Substance p /Stress in Intersitial cystitis and other conditions

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Treatment

 

There is no cure for IC, and there are no standard or consistently effective treatments. Results vary from person to person. As long as the cause is unknown, treatment is based on trial and error until you find relief.

 

Elmiron is the only medication taken by mouth that is specifically approved for treating IC. This medicine coats the bladder like Pepto-Bismol coats the stomach.

 

Other medicines may include:

 

Opioid painkillers for severe pain - extreeme caution in mast cell activation / mastocytosis

 

Tricyclic antidepressants such as Elavil (amitriptyline) to relieve pain and urinary frequency - NOT in Mast cell activation / Mastocytosis due to interaction with Epinpeherine which patients carry and may need in anaphylaxis associated with this condition.

 

Vistaril (hydroxyzine pamoate), an antihistamine that causes sedation, helps reduce urinary frequency - has good safety record in Mast cell as hydroxyzine is a h1 antihistamine .its is well tolerted . It cna cuase drowsiness but if this expereincecd it wears off in 2 weeks .Dosing is begun at night to mitiigate the drowsy side effects .In mast cell patients all meds should be ebgun before 5pm to aviod confussion between medicine effects and the 2am histamine high in the body which give mast cell patients night time waking with symptoms .

 

Other therapies include:

 

Bladder hydrodistention (over-filling the bladder with fluid while under general anesthesia)

 

Bladder training (using relaxation techniques to train the bladder to go only at specific times)

 

Instilled medications - medicines are placed directly into the bladder. Medicines that are given this way include

 

dimethyl sulfoxide (DMS)- Must not be given to patients with known or suspected mast cell activation syndrome - becuase it destabilises mast cells and cuases degraunualtion .In those with systemic conditions this will lead to systemic mast celldegranulation and anaphylaxis . On mast cell sites several patients report their anaphylaxis following DMSO as the illest they have ever been .

 

Heparin, - can have ethanol or other contaninats have cused anaphylaxis to heparin .this is especially relavant in mast cell were 50% of patients dont tolerate alochol-ethanol and will have anaphylaxis to even tiny amounts (author included)

Clorpactin, /Clorpactin® WCS-90 - dodecylbenzenesulfonic acid + hypochlorus acid - kills bacteria .Some mast cell patients don't tolerate any cholrine based products .questioning should include what household products they aviod.

Lidocaine -

doxorubicin -

bacillus Calmette-Guerin (BCG) vaccine.

 

Physical therapy and biofeedback (may help relieve pelvic floor muscle spasms)

 

Surgery, ranging from cystoscopic manipulation to bladder removal (cystectomy)

 

Diet modification

 

Some patients find that changes in their diet can help control symptoms. The idea is to avoid foods and beverages that can cause bladder irritation. Below are some of the foods that the Interstitial Cystitis Association says may cause bladder irritation. These are all high histamine foods as would be avoided by an educted mast cell patient . see triggers page and

 

Aged cheeses

 

Alcohol

 

Artificial sweeteners

 

Chocolate

 

Citrus juices

 

Coffee

 

Cranberry juice (Note: Although cranberry juice is often recommended for urinary tract infections, it can make IC symptoms worse.)

 

Fava and lima beans

 

Meats that are cured, processed, smoked, canned, aged, or that contain nitrites

 

Most fruits except blueberries, honeydew melon, and pears

 

Nuts except almonds, cashews, and pine nuts

 

Onions

 

Rye bread

 

Seasonings that contain MSG

 

Sour cream

 

Sourdough bread

 

Soy

 

Tea

 

Tofu

 

Tomatoes

 

Yogurt

 

Experts suggest that you do not stop eating all of these foods at one time. Instead, try eliminating one at a time to see if that helps relieve your symptoms. But if you have many mast cellsymptoms -see symptoms page -you will find inporvement in avioding high histamine foods .

 

 

ic mastcells

In I/c bladder mast cells are activated .This occurs through substance p being sent out of sensory nerve endings -stress causes this nerve activity .

 

Once the nerves relase substance p - it activates mast cells through the gcoupled recptors .this leads to degranualtion =histamine and prostoglandin relase.t the blood vessel walls contan recptors for substance p -This causes swelling and increased permability of the veins .

 

This allows white blood cells into the tissues which through relase of various interukins produce infammation .

 

This then stimaualtes the sensory nerves leading to more subastance p release .Histamine and prostoglands also act independnatly on the blood vessels - causing further permability and movemnt of white blood cells -lymphoctes -t killer ,tcyctoxic , thelper and t1 -infmaation causing cells .

 

4 positive feedback lops keep this cycle going

1) histamine sunbtance p to and from nerves

2) sunstance p from the site cuasing pain =substance p release from nerves .

3)mast cellcontents being mast cellactivators -prostoglandins - d2, leucotrines , il4 and il5

4)Tcell interukins and direct activtion by menbrance recptors -ox40, -activate mast cells =more histamine =more infammation = more substance p due to histamine recptor activation on nerves.

iI/C is avery painful condition for several reasons

 

Histamine

-causing nerve irritation

-muscle spasm

- bleeding

- swelling of bladder wall

-traveling to local nreve roots in spinal cord which have histamine recptors

Prostoglandins

- causing muscle spasm

- dilation of blood vessels

 

It is often misdiagnosed as a water infection due to presence of protien -white blood cells in the urine on dip testing and pain . This pain cna be at rest or during sex and can be confussed with endometriosis symptoms due to this.

 

But on microbiology, culture and sensitivity -it is sterile

 

It is more commonly seen in Lupus and with co existing IBS in woman .(  Marinkovic,etal 2010 ) Please see section on IBS and Mast cells .several classes of IBS have been found to have higher than normal mast cell levels .( Glover 2012 )

Symptoms

 Women are 10 times more likely to have IC than men.The condition generally occurs around age 30 to 40, although it has been reported in younger people.

 

Symptoms

 

Pain during intercourse

 

Pelvic pain

 

Urinary discomfort

 

Urinary frequency (up to 60 times a day in severe cases)

 

Urinary urgency

 

Can lead to detrusor instability/ failure in some patients

 

 

Signs and tests

 

Diagnosis is made by ruling out other causes. Tests include:

 

Bladder biopsy

 

Cystoscopy (endoscopy of bladder)

 

he condition generally occurs around age 30 to 40, although it has been reported in younger people.

 

Urine analysis

 

Urine culture

 

Urine cytology

 

Video urodynamic

Endometriososis.

intersitial cystitis is often mis diagnosed as endometriosos -so is there aconnection between these conditions ?

 

yes

 

In study into endometrial lesions in 1989 -  Kempuraj D et al found increased numbers of activated mast cells in endometriosis lesions positive for corticotropin-releasing hormone and urocortin.

 

CRH and urocortin as we know from about mast cells -Both activate mast cells are are the stress hormones produced in sensory nerves and in the brain in response to stress . This study concluded in resonse to the finding that more tryptase positive mast cells were present and 89% of mast cells were activated and stanied postive for CRH and urocortin.that It is probable that mast cellactivation by CRH and urocortin were responsible for such high levels of activation and so inflammation in endometriosos .Also that tryptase is likley resposible for the fibrosis seen with this condition ,which leads to painfull and difficult to trea adhesions .

 

With mast cells also haveing receptors for (o)estrogen this could explain the cyclical nature of inflammation associated with endoemtrial lesions .

 

 

August 2012 - I will research for studies on endometriosis and petiechie in mast cellactivation and for any information on how the endometrial cells migrate or are developed in the wrong place in the abdomen as this study answers many questions and offers treatment options but doesnt explain this first point that endometrial lesions bleed . Are they actually endometrium or as in i/c the bleeding is occuring due to the effects of mast cellcontents and this happens to be monthly due to the mast cells being activated by oestrogen ?

 

i had assumed once endometriosis in my pelvis was excluded that my pelvic pain was pure i/c .but maybe its more complex .