TREATMENT OF INTERSTITIAL CYSTITIS WITH CHINESE MEDICINE

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

Interstitial cystitis (IC) appears to be a relatively new disorder. First reports of IC emerged during the early 20^th century, but it did not become a subject of medical investigation until the number of cases markedly increased during the 1970s. IC is almost exclusively a disorder suffered by women, who are estimated to make up 90% or more of the total cases. The number of people affected by IC is unknown; it has been suggested that most cases still go undiagnosed, but there are about 100,000 diagnosed cases at any given time (precise statistics are not available), and it has been claimed that this may be only 20% of the actual cases. The median age of symptom onset is 40, with only 25% of patients under the age of 30, most of those in their late 20s.

The nature of IC is not fully known. It is diagnosed tentatively by certain characteristic findings and by elimination of other disorders-mainly bacterial infections-from the list of possible alternative diagnostic categories (see Table 1). IC is suggested by reports of urinary bladder symptoms such as urinary urgency, frequency, and bladder pain, all of which can be caused by bladder infections, but urine tests show no evidence of infection or other obvious pathology, and antibiotics fail to resolve the symptoms. Further investigation by cytoscope (device for viewing the inside of the bladder, Figure 1) show only pinpoint submucosal hemorrhages (glomerulations) that become evident after distention of the bladder; there may be reduced bladder capacity, and there may be some ulceration (at one point, the disorder was distinguished as ulcerative or non-ulcerative IC, but this distinction is not deemed important). Pain symptoms are reported to worsen during menstruation. For most IC sufferers, the disorder may begin as an ordinary bladder infection, but it fails to resolve fully even after the usually-successful treatments for infections, and can progress in severity, so that the symptoms are extreme and debilitating (1,2).

Table 1. Diagnostics for Interstitial Cystitis

Figure 1: Cytoscope.

Practitioners of Chinese medicine who receive patient reports of characteristic symptoms, triggers of exacerbation, and accompanying syndromes, should refer the patient to a urologist for confirming diagnosis by manual and cytoscope exams as well as blood tests (see Table 1). A particular characteristic of this disorder is pain that occurs as the bladder begins to fill, with significant alleviation on voiding; as a result of this pattern, IC suffers may void dozens of times in one day.

A possible scenario for cause of IC is an autoimmune response that develops in susceptible individuals as a result of an earlier infection, perhaps by bacterial strains that have become more prevalent in recent decades. With this proposal, one imagines endothelial bladder cells-with altered membranes making them appear to the immune system as cells to be eliminated-are attacked, resulting in inflammation with degradation of the bladder mucosa. Alternatively, IC may be one localized manifestation of a systemic autoimmune disorder, one that started elsewhere in the body and which causes other pain syndromes. This scenario could apply, since many people with IC also suffer multiple pain syndromes, including other equally mysterious conditions, such as fibromyalgia or vulvadynia. The experience of flare-ups and remissions of the disorder that is often reported is consistent with experience of many autoimmune disorders. However, in only some cases are mast cells, characteristic of autoimmune processes, found in the urine of people with IC, leaving the mechanism of the disease obscure.

IC research has been hampered by the difficulty in defining the syndrome more precisely and by the difficulty of getting sufficient numbers of cases at one site where studies could then be conducted. Certain therapies are available, but it is difficult for urologists to offer a prognosis for their patients due to lack of sufficient data on responses. Instead, different approaches are tried to see if one appears to work. A therapy that has been in use for IC for 25 years is dimethyl sulfoxide (DMSO), an anti-inflammatory agent, that is instilled directly into the bladder. The first oral drug approved by the FDA (in 1996) for IC is pentosan polysulfate sodium (tradename: Elmiron). Its effects are limited; clinical trials showed a success rate in alleviating symptoms at 38%, and the duration of therapy until some symptom relief is noted may be as long as 2-4 months, while decrease of urinary frequency may require up to six months of therapy. Though its mechanism of action is unknown, it is thought that it slowly repairs the bladder mucosa. The drug has a low incidence of adverse effects, but it can rarely cause liver damage and has been known to cause reversible hair loss in some users.

Due to their limited satisfactory treatment options, patients with IC often seek out alternative therapies to find relief from their syndrome and hope for a possible cure. Practitioners of Chinese medicine, confronted with this disorder will find that most Chinese texts refer only to syndromes corresponding to infections, passing of stones, and obstruction of urination (uroschesis). For example, most of the textbook descriptions involve discharge of blood with the urine, which is not characteristic of IC. Medical reports from China do not include IC as a specific target of treatment. Until recently, China has lacked the equipment, such as cytoscope, to make a diagnosis, and it remains unclear whether this disorder is at all common in China. This article briefly explores potential Chinese herbal therapies and acupuncture for IC.

BASIS FOR SELECTING HERB THERAPIES

While Chinese medicine has a long history of application to numerous diseases, during recent decades, it has been applied to conditions never before experienced in its history. As examples, Chinese medicine has been applied to treating the side effects of modern cancer therapies, treating new diseases such as hepatitis C and HIV infection, and treating diseases that rarely occur in China, such as multiple sclerosis. The method for selecting herb therapies for conditions and diseases that are new or rare is to examine earlier therapies for diseases that have similar presentations, and to take into consideration modern diagnostic data in order to focus on certain therapeutic principles.

In the case of IC, the symptoms of urinary urgency, urinary frequency, and bladder pain are not different from those of some other bladder disorders, such as urinary tract infections. Therefore, herbal formulas that have been successful for bladder infections are tried for IC. Unlike antibiotic therapies, which are known to have no impact on IC, the Chinese herb therapies may have therapeutic functions that differ from merely inhibiting the bacterial activity. Most of the herbs utilized for the bladder syndromes are aimed at alleviating a condition defined as "damp heat of the lower burner (jiao)." These herbs have the properties of clearing heat and draining or drying dampness. The herbs are selected for having a primary action on the genito-urinary system. The source of the damp heat may be local (as occurs when there are bacteria introduced into the bladder through the urethra) or secondary to heat of the heart (usually indicated by emotional distress) or small intestine (often suggested by abdominal distress after eating).

The severity of pain, and its persistence, in IC indicates to Chinese doctors that a blood stasis syndrome is involved. Herbs that vitalize blood are frequently employed for lower abdominal pain syndromes and have been utilized for conditions such as uterine fibroids, endometriosis, and other causes of persisting abdominal pain. The herbs have the properties of invigorating circulation of blood and breaking down static blood.

The cytoscopic finding of hemorrhagic spots is consistent with a Chinese syndrome of blood stasis. Hemorrhage is sometimes considered to be a sequel to blood stasis, following the concept that the blood must "move around" the static blood and may, thereby, escape the vessels. Hemorrhage is also considered a secondary effect of a heat syndrome, especially heat in the blood, but since the hemorrhagic spots are apparently due to distention and not spontaneously occurring, and since they do not lead to actual discharge of any significant amount of blood, this sign is not necessarily to be associated with heat. In fact, many patients with IC report experiencing a dominance of cold-type symptoms aside from the bladder problem itself. The finding of hemorrhagic spots may lead to incorporating into a formula one or more herbs that restrain bleeding, especially herbs that have a dual function of vitalizing blood and restraining bleeding (e.g., san-chi and typha).

One cannot know if such considerations will result in successful therapy, but they can be a basis for applying traditional Chinese medicine principles and experience to the treatment of the new disorder. Informal reports of use of Chinese herbs to treat IC have been relayed by practitioners in America from time to time, and the formulas utilized tend to follow the therapies recommended in China for urinary tract infections.

HERBS OF POTENTIAL VALUE

Chinese herb books that make reference to treatment of urinary bladder syndromes usually give special attention to a traditional formula of the Taiping Huimin Hejiju Fang (ca. 1100 A.D.): Bazheng San (Eight Herb Rectifying Powder). This formula treats painful urination due to damp heat of the lower burner. Unlike IC, the disorder that it was designed to treat involves other signs of heat syndromes, such as dark, turbid, and scanty urine, and accompanying heat signs, such as rapid pulse and yellow tongue coating, and other damp signs, such as slippery pulse and greasy tongue coating. Still, these differences are instructive, in that they help point to the more localized nature of IC, without the requirement of finding systemic heat and damp symptoms. When produced as a powder, equal proportions of the eight ingredients may be used:

Bazheng San
Plantago seed (cheqianzi)
Dianthus (qumai)
Polygonum (bianxu)
Akebia (mutong)
Talc (huashi)
Gardenia (zhizi)
Rhubarb (dahuang)
Licorice (gancao)

The 8-herb powder is taken in doses of 6-9 grams each time, or it can be decocted first in somewhat higher dose and consumed as a drink. It is traditionally taken with 1.5-3.0 grams of juncus (dengxincao). A few other herbs are included in similar formulations or sometimes simply added to this one, primarily pyrrosia (shiwei) and abutilon (dongkuizi); these herbs are particularly used when there are urinary stones, but not exclusively for that purpose. In some of the ancient formulas, mirabilitum (mangxiao) or pharbitis (qianniuzi) are used in place of rhubarb, where all serve a role of promoting a laxative effect to clear stagnation, accumulation, and heat in the lower warmer. Rhubarb can be fried with a little wheat flour to reduce its purgative effect while retaining its ability to vitalize blood circulation and clear damp heat. In Western practice of Chinese herbal medicine, special cautions have been raised about using akebia (mutong), to avoid the commonly used species Aristolochia manshuriensis, and rely, instead of Akebia trifoliata, Akebia quinata, or Clematis armandi.

For abdominal pain due to blood stasis, commonly used herbs include: pteropus (weilingzhi) with typha (puhuang), myrrh (moyao) with frankincense (ruxiang), and corydalis (yanhusuo). A therapy widely used for endometriosis includes succinum (amber; hupo) with rhubarb as a treatment for persistent abdominal pain (turtle shell is included in the formulations to resolve the endometrial cysts, which is not a concern with IC).

In proposing any formulation for IC, reference to commonly used treatments is helpful, and herbs may be included or excluded based on their applicability to the specific presentation of IC compared to the disorders treated by the other herbs. The base remedy might be Bazheng San plus herbs for blood stasis, as mentioned above. Gardenia might be removed if there is no systemic heat syndrome (and knowing that there is no bladder infection); akebia might be replaced by pyrrosia and abutilon to avoid concerns about undesired herb substitution. A sample formulation would be:

IC Formula
Plantago seed (cheqianzi)
Dianthus (qumai)
Polygonum (bianxu)
Pyrrosia (shiwei)
Abutilon (dongkuizi)
Talc (huashi)
Rhubarb (dahuang)
Licorice (gancao)
Juncus (dengxincao)
Pteropus (weilingzhi)
Typha (puhuang)
Myrrh (moyao)
Frankincense (ruxiang)
Corydalis (yanhusuo)

These herbs could be provided in the form of decoction or dried decoction, with san-chi (sanqi; tien-chi ginseng) powder and succinum powder provided separately (these herbs are usually not decocted, and are instead given as powder or tableted powder). In total, there are 14 herbs in the decoction plus two herb powders, and the size of this formulation is not unlike those often given to patients with chronic diseases. The aim of the formula is to reduce inflammation, open the natural flow of urine, reduce pain, and aid healing. Its nature is very bitter and slightly cold (the cold herbs are plantago seed, dianthus, abutilon, talc, rhubarb, and juncus; polygonum, pyrrosia, licorice, myrrh, and typha are neutral; pteropus, frankincense, and corydalis are warm).

A formula that has been presented for use in treating IC in the U.S. was developed by Ching-yao Shi about 10 years ago, based on combining gardenia and rhubarb of Bazhen San with kidney tonic herbs: rehmannia, dioscorea, hoelen, and cornus of Liuwei Dihuang Wan (Rehmannia Six Formula) and curculigo, morinda, and anemarrhena of Erxian Tang (Two Immortals Decoction). The tea formulation is:

Gardenia (zhizi)
Rhubarb (dahuang)
Rehmannia (shudi)
Dioscorea (shanyao)
Hoelen (fuling)
Cornus (shanzhuyu)
Cuscuta (tusizi)
Curculigo (xianmao)
Morinda (bajitian)
Anemarrhena (zhimu)

Her theoretical basis for the formulation, which is claimed to provide relief to many patients (significant improvement to just over half of them in an uncontrolled evaluation), is that IC occurs when the kidney qi is weak, hence the emphasis on kidney tonification therapy. The herbs gardenia, rehmannia, and cornus have iridoid glycosides as major active components; these have been shown to produce anti-inflammatory effects.

ACUPUNCTURE THERAPY

Perhaps to a greater extent than with herbs, acupuncture therapy is not specific to the disease being treated but is suited to treating the manifestations, which may be similar for different diseases. Acupuncture is especially effective for prompt alleviation of acute symptoms of the disease.

Training in acupuncture therapy includes learning of certain points that can treat pain in the lower abdomen, as well as selection of meridians for therapy aimed at alleviating bladder disorders. Among the commonly recommended points are those on the urinary bladder channel and the governing (du; GV) and conception (ren; CV) channels, with emphasis on local points (those in the region of the bladder). Examples are CV-3 (zhongji), CV-4 (guanyuan), and CV-6 (qihai); GV-4 (mingmen); and BL points (running from BL-22 to BL-35 on the inner channel, and BL-51 to BL-54 on the outer channel). Distal points are utilized to regulate overall circulation of qi and blood to affect the bladder region; in particular, SP-9 (yinlingquan) is needled to promote free urination.

In a study of acupuncture and moxibustion for female urethral syndrome (3), the authors indicated that the basis of the disease being treated was persistent urinary tract infection that was resistant to treatment by antibiotics. The symptoms included frequent urination, urgency, dysuria, abdominal distention and bearing-down pain. Cytoscopy did not reveal evident lesions. The condition is consistent with IC, but the patient group may also have included those with what is commonly called "overactive bladder" or "irritable bladder." The authors selected two groups of points:

For patients with damp heat syndrome, SP-9 (yinlinguqan) and KI-8 (jiaoxin) could be added to either group. The points CV-6 and GV-4 were treated by acupuncture and moxibustion, the other points were treated by acupuncture only, using the tonification procedure for manipulating the needles at all points. For each treatment, points from one group would be selected, and then the other group, alternating point groups from one treatment to the next. Only 3-4 points would be treated each day, selected from the above groups. Long needles were used to treat BL-35 and BL-29 to get a needling sensation that would radiate to the lower abdomen and perineum. Moxibustion was performed by burning three cones on a medicinal herb cake through which the acupuncture needle was first inserted to reach the acupoint.

Acupuncture was administered every other day, with ten treatments making a course of therapy, and patients were treated for one to two courses (hence, about 1-2 months total duration of treatment based on three treatments per week). The authors of the study claimed that for a group of 128 patients treated by acupuncture, just over 50% of the patients had remarkable improvement in the characteristic symptoms. On average, the frequency of urination (both day time and night time) was reduced by about half in the acupuncture group. A control group of 52 patients, who did not receive acupuncture, but did receive a low dose of an herbal patent medicine formula in tablets, displayed only minor improvements that were neither statistically or clinically significant.

As part of the study, the researchers evaluated the urination flow rate, intrabladder pressure, and urethral pressure. They determined, based on the observations and measurements, that high urethral pressure was a feature of the disorder being treated in most of the women. The authors described their understanding of the syndrome and the effect of acupuncture:

The cause of elevation of the urethreal pressure is not yet clear. Some specialists consider that elevation of the urethral pressure in patients with urethral syndrome may be related to the increase of excitability of pudendal nerves innervating the urethra and sympathetic nerves. This excitability of nerves induces spasm of the external sphincter of the urethra, the smooth muscle of the bladder neck, and pelvic floor muscles (also innervated by pudendal nerves), resulting in elevation of uretrhal pressure, increase of urethral resistance and disorder in urination. Based on the previous studies, it can be seen that the nerves under the acupoints chosen in this study all enter the spinal segments of L1 to L5, corresponding to nerves innervating the urethra. Hence, when stimulating these points by acupuncture and moxibustion, especially deep puncture of huiyang (BL-35) and zhonglushu (BL-29), the tip of the needle can reach directly the nerves nearby in the pelvic cavity, resulting in afferent impulses spreading to the urination center to inhibit related neurons excessively excited, relax the urethral sphincter and pelvic floor muscles, and lower the urethral resistance.

In essence, the symptoms are alleviated because pressure in the bladder and urethra is reduced by an action of the acupuncture needles on blocking excessive nerve impulses. This specific mechanism may or may not be entirely relevant to IC. However, if the acupuncture treatment can adjust the nerve impulses to the bladder, it may be possible to alleviate some of the sense of urgency that occurs with small amounts of urine in the bladder and it may also reduce some of the inflammatory processes that occur in the bladder lining.

The two points of specific concern, BL-35 and BL-29, had been used previously by the authors to treat urinary disturbances that were complications of diabetes. These two points were also the focus of a recent article on their physiology, with examples of clinical applications of treating urethral syndrome, prostate pain, and sciatica (4). The author, Chen Yuelai, states (text edited slightly for clarity):

Both huiyang and zhonglushu are acupoints of the bladder meridian of foot-taiyang located in the sacral region. These two points are often used in combination to treat urinary dysfunction, and their regulatory effects are very satisfactory. Huiyang can be detected at 0.5 cun lateral to the coccyx, which is the crossing spot of the bladder meridian and the du meridian [governing vessel]. It functions to warm yang, promote diuresis, and improve the micturating function of the urinary bladder. Zhonglushu is 1.5 cun lateral to the du meridian at the level of the third posterior sacral foramen. It is used for regulating the lower jiao, strengthening the waist and kidney, and regulating the flow of qi to promote diuresis.

Their stratified anatomy is: skin, subcutaneous tissue, greatest gluteal muscle [gluteus maximus]. The nerves distributed from shallow to deep in these point areas are the middle clunial nerve, inferior gluteal nerve, pelvic nerve, and branches of the pudendal nerve. Among them, the pelvic nerve plexus is distributed in the pelvic organs, such as the urinary bladder, urethra, prostate gland, womb, vagina, and rectum. During excitement or inhibition, the nerves will release corresponding transmitters and induce either contraction or relaxation of the smooth muscles of these organs. If there is a disturbance in contraction or relaxation due to diseases of the nerve itself or due to the impact of other factors, the functional disorders of the organs involved may occur. When there is functional disturbance of the nerves that control the smooth muscles of the urethra and urinary bladder, the functional disturbance of the sphincter muscle of the urethra and detrusor urinae [the muscle whose function is to expel the urine] may occur, resulting in frequent or urgent micturition, enuresis, and dysuria.

The author then gives a case example of urethral syndrome that seems consistent with IC, though it may simply present similar symptoms. The woman, aged 38, had suffered from urinary urgency and frequent micturition for three years. This had started with a urinary tract infection that had improved after treatment of antibiotics, but then the symptoms returned and became more severe and persisted. The patient was treated with acupuncture, using huiyang and zhonglushu as main points along with BL-32 (ciliao), BL-33 (zhongliao), and BL-40 (weizhong). The needling method and its results were described as follows:

In needling huiyang, oblique insertion of 3-4 cun was performed with the needle tip pointed toward the pubic symphysis, and in needling zhonglushu, oblique insertion of about 3 cun alongside the margin of the sacral bone was performed. The needling sensations were made to transit to the lower abdomen. Repeated lifting and thrusting were carried out to strengthen the needling sensation. After the arrival of qi, the manipulation of reinforcement was performed by twirling the needles. For the rest of the points, the needling depth was about 1.5 cun and the manipulation of reinforcement was also performed, with the needles retained for 20-30 minutes. The treatment was given once every other day and ten treatment sessions made up one therapeutic course. After two courses, the patients felt that her urgent and frequent micturition was remarkably improved and other symptoms were relieved greatly....Then, five more treatment sessions were given before all of the symptoms disappeared. A follow-up two months later found no relapse at all.

Thus, a course of 25 treatments was used (during a period of about two months) to resolve this disorder. In a prior report, huiyang had been used as a single point for treatment of postpartum inhibited urination (5). This condition is due to prolonged compression of the perineal nerve by the head of the fetus. Since this nerve originates from the sacral nerve plexus under the huiyang point and innervates the urethra and sphincter of the bladder, needling of this point was usually able to restore normal urinary control. Such control over urination is not a significant focus for treating IC, as the problem of urgency and frequent micturition is likely the result of the irritation of the nerves within the bladder. However, the apparent ability of acupuncture therapy-at points affecting the nerves that enter the bladder and urethra-to resolve functional disorders suggests that this type of therapy may prove of benefit to sufferers of IC. Further, if the mechanism of action for acupuncture involves regulating the pelvic nerves that affect not only the bladder, but also the genitals, it is possible that these treatments will also alleviate accompanying symptoms of vulvadynia.

A therapy developed in 1981 called sacral nerve root stimulation has been evaluated for treatment of interstitial cystitis (6, 7), and has been applied as a treatment for other lower abdominal disorders, including regulating bowel function and alleviating vulvadynia and vulvar vestibulitis (8), with positive results. There is likely a similarity in the effects of treating huiyang and zhonglushu by acupuncture and by this particular nerve stimulation technique, giving further support to the concept that regulating the nerves by physical stimulus can alleviate the disease symptoms.

REFERENCES

1. Metts JF, Interstitial cystitis: urgency and frequency syndrome, 2001 American Family Physician, 64: 1199-206, 1212-1214.
2. National Kidney and Urologic Diseases Clearing House, Interstitial cystitis, 2002 NIH Publication Number 02-3220, Bethesda, MD (http://www.niddk.nih.gov/health/urolog/pubs/cystitis/cystitis.htm).
3. Zheng Huitian, et al., Study on acupuncture and moxibustion therapy for female urethral syndrome, Journal of Traditional Chinese Medicine 1998; 18(2): 122-127.
4. Chen Yuelai, The anatomical physiology and clinical application of the points huiyang and zhonglushu, Journal of Traditional Chinese Medicine 2002; 22(3): 180-182.
5. Li Ling, Zhoug Jifang, and Shi Xipeng, 103 cases of postpartum uroschesis treated by acupuncture at huiyang point, Journal of Traditional Chinese Medicine 1996; 16(3): 198-200.
6. Maher CF, et al., Percutaneous sacral nerve root neuromodulation for intractabale interstitial cystitis, Journal of Urology 2001; 165(3): 884-886.
7. Comiter CV, Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study, Journal of Urology 2003; 169(4): 1369-1373.
8. Pettit PD, Thompson JR, and Chen AH, Sacral neuromodulation: new applications in the treatment of female pelvic floor dysfunction, Current Opinions in Obstetrics and Gynecology 2002; 14(5): 521-525.

May 2003