lin SC, Wszolek ZK, Farrer MJ.
Source

Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.
Abstract

OBJECTIVE:

To conduct clinical and molecular genetic analyses of the members of an extended family in Central Indiana with a high prevalence of restless legs syndrome (RLS).
PARTICIPANTS AND METHODS:

From February 1, 2006, through August 31, 2008, we collected data from members of this family, which is of English descent. Genealogical methods were used to expand the family tree, and family members were screened with an RLS questionnaire. Telephone interviews and personal examinations were performed at Mayo Clinic and during a field trip to Central Indiana. Blood samples were collected for molecular genetic analysis. A follow-up telephone interview was conducted 1 year later.
RESULTS:

The family tree spans 7 generations with 88 living members, 30 of whom meet the criteria for diagnosis of RLS established by the International Restless Legs Syndrome Study Group. Three affected family members also have Parkinson disease or essential tremor. The mode of RLS inheritance is compatible with an autosomal dominant pattern. The affected family members do not exhibit linkage to the 5 known RLS loci or mutations in the RLS susceptibility genes MEIS1 and BTBD9.
CONCLUSION:

Of 88 members of this single extended family in Central Indiana, 30 were diagnosed as having RLS. Because our analysis shows that the disease is not linked to any of the known RLS loci or risk-associated genes, we postulate that members of this family may carry a gene mutation in a novel genetic locus.
PMID:
19181647
[PubMed - indexed for MEDLINE]
PMCID: PMC2664577
Free PMC Article


3.
Mol Nutr Food Res. 2008 Jul;52(7):780-8.
Medication-induced mitochondrial damage and disease.

Neustadt J, Pieczenik SR.
Source

Montana Integrative Medicine, Bozeman, MT 59718, USA. drneustadt@gmail.com
Abstract

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health and disease. Damage to mitochondria is now understood to play a role in the pathogenesis of a wide range of seemingly unrelated disorders such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis. Medications have now emerged as a major cause of mitochondrial damage, which may explain many adverse effects. All classes of psychotropic drugs have been documented to damage mitochondria, as have stain medications, analgesics such as acetaminophen, and many others. While targeted nutrient therapies using antioxidants or their precursors (e. g., N-acetylcysteine) hold promise for improving mitochondrial function, there are large gaps in our knowledge. The most rational approach is to understand the mechanisms underlying mitochondrial damage for specific medications and attempt to counteract their deleterious effects with nutritional therapies. This article reviews our basic understanding of how mitochondria function and how medications damage mitochondria to create their occasionally fatal adverse effects.
PMID:
18626887
[PubMed - indexed for MEDLINE]
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4.
Exp Mol Pathol. 2007 Aug;83(1):84-92. Epub 2007 Jan 18.
Mitochondrial dysfunction and molecular pathways of disease.

Pieczenik SR, Neustadt J.
Source

drneustadt@gmail.com
Abstract

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health, disease, and aging. A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis, have underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production, the accumulation of mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction. Antioxidant therapies hold promise for improving mitochondrial performance. Physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them. If in the next 50 years advances in mitochondrial treatments match the immense increase in knowledge about mitochondrial function that has occurred in the last 50 years, mitochondrial diseases and dysfunction will largely be a medical triumph.
PMID:
17239370
[PubMed - indexed for MEDLINE]
Parkinsonism Relat Disord. 2007 Jul;13(5):312-4. Epub 2006 Jul 7.
Parkinson disease patient with fibromyalgia: a case report.

Toda K, Harada T, Ishizaki F, Horie N, Yamada T.
Source

Department of Rehabilitation, Hiroshima Prefectural Rehabilitation Center, 295-3 Taguchi, Saijyou, Higashi-Hiroshima, Hiroshima 739-0036, Japan. goutattack@yahoo.co.jp
Abstract

Parkinson's disease (PD) is characterized by motor disturbances such as tremor, slow movement and rigidity. Also, pain is a common symptom in patients with PD. The prevalence of pain is 40-75% in patients with PD. Physicians should pay attention to pain in patient with PD. We report a PD patient who suffered from fibromyalgia (FM). If the amount of pain is not maximal in the side more affected by parkinsonism and pain is not markedly relieved when the patient is in the "on" state, the pain may be due to FM.
PMID:
16828328
[PubMed - indexed for MEDLINE]



6.
Health News. 2005 Dec;11(12):11.
Parkinson's drug may relieve fibromyalgia pain.

[No authors listed]
PMID:
16419177
[PubMed - indexed for MEDLINE]
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Publication Types, MeSH Terms, Substances

7.
Z Rheumatol. 1998;57 Suppl 2:27-30.
Pathophysiology of akinetic movement disorders: a paradigm for studies in fibromyalgia?

Burgunder JM.
Source

Neurologische Poliklinik, Inselspital, Bern, Switzerland. jean-marc.burgunder@insel.ch
Abstract

Patients with fibromyalgia sometimes have sign of a movement disorder in addition to sensory disturbances sometimes similar as those found in akinetic syndromes. Akinesia is due to disturbances in the functions of the cortico-thalamo-nigro-striatal system and associated areas. The reason of this dysfunction in Parkinson's disease is a decreased nigral dopaminergic efferent innervation due to a neuronal degeneration in the pars compacta of the substantia nigra. Changes in other neurotransmitters, like GABA or serotonin, and in receptors and second messengers also occur, with additional modulation due to therapy. The aetiology of nigral malfunction is in only rarely known. Drugs and mutations of some genes are examples which give much insight in the pathogenesis of movement disorders in general. In other akinetic disorders, like multisystem atrophy, corticobasal ganglionic degeneration, and progressive supranuclear palsy, more complex patterns of degeneration have been found. This pathological anatomical disturbances have typical clinical effects which can be studied physiologically and with imaging in vivo. Since basal ganglia play also a role in pain, a comparative study of their involvement in movement disorders and nociception seems to be fruitful, especially in devising new therapeutic strategies.
PMID:
10025078
[PubMed - indexed for MEDLINE]
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Publication Types, MeSH Terms, Substances

8.
Altern Med Rev. 1998 Jun;3(3):187-98.
The detoxification enzyme systems.

Liska DJ.
Source

HealthComm International, Inc. P.O. Box 1729, Gig Harbor, WA 98335, USA. deann@healthcomm.com
Abstract

The human body is exposed to a wide array of xenobiotics in one s lifetime, from food components to environmental toxins to pharmaceuticals, and has developed complex enzymatic mechanisms to detoxify these substances. These mechanisms exhibit significant individual variability, and are affected by environment, lifestyle, and genetic influences. The scientific literature suggests an association between impaired detoxification and certain diseases, including cancer, Parkinson's disease, fibromyalgia, and chronic fatigue/immune dysfunction syndrome. Data regarding these hepatic detoxification enzyme systems and the body s mechanisms of regulating them suggests the ability to efficiently detoxify and remove xenobiotics can affect these and other chronic disease processes. This article reviews the myriad detoxification enzyme systems, their regulatory mechanisms, and the dietary, lifestyle, and genetic factors influencing their activities, as well as laboratory tests available to assess their functioning.
PMID:
9630736
[PubMed - indexed for MEDLINE]
Free full text
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Publication Types, MeSH Terms, Substances

9.
Ned Tijdschr Geneeskd. 1992 Jan 18;136(3):148.
[Chronic fatigue syndrome].

[Article in Dutch]
Horstink MW, Gonera EG, Berger HJ, van Weel C.
Comment on

• Ned Tijdschr Geneeskd. 1991 Oct 26;135(43):2005-9.

PMID:
1732849
[PubMed - indexed for MEDLINE]
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Publication Types, MeSH Terms

10.
Minerva Med. 1979 Mar 30;70(15):1093-8.
[Neurodystrophic rheumatism].

[Article in Italian]
Bianchi PG.
PMID:
312476
[PubMed - indexed for MEDLINE]
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MeSH Terms

11.
Clin Neuropharmacol. 2011 Jul 7. [Epub ahead of print]
Impulse Control Disorders Associated With Dopaminergic Medication in Patients With Pituitary Adenomas.

Martinkova J, Trejbalova L, Sasikova M, Benetin J, Valkovic P.
Source

*2nd Department of Neurology, Comenius University, Bratislava, Slovakia; †1st Department of Internal Medicine, and ‡Department of Neurology, Slovak Medical University, Bratislava, Slovakia; and §Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovakia.
Abstract

OBJECTIVE:

Impulse control disorders (ICDs) such as pathological gambling, compulsive shopping, compulsive eating, and hypersexuality are a matter of growing interest, especially in patients with Parkinson disease who are on dopamine replacement therapy. It was recently reported that ICDs are associated with other disorders also treated with dopaminergic drugs (dopamine agonists) such as restless legs syndrome, multiple system atrophy, progressive supranuclear palsy, and fibromyalgia. The aim of this study was to determine the prevalence of ICDs in patients with pituitary adenomas who take dopamine agonists (DAs).
METHODS:

Twenty consecutive patients with pituitary adenomas (mostly prolactinomas) taking DAs were assessed. All participated in a structured interview focused on ICDs, which was conducted by a physician.
RESULTS:

Two (10%) of 20 subjects had a condition diagnosed as ICD. The first patient is a 35-year-old man with giant macroprolactinoma who was alternately treated with different types of DAs (cabergoline, bromocriptine, and quinagolide). He developed compulsive eating and pathological gambling. The second patient is a 53-year-old man with macroprolactinoma who suffered from severe hypersexuality after cabergoline was begun.
CONCLUSIONS:

This study demonstrates the importance of systematic screening for ICDs in patients taking dopaminergic medication regardless of their primary condition.
PMID:
21738024
[PubMed - as supplied by publisher]
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13.
Reg Anesth Pain Med. 2010 May-Jun;35(3):294-303.
Duloxetine: a review of its pharmacology and use in chronic pain management.

Bellingham GA, Peng PW.
Source

Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Abstract

Duloxetine is a serotonin and norepinephrine reuptake inhibitor that possesses antidepressant and pain-relieving properties. Compared with other antidepressants, it has a high affinity for both norepinephrine and serotonin reuptake transporters, which are relatively balanced. Analgesic onset has been observed within the first week of administration in randomized controlled trials and is likely obtained by enhancing the tone of the descending pain inhibition pathways of the central nervous system. Randomized trials have documented significant analgesic effects for managing chronic pain associated with fibromyalgia and diabetic peripheral neuropathic pain. Studies have also suggested that pain associated with major depressive disorder can be reduced with this medication. Modest effects for headache, osteoarthritic pain, and pain secondary to Parkinson disease have also been documented, but data are obtained from single-blinded or open-label trials that require further corroboration with larger randomized studies. Duloxetine has not yet been directly compared with other antidepressants or anticonvulsants for the treatment of pain syndromes.
PMID:
20921842
[PubMed - indexed for MEDLINE]

• A retrospective chart review of all patients in a large, active FM research practice was used to identify compulsivity associated with While biologic aspects of PD and FM differ considerably, compulsive gambling and shopping have become important, yet unexpected concerns related to use of dopamine agonists for patients with FM and their treating clinicians.

PMID:
19241148
[PubMed - indexed for MEDLINE]