Cystalgia treatment

Non-pharmacological approaches to treating cystalgia include methods that patients can use to reduce the severity of symptoms of the disease, such as reducing stress and anxiety, physical exercise and physiotherapy, sex therapy and counseling, training the bladder, rehabilitation of the pelvic floor and changes in diet [Nickel, 2004]. [1]

Drug treatment

Drug treatment of cystalgia consists of oral agents and intravesical instillations. These are analgesics, antihistamines, antidepressants, prostaglandins, immunosuppressants, etc. In the case of hormonal disruptions, substitution therapy is used.

1. Antiallergic drugs

Antihistamines. Since mast cells and their mediators, such as histamine, are key participants in the inflammation and pathogenesis of cystalgia [Moldwin and Sant, 2002], it has been shown that therapy that blocks the action of histamine improves symptoms. These include H1-blockers of hydroxyzine hydrochloride [Moldwin and Sant, 2002],  [2]as well as H2-blockers, such as cimetidine, which have been shown to significantly reduce pain and nocturia in a limited study of patients with interstitial cystitis [Thilagarajah et al. 2001]. [3]

Cimetidine is an antidepressant, has central and peripheral activity. Apply 300 mg three times a day before meals or with meals. It can cause a feeling of fear, flatulence, diarrhea, muscle pain, increased liver enzymes, anemia, impotence. The drug is not prescribed for children under 14 years of age, pregnant, while breastfeeding, with serious violations of the liver and kidneys.

Montelukast leukotriene-D4 receptor antagonists. The presence of leukotriene receptors in the muscle cells of the detrusor [Bouchelouche et al. 2001a]  [4]and elevated levels of E4 leukotriene in urine in patients with cystalgia indicate the role of these pro-inflammatory mediators in interstitial cystitis. Bouchelouche and colleagues reported on their experience in 10 women with cystalgia [ouchelouche et al. 2001b],  [5]which were treated with the montelukast leukotrin antagonist. They found that after 1 month of treatment with montelukast, there was a statistically significant decrease in the frequency of urination within 24 hours, nocturia and pain, which persisted for 3 months of treatment. After 3 months, the 24-hour urination rate decreased from 17.4 to 12 urinations (p = 0.009), nocturia decreased from 4.5 to 2.8 p = 0.019), and the pain decreased from 46.8 to 19.6 mm visual analogue scale p = 0.006). No side effects were observed during treatment.

2. Bladder Protectors

Pentosan Polysulfate (Elmiron). Pentosan polysulfate acts by covering the mucous membrane of the bladder and restoring the normal function of the glycosaminoglycan layer (GAG) [Moldwin and Sant, 2002]. Parsons and colleagues conducted a double-blind, multicenter study in which patients with cystaligia receiving pentosan polysulfate showed a decrease in symptoms of interstitial cystitis [Parsons et al. 2002b]. [6]

Pentosan sodium polysulfate is a synthetic sulfate polysaccharide that eliminates a defect in the epithelium of the bladder mucosa. For treatment, a dose of 300-400 mg per day is effective. It is administered as subcutaneous and intravenous injections. May cause hematoma at the injection site, pain, possible skin reactions, nausea, vomiting, fever. The drug is not recommended after strokes, bleeding ulcers, cerebrospinal anesthesia, during pregnancy, because it can cause detachment of the placenta, miscarriage.

3. Pain modulators

Tricyclic antidepressants. Amitriptyline has been proven to be effective in treating chronic pain syndromes, including cystalgia [Hanno, 1994]. [7]Amitriptyline modulates the transmission of nociceptive stimuli by inhibiting presynaptic reuptake of serotonin and norepinephrine [Tura and Tura, 1990]. [8]Amitriptyline has been found to cause a 50% reduction in pain and urination [Hanno et al. 1989]. [9]Recently, in a randomized, double-blind, placebo-controlled clinical trial of amitriptyline in 44 women and 6 men with cystalgia that used a self-titration protocol (up to 100 mg / day at bedtime for 4 months), significant improvements in cystalgia symptoms were reported in all cases. [Van Ophoven et al. 2004]. [10]

Anticonvulsants Anticonvulsants, such as gabapentin, are often prescribed for neuropathic pain [Lukban et al. 2002]. [11]These drugs can be used to treat patients with refractory cystalgia who were not helped by other treatments [Butrick, 2003]. [12]

4. Hormone modulators

Leuprolide acetate. Many women of reproductive age with cystalgia often complain of worsening symptoms during the menstrual cycle [Powell-Boone et al. 2005]. [13]This may be due to the fact that estradiol activates estrogen receptors expressed on mast cells of the bladder, which, in turn, increases the secretion of the pro-inflammatory molecule [Spanos et al. 1996]. [14]In such cases, leuprolide acetate may be useful, as it is a gonadotropin releasing hormone agonist, causing a decrease in estradiol secretion. In 15 patients with irritable bladder symptoms and pelvic pain without endometriosis, symptoms decreased in eight out of nine patients receiving leuprolide acetate, and five out of six patients receiving oral contraceptives Lentz et al. 2002]. [15]

5. Anti-inflammatory drugs

Anti-TNF therapy. Recently, various studies have focused on the neuro-inflammatory mechanism of pain in order to further target specific pathogenetic links in therapy. A hypothetical model of a cholinergic anti-inflammatory pathway based on bacterial LPS as a stimulant is proposed, and treatment methods are being developed to specifically target and disrupt this neuro-inflammatory loop, such as anti-NGF to reduce SP or anti-TNF-α or neuromodulation, to break the loop and reduce symptoms [Saini et al. 2008]. [16]

Animal studies have shown that virus-induced neurogenic inflammation can lead to a 20-fold increase in degranulated mast cells in the lamina propria, which is primarily dependent on TNF-α [Chen et al. 2006]. [17] In addition, TNF-α can promote mast cell enlargement and cause inflammation of urothelium [Batler et al. 2002]. [18] These data served as the basis for the assumption of the possible use of anti-TNF therapy, although there are no clinical data for its use.

Anesthesia. Most patients with cystalgia experience chronic pain, although to varying degrees. The pain can be eliminated with opioids, either individually or in combination with hydroxyzine, to enhance the analgesic response and reduce side effects [Hupert et al. 1980]. [19]

Immunosuppressants. Immunosuppressants can be used as second-line therapy in the treatment of cystalgia. For example, prednisone can be used in treatment-resistant cases [Soucy and Gregoire, 2005]. [20] Other drugs, such as cyclosporine, have been shown to alleviate the symptoms of severe cystalgia [Sairanen et al. 2005]. In an open study in 11 patients with intractable cystalgia, treatment with cyclosporine for up to 6 months significantly reduced the frequency of urination and pain in the bladder in most patients [Forsell et al. 1996]. [21] Recently, in a randomized trial of 64 cystalgia patients who met the NIDDK criteria, patients received cyclosporin or pentosan polysulfate for 6 months. The clinical response rate was determined using the Global Response Score and was found to be 75% for cyclosporine compared to 19% for pentosan polysulfate (p <0.001) [Sairanen et al. 2005]. [22]

6. Bladder Protectors

Hyaluronic acid. It is believed that intravesical administration of hyaluronic acid protects the surface of the bladder. Morales and colleagues reported a positive symptom dynamics of 56% at week 4 and 71% at week 7 in 25 patients receiving intravesical instillation of hyaluronic acid [Morales et al. 1996]. [23] After 24 weeks, the effectiveness decreased.

7. Other drugs

L-arginine. In patients with cystalgia, there is a decrease in the level of nitric oxide synthase in the urine and the level of nitric oxide in the urine [Hosseini et al. 2004]. [24] These patients respond to treatment with oral L-arginine, a precursor to nitric oxide synthesis. In one double-blind, randomized, placebo-controlled study, 21 of 27 cystalgia patients received 1,500 mg of L-arginine over 3 months and compared with 25 of 26 placebo-treated patients: greater global improvement in L-arginine group (48%, 10 out of 21) compared with the placebo group (24%, 6 out of 25) after 3 months (p = 0.05) with a decrease in pain intensity (p = 0.04) [Korting et al. 1999]. [25] In another randomized, double-blind, cross-sectional study using 2.4 g of L-arginine in 16 patients with interstitial cystitis, the symptom score decreased by 2.2 for 1 month, but there was no significant difference in the frequency of urination or nocturia [Cartledge and others. 2000]. [26]

L-arginine is a solution for injection, administered dropwise intravenously at a rate of 10 drops per minute, after 10-15 minutes they accelerate the process to 30 drops. The daily dose is from 1.5 to 2.5 g for 3 months. Children can be used from 3 years. Contraindicated in people who are allergic to the components of the drug, severe impaired renal function. Adverse reactions are manifested by body aches, joint pain, nausea, vomiting, dizziness, and blood pressure spikes.

Anticholinergic drugs. Oxybutynin and tolterodine are commonly used anticholinergics to treat symptoms associated with an overactive bladder with interstitial cystitis. They both act mainly on the receptors of the muscarin-3 subtype (M3), which cause a reduction in bladder detrusor. Unfortunately, the salivary glands also have an M3 receptor, and therefore dry mouth is a major side effect, especially when using oxybutynin [Cannon and Chancellor, 2002]. [27] The US Food and Drug Administration (FDA) has approved a prolonged single daily tolterodine (Detrol LA). [Van Kerrebroeck et al. 2001] [28]

Dimethyl sulfoxide (DMSO). DMSO can have analgesic, anti-inflammatory, collagenolytic, muscle relaxant effects and is actually a standard treatment for cystalgia. In a controlled crossover study, 33 patients with interstitial cystitis were randomly divided into two groups: receiving 50% DMSO solution or placebo (saline). The drug was administered intravenously every 2 weeks for two sessions of four procedures each. The results were evaluated urodynamically and symptomatically. Subjective improvement was observed in 53% of patients receiving DMSO compared with 18% receiving placebo, and objective improvement in 93% and 35%, respectively [Perez-Marrero et al. 1988]. [29]

Bacillus Calmette - Guerin (BCG). BCG is most often used to treat recurrent or multifocal bladder cancer. A prospective, double-blind, placebo-controlled study in patients with cystalgia showed a 60% positive response in patients with BCG compared with 27% in patients receiving placebo [Peters et al. 1997]. [30] In another randomized, placebo-controlled, double-blind study in 260 patients with refractory cystalgia, BCG showed a 21% overall therapeutic response versus 12% for placebo (p = 0.062) [Mayer et al. 2005]. [31] Other multicenter studies are underway to determine the role of BCG in the treatment of patients with interstitial cystitis.

Other drugs, such as chondroitin sulfate, vanilloids, and intravesical botulinum toxin, may also be used alone or may be combined into a “drug shake” for intravesical instillation. Intravesical therapy is necessary for patients who do not respond to oral treatment or experience severe side effects from drug treatment (Forrest and Dell, 2007). [32] 

For the treatment of cystalgia, trioginal vaginal capsules are used. Estrogen estriol in its composition contributes to the restoration and renewal of the mucosa. The vaginal capsule is placed once a day, pre-wetted in a small amount of water. Local reactions are possible: irritation, itching, as well as tension in the mammary glands, an increase in vaginal discharge. It is not used for suspected cancer, endometriosis, thrombosis, jaundice, pregnancy, breastfeeding, hypersensitivity to the components of the drug, for children under 18 years of age.

Physiotherapeutic treatment

As part of a comprehensive treatment, they resort to manual therapy to strengthen the main one and as a supportive one. Several times a day, the area of projection onto the organ is massaged with light movements, which removes muscle tone.

Cystalgia is effective in gymnastics, soft tissue massage, including myofascial release and retraining of the bladder, are usually used in patients with little or no pain [Whitmore, 1994],  [33] which allows you to train the pelvic floor muscles. This is a wave of legs, twisting around the waist, palm rest, as for push-ups, a "bridge", exercises for the press. Intensive physical therapy should be used at the beginning of an exacerbation of the disease and should be repeated at least once a year.

There is also a special technique developed by the gynecologist Arnold Kegel. Having emptied the bladder, you need to tighten the muscles, stay in this state for a while, and relax. Repeat several times. Further strain and immediately release the pelvic muscles, accelerating. Ten approaches for each exercise for 5 times a day will give their results, reduce the symptoms of urinary incontinence.

A good result is obtained from the use of amplipulse therapy, acupuncture, reflexology,  [34] biological feedback to control pelvic floor dysfunction [35]

Alternative treatment

Of the alternative methods, decoctions and infusions of herbs, whose effect is soothing, are mainly used. For treatment, use mint, lemon balm, oregano. Pouring boiling water over raw materials and letting it brew for 20-30 minutes, drink 100 ml three times a day. In pharmacies, tinctures of valerian, hop, motherwort are sold, they are used according to the instructions. With inflammation fight half a floor, bearberry, knotweed, corn stigmas.

Homeopathy

Homeopathic remedies are also used to treat cystalgia, one of which is cystosan. Neuro-regulating, anti-inflammatory granules, which include beladonna, equise, clematis, chymafilla. In acute conditions, 3-5 granules are used 6 times a day, then 1-3 granules with a frequency of 2-3 times, taking breaks 1-2 days a week. There are no data on contraindications and side effects.

Homeopaths with this diagnosis prescribe Sepia (cuttlefish), the type of woman in this case is defined as a tired, thin, irritable during menopause.

For young, after childbirth or other genital injuries, Staphysagria (Stefan seed) is suitable. For pain over the bosom, Natrium muriaticum is prescribed, against the background of a gynecological disease - Platina.

Doses of drugs and the rules for their administration are determined by a homeopathic doctor.

Surgical treatment of cystalgia

Surgery is resorted to in severe cases that are not amenable to conservative therapy. Surgical treatment may include:

• sacral neuromodulation - acting on a neuron of the spinal cord, eliminate pain;
• transurethral resection - a cystoscope is inserted through a small puncture in the urethra, with which not only diagnostics, but also cauterization, removal of tumors are performed;
• laser fulguration - destruction of pathological foci with a laser; The study  [36]proved the effectiveness of laser therapy in the treatment of cystalgia. No intra- and postoperative side effects were found. In the treatment of cystalgia, the radiation of a helium-neon optical laser AFL-1 with a wavelength of 632.8 mm and an output power of 18-20 mW was used.
• cystectomy with the formation of an intestinal reservoir - removal of the bladder, resorted to in case of cancer;
• urine diversion.

Surgery is used as a last-line therapy when conservative options are ineffective.

• Bladder instillation

Although bladder distension can be used as a diagnostic procedure for cystalgia, it can also be used for therapeutic purposes (Moldwin and Sant, 2002). Most patients noted a worsening of symptoms within 2–3 weeks after hydrodistance, but then experienced a decrease in symptoms after this period of time. Glemain and colleagues tested the effectiveness of hydrodistance for symptomatic treatment of interstitial cystitis followed by follow-up after 6 and 12 months [Glemain et al. 2002]. [37] The treatment efficiency was 60% after 6 months, decreasing to 43.3% after 12 months. Erickson and his colleagues reported that the average symptom score in newly diagnosed patients decreases after hydrodistance, but only a small number of patients show a decrease in symptoms of at least 30% [Erickson et al. 2007]. [38]

A good result is exerted by instillations into the bladder of heparin and dimexide.

Dimexide - has an antiseptic, analgesic effect, is used in an aqueous 50% solution. The drug in a volume of 50 ml is administered 1-2 times a week for 4-8 courses. Contraindicated in atherosclerosis, cardiovascular failure, glaucoma, cataract, stroke, heart attack. May cause burning, itching.

• Transurethral resection of visible lesions

Transurethral resection (TUR) is intended only for patients with visible Hanner lesions. Fall reported on his experience with TUR in 30 patients with classic cystalgia and found that a complete TUR of all visible lesions led to the initial disappearance of pain in all and reduced the incidence in 21 patients [Fall, 1985]. [39] Although relapse was reported in one third of patients, the remaining two thirds still had no pain even after 2–20 months. In another study, Peeker and colleagues performed 259 TURs in 103 patients with cystalgia [Peeker et al. 2000a]; [40] In 92, improvement was observed, and in 40%, symptom relief lasted more than 3 years. 

• Laser coagulation

Transurethral ablation of bladder tissue is aimed at eliminating the visible ulcers of Hanner. Use of a neodymium laser: (Nd: YAG) has been proposed as an alternative to TUR for patients with cystalgia. Shanberg and colleagues initially treated five patients with refractory cystalgia with a neodymium laser, of which four had a cessation of pain and urinary frequency within a few days [Shanberg et al. 1985]. [41] Follow-up after 3-15 months did not reveal relapse, with the exception of mild recurrent symptoms of urination.

• Neuromodulation

Recently, unilateral stimulation of the sacral nerve (S3) has become a promising treatment option for cystalgia. Peters demonstrated that patients with interstitial cystitis, refractory to conventional therapy, responded well to stimulation of the sacral nerve [Peters, 2002]. [42] More recently, Comiter has confirmed the positive results of sacral neuromodulation during urination and pelvic pain in patients with cystalgia [Comiter, 2003]. [43]

• Cystectomy

When all conservative efforts fail, surgical removal of the bladder is the last and most extreme treatment option [Moldwin and Sant, 2002]. Three types of cystectomy for cystalgia can be performed: supratrigonal, subtrigonal cystectomy or radical cystectomy, including removal of the urethra. Van Ophoven and colleagues, for example, reported triangulation cystectomy and orthotopic replacement enteroplasty in 18 patients using ileocecal (n = 10) or iliac (n = 8) segments [Van Ofhoven et al. 2002]. [44] After 5 years, 14 (77.78%) patients did not experience pain, 15 (83.33%) reported complete resolution of dysuria.