I have wrote a simple and easy to read abstract study-like about fibrosis, tos and neurogenic inflammation and ptx+ vit E with references.


Perineural and muscle fibrosis play a large role in TOS (1,2). In regards to others fibrotic deseases, this fibrosis don't seem to be different from others inflammation-induced fibrosis (3, 3b, 4) In fact, all fibrosis are driven by inflammation (5)

Inflammation are driven mostly by citokynes (with growth factors) and neuropeptides (6)

Mast cell and endothelial stabilizer, neuropeptides and cytokines inhibitors have been suggested as a treatment for TOS (3)

"It must be primarily neural involving sensitized nervi-nervorum and communicating with local mast cells, monocytes, and fibroblasts to participate in the micro-inflammatory process that drives the pathology. This involves not only inflammation, but also the accompanying growth factors, which affect nerves, muscles (hence, the frequent scalene hypertrophy), existing fibrosis, (...) to produce the insidious, cumulative, and devastating symptoms typical of NTOS."

"the closest analogous description that I could find in the literature was that of painful hypertrophic scarring, which showed a similar inflammatory neuropeptide distribution and an abundance of growth factors that were also pro-inflammatory (NGF, FGF…), at least in part. "(6a)

This definitely confirm the role of neurogenic inflammation (NI) and his fibrosis in TOS. NI may lead to neuronal disfunction as well.

All fibrosis are similar, however they are specificities in some organs to take into account (7)

In addition, hypertrophy of scalene may be caused directly by this chronic inflammation neuronale (7aa)

"These findings support that focal nerve inflammation is sufficient to cause neuronal discharge changes that are consistent with clinical findings in early CRPS"


Inhibition of the pathways regulated by CTGF*, IGF-1, VEGF,(b)FGF(2)*, PDGF* and TGF-b*, ET-1* and antioxidants have been suggested to provide novel therapeutic approaches for the treatment of fibrosis (7a)(7b)

Evidences

pentoxifylline (PTX) + Vitamin E for TOS :

PTX

- Inhibit inflammatory and fibrogenic citokynes (8)

- Stabilize endothelial (8)

- Reverse peri-neural and post-operative fibrosis, same as TOS fibrosis (9)

- Inhib neuropeptides substance P, PDCF CTGF (8)

- Inhib some "hypertrophic" growth factors : fgf2, et-1 (8)

- Improve blood flow

- Improve oxygenation of tissues

- Prevent clots

- Antioxidant

- Well tolerated at long terme, Only 3-7% stop the drug because side effects (10)

Vitamin e

- defiency linked to more scar
- increase lipid peroxidation
- anti oxidant
- Blood thinner
- Well tolerated

Having a generally healthy life may increase significantly the benefits (anti oxidant et anti inflammatory), no sugar, good sleep.


References :

1 The anterior scalene muscle in thoracic outlet compression syndrome. Histochemical and morphometric studies
http://www.ncbi.nlm.nih.gov/pubmed/3767646

2 Scalene muscle abnormalities in traumatic thoracic outlet syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/2301718

3 THORACIC OUTLET SYNDROME AS A DISORDER OF NEUROGENIC INFLAMMATION
http://www.doctorellis.com/TOS_neurogenic.html

3b TGF-β1 and radiation fibrosis: a master switch and a specific therapeutic target?
http://www.redjournal.org/article/S0...435-1/abstract

4 Pulmonary fibrosis: cytokines in the balance
http://erj.ersjournals.com/content/11/6/1218.full.pdf

5 Cell Injury, Repair, Fibrosis, and Inflammation
http://www2.niddk.nih.gov/Research/S...Liver/IRFI.htm

6 CYTOKINES IN ACUTE AND CHRONIC INFLAMMATION
http://immuneweb.xxmu.edu.cn/ckine-infec.pdf

6a USE OF NEUROPROTECTIVE ADJUNCTS IN NEUROGENIC THORACIC-OUTLET SYNDROME
http://www.doctorellis.com/Lecture.html

7 Current management for late normal tissue injury: radiation-induced fibrosis and necrosis.
http://www.ncbi.nlm.nih.gov/pubmed/17395040

7aa Focal nerve inflammation induces neuronal signs consistent with symptoms of early complex regional pain syndromes
http://cat.inist.fr/?aModele=afficheN&cpsidt=21896157

7a Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis
http://erj.ersjournals.com/content/29/5/976.full.pdf

7b Antioxidants as potential therapeutics for lung fibrosis
http://www.ncbi.nlm.nih.gov/pubmed/17999627

8 Pentoxifylline in the Treatment of Radiation-Induced Fibrosis
http://jco.ascopubs.org/content/22/11/2207.full

9 Post-operative fibrosis: Pathophysiological aspects and therapeutical perspectives
http://www.sciencedirect.com/science

10 Pentoxifylline side effects
http://www.drugs.com/sfx/pentoxifyll...e-effects.html


And the best : I am on ptx + vit E since 12 days, and i have relief from maybe anti inflammatory effect and blood thinner

No side effect if taken during meal - for the moment.

what dose vitamin e? what is ptx?

Haven't read any of these yet - but it has info on PTX

[Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti-inflammatory effects. Currently, PTX is approved by the Food and Drug ...]
http://www.google.com/search?q=pento...ient=firefox-a

1000 iu tocopherol, 800mg ptx

Update :

Summary :

I Neurogenic inflammation and fibrosis in TOS
A) General
B) Description of tos's fibrosis

II Scalenes hypertrophy, neuronal inflammation and growth factors

III Treatment goal : reducing fibrosis and neurogenic inflammation
A) pentoxifylline (PTX) + Vitamin E
B) pentoxifylline (PTX) + Vitamin E + clodronate (later)

Conclusion


-------------------------------------------------


I Neurogenic inflammation and fibrosis in TOS

A) General

Perineural and muscle fibrosis play a large role in TOS (1,2). In regards to others fibrotic deseases, this fibrosis don't seem to be different from others inflammation-induced fibrosis (3, 3b, 4) In fact, all fibrosis are driven by inflammation (5)

Inflammation are driven mostly by citokynes (with their growth factors) and neuropeptides (6)

The role of neurogenic inflammation (NI) and his fibrosis in TOS is cleary determined (3). NI may lead to neuronal disfunction.

Mast cell and endothelial stabilizer, neuropeptides and cytokines inhibitors, all part of neurogenic inflammation have been suggested as a treatment for TOS (3)

Hyperbaric oxygen and curcumin have been used for TOS with some success (references lost). They are anti inflammatory and antifibrotic.

All fibrosis are similar and induced by inflammation, however they are specificities in some organs and underlying desease to take into account (7)



B) Description of tos's fibrosis

Doctor ellis, specialist of TOS, describe the process here :

"It must be primarily neural involving sensitized nervi-nervorum - primilary by tnfa - and communicating with local mast cells, monocytes, and fibroblasts to participate in the micro-inflammatory process that drives the pathology. This involves not only inflammation, but also the accompanying growth factors, which affect nerves, muscles (hence, the frequent scalene hypertrophy), existing fibrosis, (...) to produce the insidious, cumulative, and devastating symptoms typical of NTOS."

And what the fibrosis look like :

"The epi- or perineural fibrotic scar that the vascular surgeon was removing, however, turned out to be pharmacologically very active with multiple pro-inflammatory neuropeptides [...]"


"the closest analogous description that I could find in the literature was that of painful hypertrophic scarring, which showed a similar inflammatory neuropeptide distribution and an abundance of growth factors that were also pro-inflammatory (NGF, FGF…), at least in part. "(6a)



II ) Scalenes hypertrophy, neuronal inflammation and growth factors.

The second cause of TOS is muscle change with hypertrophy. There are numbers of explanations for this. One recent is neuronal discharge of nerve fibers, increasing tone and leading to hypertrophy.

Chronic increased tone induced by inflammatory nerve fibers can explain the scalene's hypertrophy.

Scalenes of tos'er are very adaptive as we can see when fibers's hypertrophy reverse after tenotomy (2)

Focal nerve inflammation is sufficient to cause neuronal discharge changes that are consistent with clinical findings in early CRPS (7aa)

Studies shows that perineural inflammation with no axonal nerve damage around the nerve trunk elevates spontaneous activity and induces mechanosensitivity in myelinated axons.(7aa , second link)

Sympathetic ganglion, axons and neurites are affected in tos (3)

Tnfa, IGF-1 and others growth factors may be involved (8a)



III) Treatment goal : reducing fibrosis and neurogenic inflammation


Inhibition of the pathways regulated by pro-inflammatory neuropeptides and cytokines CTGF*, IGF-1, VEGF,(b)FGF(2)*, PDGF* and TGF-b*, ET-1* and antioxidants have been suggested to provide novel therapeutic approaches for the treatment of fibrosis (7a)(7b)



A) pentoxifylline (PTX) + Vitamin E


PTX

- Inhibit inflammatory and fibrogenic citokynes (8)

- Stabilize endothelial (8)

- Reverse peri-neural and post-operative fibrosis and RIF same as TOS fibrosis (9)

- Inhib neuropeptides substance P, PDCF CTGF (8)

- Inhib some "hypertrophic" growth factors : fgf2, et-1 (8)

- Improve blood flow

- Improve oxygenation of tissues

- Prevent clots

- Antioxidant

- Well tolerated at long terme, Only 3-7% stop the drug because side effects (10)

Vitamin e

- defiency linked to more scar
- increase lipid peroxidation
- anti oxidant
- Blood thinner
- Well tolerated


Conclusion : TOS is primilary maintened neurogenic inflammation by fibrosis affecting neurites and scalenes.
This type of fibrosis can be reversed by pentoxifylline associated with tocopherol, so it have potential curative effects in TOS.


References :

1 The anterior scalene muscle in thoracic outlet compression syndrome. Histochemical and morphometric studies
http://www.ncbi.nlm.nih.gov/pubmed/3767646

2 Scalene muscle abnormalities in traumatic thoracic outlet syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/2301718

3 THORACIC OUTLET SYNDROME AS A DISORDER OF NEUROGENIC INFLAMMATION
http://www.doctorellis.com/TOS_neurogenic.html

3b TGF-ß1 and radiation fibrosis: a master switch and a specific therapeutic target?
http://www.redjournal.org/article/S0...435-1/abstract

4 Pulmonary fibrosis: cytokines in the balance
http://erj.ersjournals.com/content/11/6/1218.full.pdf

5 Cell Injury, Repair, Fibrosis, and Inflammation
http://www2.niddk.nih.gov/Research/S...Liver/IRFI.htm

6 CYTOKINES IN ACUTE AND CHRONIC INFLAMMATION
http://immuneweb.xxmu.edu.cn/ckine-infec.pdf

6a USE OF NEUROPROTECTIVE ADJUNCTS IN NEUROGENIC THORACIC-OUTLET SYNDROME
http://www.doctorellis.com/Lecture.html

7 Current management for late normal tissue injury: radiation-induced fibrosis and necrosis.
http://www.ncbi.nlm.nih.gov/pubmed/17395040

7aa Focal nerve inflammation induces neuronal signs consistent with symptoms of early complex regional pain syndromes
http://cat.inist.fr/?aModele=afficheN&cpsidt=21896157
Inflammation with no axonal damage of the rat saphenous nerve trunk induces ectopic discharge and mechanosensitivity in myelinated axons
http://cat.inist.fr/?aModele=afficheN&cpsidt=1092554

7a Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis
http://erj.ersjournals.com/content/29/5/976.full.pdf

7b Antioxidants as potential therapeutics for lung fibrosis
http://www.ncbi.nlm.nih.gov/pubmed/17999627

8 Pentoxifylline in the Treatment of Radiation-Induced Fibrosis
http://jco.ascopubs.org/content/22/11/2207.full

8a Bimodal effects of TNF-α on differentiation and hypertrophy of skeletal muscle cell cultures
http://www.bio.unipd.it/bam/PDF/16-5&6/Moresi.pdf

9 Post-operative fibrosis: Pathophysiological aspects and therapeutical perspectives
http://www.sciencedirect.com/science

10 Pentoxifylline side effects
http://www.drugs.com/sfx/pentoxifyll...e-effects.html

Boytos.


Next step is to list all fibrotics/anti NI agents and their functions, influence of vitamin in the process, and improving neuronal function is a safe way.

Soluble TNF-α receptors and pentoxifylline, a TNF-α inhibitor, partially restored neuronal differentiation

http://neurotalk.psychcentral.com/sh...814#post740814