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Cranial Electrotherapy Stimulation (CES)

Essential fatty acids (EFAs)

CHART of significant eicosanoids and their effects

CHART of specific / significant eicosanoids and their effects

To learn the basics of eicosanoids:

"Local Hormones" (Eicosanoids) - Cell's "First Response" team -  Mediators of inflammation / pain, blood pressure, blood clotting, tissue repair . . .

Meet the VIP eicosanoid families and their members

The eicosanoid families

•  The PROSTAGLANDIN family:   (produced in most cells)

Series 1 (PGE1) and Series 3 prostaglandins. Counter inflammation

Series 2 prostaglandins.   Significant ones are PGD2, PGE2, PGF2α, PGI2 (a.k.a. prostacyclin. a potent vasodilator produced mainly by endothelial cells, which comprise the inner lining of blood and lymphatic vessels, and epithelial cells lining the inside of other hollow organs e.g. bronchial epithelial cells in airways, and the skin's epidermis.

•  The THROMBOXANE family:   (produced mainly in platelets, also placenta, lungs) Mainly thromboxane TXA2. Promotes blood clotting /platelet-aggregation and is a potent vasoconstrictor. Also broncho-constrictive.

•  The LEUKOTRIENE family:  Produced in leukocytes.  i.e. white blood cells:  Series 4 and Series 5 leukotrienes

•  The EOXIN family:  Produced in immune system eosinophils (white blood cells), mast cells, and some other tissues. Generally steps up inflammatory response.

•  The LIPOXIN and RESOLVIN families: Deal with reducing excessive tissue injury and  the resolution of inflammation.

 LIPOXINS ( Produced in platelets, neutrophils, red blood cells and reticulocytes; also by low dose aspirin).

RESOLVINS (Produced in most cells) Potent anti-inflammatory agents that as their name suggests,  resolve inflammation. They limit the extent of inflammation by blocking the actions of inflammatory prostanoids (prostaglandins and thromboxanes) and also clear away breakdown products of inflammation process. E.g. RVD1-6

•  The PROTECTIN family 

Eicosanoid activity is complex

Each family member has specific functions.   However, their activity can be confusing, since their tissue location, and which enzyme produced them can sometimes determine whether they either promote or resolve inflammation.

Dietary omega-3 EPA and omega-6 GLA counter the predominately inflammatory effects of omega-6 AA in three ways:

•   Competitive inhibition.   DGLA and EPA compete with AA for COX and LOX enzymes, such that the presence of DGLA and also EPA in tissues lowers the production of AA's eicosanoids

•   Displacement.   Increased dietary omega-3 results in decreased AA in brain and other tissue.  Green et al, 2005

•   Direct counteraction.   Some DGLA and EPA-derived eicosanoids counteract their AA derived counterparts.   E.g.  PGE1 derived from DGLA acts against PGE2 derived from AA.

COX enzymes

 COX-1 - "The housekeeper"

 COX-1 is expressed constitutively in most tissues and regulates basal levels of prostaglandins to maintain general homeostasis.   Only COX-1 produces prostaglandins that protect the stomach and intestinal lining.

 COX-1 is also actively involved in certain  traumatic/stimulated events.    Only COX-1 produces prostaglandins that activate platelets and constrict airways.

The human COX-1 gene is located on chromosome 9

 COX-2 - "The main activator"

COX-2 enzyme is mostly induced in "times of trouble".  Responsible for releasing PROSTAGLANDINS after an infection, injury, or in cancer development, COX-2 expression is induced by the cytokines interleukin (IL)-1, IL-2, and TNF, as well as by lipopolysaccharide (LPS) produced by Gram-negative bacteria.  Kang et al, 2007

COX-2 enzyme inhibitors reduce the prostanoids PGI2, PGD2, PGE2 PGF2α, and thromboxane A2

The human COX-2 gene is located on chromosome 1

Traditional NSAIDs (e.g. aspirin, Aleve, Motrin) suppress both COX-1 and COX-2 enzymes

Cox 1 and 2 inhibitor effects on eicosonoids

NSAIDS (Cox enzyme inhibitors / Coxibs) - Anti-inflammatory drugs WARNING!

To help understand the effects of eicosanoids, this website color-codes their families and their members by their overall function.  Their activities can not be differentiated as "good" and "bad".   E.g. promoting inflammation is very necessary to aid repair, if say you've been injured, but can be overly painful and damage tissue if done to excess, or causing the blood to clot can be life-saving if you just cut yourself, but can cause a heart attack if overdone in the arteries, and lastly, cell-proliferation is needed to repair tissue, but when out of control can cause a tumor. Excessive or unresolved inflammation, or overreaction to stimuli can lead to uncontrolled tissue damage and health problems

 "Orange"  represents activity altering the status quo, some increasing inflammation.

 "Turqoise" represents more of a "calming down" / going-back-to-normal action and/or resolving the inflammation.

Chart of significant eicosanoids and their effects
(Currently adding to this list)
Prostanoids: Prostaglandins (produced in most cells)
 and Thromboxanes via COX-1 (housekeeping) and COX-2 (mostly induced under stress conditions) enzymes
PGE1 
Derived directly from: Omega-6 DGLA (in mother's milk). Derived indirectly with the sufficient presence of omega-3 EPA from: Omega-6 LA (E.g. in nuts, seeds, vegetable oils, grass-fed animal fats or legumes,  or from GLA (E.g. in borage /evening primrose oil),
Released area Action Information
All cells ice cube

Counters inflammation

jumping painfree joy

Reduces pain

Sesame lignans promote conversion of omega-6 DGLA to anti-inflammatory PGE1 in favor of pro-inflammatory omega-6 AA
Blood vessels vasodilation effects

Vasodilation

normal_bp

Normalize BP

 
Immune System cells

Immune System IncreaseEnhance immune response

 
Bronchial
airways
Constricted  airway

Bronchodilation

     
PGD2
Derived from omega-6 AA mostly (in the Western diet) from meat and eggs; inhibited by omega-3 EPA presence;
PGD2 is a major prostaglandin produced by immune system (IS) mast cells (contain histamine and the anticoagulant heparin).   Recruits T-helper (CD4) cells (important in adaptive IS), eosinophils (a type of white blood cell (WBC) that aids IS combat against multicellular parasites and other infections), basophils (another WBC granulocyte responsible for inflammatory reactions during an immune response, and in the formation of acute and chronic allergic diseases). 
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Mast cells in Airways;

Macrophages;
Constricted  airway

Potent bronchoconstrictor

Involved in allergic rhinitis and allergic bronchial asthma. Atttracts neutrophils (WBCs that fight infection and heal injuries). Involved in late phase reactions to allergens (6 hrs after exposure).  PGD2 has 10 times higher concentration in asthma patients compared to control patients.
Mast cells in PULMONARY and PLACENTAL blood vessels vasoconstriction

Potent vasoconstrictor

PGD2 is a potent vasoconstrictor via thromboxane/endoperoxide (TX/E) receptor activation in pulmonary vessels, but this mechanism is not responsible for vasoconstriction in systemic vessels or in airway. King, 1991
Mast cells in UTERINE blood vessels vasodilation effects

Vasodilation

PGD2 can promote mild vasodilation if TX/E is blocked.  King, 1991
PGD2 dilates uterine blood vessels. Together with its ability to constrict placental blood vessels, it may control utero-placental blood flow.
Mast cells in brain
brain
  In mamalian organs, large amounts of PGD2 are found only in the brain (and in mast cells)
Mast cells in skin vasodilation effects

Vasodilation

 
PGD2 is the primary mediator of vasodilation after taking niacin (vitamin B3) - the so-called "niacin flush".
Involved in urticuria (hives), and balding
- a causal link was found between elevated levels of localized PGD2 and hair growth inhibition (by increasing Prostaglandin D2 synthase). Garza et al, 2012.
PGE2

Derived from omega-6 AA mostly (in the Western diet) from meat and eggs; inhibited by omega-3 EPA presence;
PGE2 promotes tumor growth.   PGE2 is the most abundant prostaglandin found in various human malignancies, including colon, lung, breast, and head and neck cancer, also often associated with a poor prognosis.  In contrast, the enzyme that catalyzes the degradation of PGE2 (15-PGDH, an antagonist /suppressor of COX-2) is highly expressed in normal tissues but is ubiquitously lacking in human colon, gastric, lung and breast cancer. Lack of 15-PGDH expression in these tumours results in increased endogenous PGE2 levels. Furthermore there may be a negative feedback loop, since a product of the COX-2 enzymatic pathway, upregulates the expression of 15-PGDH in breast cancer MDA-MD-231 cells. 15-PGDH is being investigated as a potential avenue for tissue regeneration. PubMed.  Prostaglandin E Synthase (PGES) converts PGH to PGE. 
COX-1 inhibits PGE2 synthesis
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Brain ;
Joints;
 via Cox-2
flame

Inflammation /Pain

 brain
Promotes all signs of classic inflammation: i.e. redness, swelling and pain. Redness and edema result from increased blood flow into the inflamed tissue through PGE2-mediated increase in arterial dilation and microvascular permeability. Pain results from the action of PGE2 on peripheral sensory neurons and on central sites within the spinal cord and the brain
 Quercetin reduces PGE2 (RA joints Link)
Airways Constricted  airway

Bronchodilating

Vascular SMCs (in arteries, veins, lymphatic vessels);
SMCs are also in walls of stomach, intestine and bladder, and other hollow organs;

vasodilation effects

Vasodilating

 
Dilates smooth muscles cells (SMCs), which form the supporting tissue of blood vessels and hollow internal organs (e.g. stomach, intestine, and bladder)
normal_bp

Normalize BP

Platelets    
Gastric mucosa
via Cox1
gastric mucosal layer Protects stomach lining;
🠡 mucous /bicarbonate secretion;
🠡 mucosa blood flow;
🠣 gastric acid /PEPSIN secretion;
Provides gastrointestinal integrity (Cox-2?)
🠡 duodenal mucus secretion
Kidneys    
    Involved in fertility
    Regulates immune responses; 
     
 
PGF2α
 (Derived via Cox1, Cox2 from omega-6 AA  (in the Western diet, this is mostly from meat (especially chicken) and eggs); inhibited by omega-3 EPA presence;
Released area Action Information
Airways Constricted  airway

Bronchoconstricting

Anomaly: Promoted by Cox1 inhibitors (aspirin, traditional NSAIDs) Harrington, 2008
Vascular Smooth Muscle Cells (VSMCs) via Cox2 vasoconstriction

Vasoconstricting


high blood pressure

Raise BP

 
Uterus;
Bladder

Contraction

 
Eyes    
 
PGI2 (Prostacyclin)
(Derived from AA via Cox1, Cox2)
Released area Action Information
Endothelial
 cells lining inside of blood and lymphatic vessels
 (epithelial cells lining hollow
 organs, airways, gastrointestinal lining, skin)
via Cox-1 and
Cox-2
vasodilation effects

Vasodilating

 
PGI2 has a beneficial effect on allergic airway responses and pulmonary hypertension. e.g. in asthma. Zhou, 2016
normal_bp

Normalize BP

Airways Constricted  airway

Bronchodilating

 
Platelets
via Cox1 and
Cox2)
PGI2 Inhibits clot formation  
Kidney    
Gastric mucosa via Cox1 Protects stomach lining  
 
TXA2 Thromboxane
(TXA2-->TXB2) (from AA e.g. meat, eggs, or indirectly from LA in seed oils)
Released area Action Information

Vascular Smooth Muscle Cells (VSMCs) via Cox2
vasoconstriction

Vasoconstricting

 
 
high blood pressure

Raise BP

 

VSMC proliferation

Cell proliferation aids damage repair.
Involved in development of atherosclerosis;
Platelets;
via Cox1

Blood clotting

Involved in thrombosis
Airways Constricted  airway

Bronchoconstricting

An anomaly is that bronchoconstriction is promoted by Cox-1 inhibitors (aspirin, traditional NSAIDs), but not selective Cox-2 inhibitors Harrington, 2008
Placenta  
KIdney    
Macrophages    
 
Series 3 PGs
Derived from  omega-3 EPA  e.g. in salmon,
salmon, fish,
cod liver or
 krill oil
salmon on plate  Fish oil capsules
Fish oil capsules by Semtrio
 Licensed CC BY 2.0
Released area Action Information
Most cells
via Cox1 and
Cox 2
ice cube

Counters inflammation

COUNTER  PG-2s,  LT-4s
Compete for COX and LOX enzymes
Leukotrienes
Series 4 LTs
Derived from AA e.g. meat, eggs, or indirectly from LA in seed oils
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Mast cells
(concurrent
release with
histamine)
via 5-LO
Constricted  airway

Bronchoconstricting

Part of the inflammation response, especially in asthma and allergic rhinitis. Attract white blood cells to sites of tissue damage and cause smooth muscles to contract.
 
Series 5 LTs
Derived from omega-3 EPA e.g. in fish oil
Released area Action Information
Mast cells
via  5-LO
ice cube

Counters inflammation

 
 
Specialized pro-resolving mediators (SPMs
Deal with  reducing excessive tissue injury and resolving inflammation. 
Lipoxins
Released area Action Information
Low dose aspirin can trigger lipoxin synthesis
Platelets
via 12-LO
F
rom LTA5
   
Neutrophils
via 15-LO
From AA
 
Erythrocytes,
Reticulocytes
via 12-LO
From AA
   
Resolvins (RVs)
(from EPA, DHA, DPA e.g. fish oil)
Released area Action Information
  Newly discovered resolvins are anti-inflammatory and inflammation resolving. Clear away inflammation debris
Block prostanoid effects
Protectins (PDs)
from O3
Released area Action Information
       
Eoxins 
Eoxins (EX)
(from AA e.g. meat, eggs, or indirectly from LA in seed oils)
Released area Action Information
 Eosinophils
 (white blood cells), mast cells
via LOX
  Involved in asthma,  lymphoma of Hodgkins disease, prostate cancer, colon cancer, and other cancers

 

References

Garza, Luis A.; et al. (2012, Mar 12).  "Prostaglandin D Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia". Science Translational Medicine. 4 (126): 126ra34. PubMed

Green, P., Gispan-Herman, I., & Yadid, G. (2005). Increased arachidonic acid concentration in the brain of Flinders Sensitive Line rats, an animal model of depression. Journal of lipid research, 46(6), 1093-1096. PubMed


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Pulsed Electromagnetic Field Therapy (PEMFT)

   Electrotherapy

       "The medical kit of the future"

The Body Electric

General electrotherapy health benefits.   Used systemically and/or locally at specific problem areas of the body, its effective application has many benefits:

Detoxification Wellness / Healthy aging Pain relief 
Relief from insomnia Immune system restoral Anti-Inflammatory
Maximizes cellular energy production Accelerated tissue /bone
/scar healing
Stress Reduction
Muscle relaxation / rehabilitation Increased blood oxygen
/ circulation
+++

There are several reasonably affordable electrotherapy devices available for personal use. The following electrotherapies are those that have received a significant amount of positive feedback:

Cranial Electrotherapy Stimulation (CES) applies specific frequency patterns to the head area, with the following benefits:

Balances neurotransmitters Relieves pain Treats depression
Substance abuse withdrawal Relieves insomnia Relieve stress / anxiety
Anti-Inflammatory Fibromyalgia +++