Cannabinoids Treat Symptoms of Cystitis and Urethritis

Cystitis and Urethritis

 

Inflammation of the bladder and urethra, called cystitis and urethritis respectively, is usually caused by bacterial infection.  The bacteria involved are often normally harmless residents of the rectum, colon and vagina which for some reason invade the urinary tract and cause infection and inflammation.  Sometimes the cause can be traced to an abnormality of the urinary system, in which case surgery will often cure the problem.

Cystitis and urethritis are more common in women, usually during the sexually active years, because the shortness of the female urethra and its close relationship to the vagina makes it highly accessible to bacteria.  Urethritis can result if the urethra is bruised during sexual intercourse, when symptoms are caused by mechanical irritation rather than infection.  Because symptoms are so similar to those of cystitis and are common in women who have just started having intercourse, it is sometimes called 'honeymoon cystitis'.  Gynecological conditions such as infected erosion of the cervix may also cause urethritis by affecting the types of organisms found in the vagina. Contraceptives and some tampons have also been thought to cause cystitis and urethritis because they change the environment in the vagina, encouraging the growth of certain strains of bacteria that may then invade the urinary system.

Cystitis and urethritis in men most often occur as a result of either obstruction to the urethra by the prostate or an infection of the prostate spreading to the bladder and urethra.  Certain venereal diseases such as gonorrhoea, can cause urethritis in both sexes.  There may be a wide variety of other unidentifiable causes.

Symptoms

  • pain, discomfort, burning sensation
  • intense urge to urinate
  • unusually frequent urination
  • cloudy, foul odor, sometimes blood in urine
  • pain, pressure, tenderness in bladder area
  • In children:
  • crying during urination
  • bedwetting
  • pain in the side or mid back
  • fever, chills
  • nausea, vomiting

The symptoms of both conditions are similar: frequent passing of urine with intense, scalding pain.  There may be pain in the lower abdomen and a frequent, urgent, desire to pass  urine which, in the event, is only a small amount.

UTIs are generally quickly and easily treated with antibacterial drugs.  The choice of the antibiotic and treatment duration depends on the patient’s medical history and the results of the urine analysis identifying the invading bacteria.  Symptoms usually disappear within the first 24 to 48 hours.  It is very important to follow exactly the doctor’s prescription until the end of the treatment in order to limit the emergence of resistant bacterial strains.  If the prescribed antibiotic is not efficient after 48 hours, the doctor must be informed and he/she may prescribe a different antibiotic.  An immunostimulating bacterial extract can also be administered together with the antibiotic in order to boost the patient’s immune system.  This immunotherapeutic drug leads to decreased duration, severity and frequency of urinary tract infections, but not to the emergence of resistant  bacterial strains.

There are several simple measures which can be taken to reduce the risk of repeated attacks.  First is attention to hygiene - particularly in washing around the urethra, vagina and anus after defecating or  sexual intercourse.  Wearing loose-fitting, cotton underwear may also help, and nylon tights and tight jeans best avoided.  It is advisable to cut down on drinks (coffee) which tend to concentrate the urine and to drink plenty of water instead.  If bouts of cystitis appear to be linked with sexual intercourse  it may be worth using a lubricant  (KY  jelly)  to minimize possible bruising.

Urethritis:

Urethral infection.   Urinary tract infection.    Clinical studies have observed that in acute   cases there is an urgency to urinate with a severe burning sensation.  Some cases may have bloody urination.  However, most acute cases can be cured, although they may become protracted and recurrent when the body's resistance is low.  These infections are caused by bacteria.  Traditional Chinese Medicine includes them in the category of  "Lin (stranguria) Syndrome",  which is caused by damp-heat  flowing downward into the urinary bladder.  Inflammation of the urethra (transport tube leading from the bladder to discharge urine outside the body).   Urethritis can be due to several causes, including sexually transmitted diseases such as Chlamydia, or irritation.  Treatment depends on the cause.

Cystitis:

Inflammation of the bladder .  Cystitis can be due for example to infection from bacteria that ascend the urethra (the canal from the outside) to the bladder.  Symptoms include a frequent need to urinate, often accompanied by a burning sensation.  As cystitis progresses, blood may be observed in the urine and the patient may suffer cramps after urination.  In young children, attempts to avoid the pain of cystitis can be a cause for daytime wetting (enuresis).  Treatment includes avoiding irritants, such as perfumed soaps, near the urethral opening;   increased fluid intake; and antibiotics.  Untreated cystitis can lead to scarring and the formation of stones when urine is retained for long periods of time to avoid painful urination.

Pyelonephritis:

is a serious infection of the urinary tract.  It is located in the kidneys, after the bacteria have migrated from the bladder through the ureters up to the kidneys.

Treatments

Isolation and identification of the bacteria causing the infection are an important part of the diagnosis, and analysis of a urine sample obtained under sterile conditions is essential.  Antibiotics effective against the specific organism identified as the cause of the infection will cure it in most cases.  Unfortunately, some people, particularly women, have recurring infections which are resistant to treatment. UTIs are generally quickly and easily treated with antibacterial drugs.

 

Subjects at risk for UTI

Women, especially those sexually active.  The infection rate is 50% higher than in men. One factor explaining this difference may be that a woman’s urethra is short, allowing bacteria a quick access to the bladder.  A woman’s urethral opening is also near sources of bacteria from the anus and the vagina, facilitating bacterial contamination.
Pregnant women because of the pressure applied by the baby on the urinary system, but also because of the hormonal changes  linked to pregnancy.
In some women using a diaphragm for contraception, the urethra may be compressed, impairing the complete emptying of the bladder and thus favoring bladder infections.

Some women using spermicides as contraception may develop a urethritis.
Men with benign prostatic hyperplasia, as the enlarged prostate compresses the urethra, thus decreases the urine flow, preventing the complete emptying of the bladder and favoring germ proliferation.
Diabetics due to their high blood sugar level favoring bacterial growth and their increased susceptibility to infections following changes in the immune defence system.
Children and adults with a structural urinary tract abnormality or kidney stones that obstruct or impair the flow of urine.
Subjects with indwelling catheter or tube in the urethra and the bladder facilitating bacterial contamination

Home remedies:   use a teaspoon of drumstick flower juice and mix it with coconut water taken twice daily. To avoid using medication, you can also drink radish leaves juice once daily which would surely make you feel better.  Some feel it is best to treat infections with natural products, hence you can also try spinach juice mixed with coconut water. Drink twice daily. for your cystitis. Cranberry juice is excellent for clearing the bladder.
Urethritis and cystitis do not necessarily occur at the same time (together).  However, frequently the two coincide.  When they occur together it is called UTI (urinary tract infection).  Another treatment for cystitis is radiation cystitis treatment.  In radiation cystitis treatment, radiation helps in treating the infected area and prevents the infection from spreading in any other organ.  The flip side of this treatment is that the tissue near the infected area could get affected by the radiation beam.  This treatment is used when the infection becomes very severe.

Prevention and management of UTI

Several different approaches are available:

  • General preventive measures
  • Drink several glasses of water each day. Fluids hinder the growth of bacteria by flushing out the urinary tract. Drinking cranberry juice or taking vitamin C supplements may also curb bacterial growth.
  • Urinate when the need arises, don’t resist the urge to urinate.
  • Take showers instead of tub baths.

After having a bowel movement, wipe from front to back to prevent the spread of intestinal bacteria from the rectum to the urinary tract in women.
If possible, for women, cleanse the area around the genitals before having sex.  Urination after sexual intercourse helps to flush bacteria from the bladder.
Avoid using feminine hygiene sprays and scented douches which may irritate the urethra.

Pharmacological preventive measures

Immuno-stimulating bacterial extract: reinforces the body’s immune defenses,  thus contributing to decreasing  the frequency, duration and severity of urinary tract infections.  Such medication is devoid of the risk of developing bacterial resistance as is the case with several antibiotics, thus making them inefficient against bacterial infections.
There is presently no vaccine on the market for preventing UTIs, but research is under way.
In some patients with frequent UTIs (more than two infections every six months), antibiotics may be prescribed as prevention.  The antibiotic taken either daily at low dose for 6 months or longer, or at a single dose after sexual intercourse, or for one or two days when symptoms occur.

Urinary System Comfort

The urinary system does more than most people realize.  I t plays an essential part in metabolism and is not just a way of getting rid of excess water and waste material.  

Urethritis

Urethritis is an inflammation of the urethra, which is the tube through which urine passes out of the body. A bacterial infection is the most common cause in both men and women.  Symptoms and signs include:

  • burning sensation and occasionally pain on urinating,
  • blood in the urine, and
  • sometimes a yellow discharge.

What you can do to help

Take 1 gram of vitamin C daily as a natural diuretic and immune system boost.
Take a good multivitamin and mineral supplement.
Drink plenty of water to flush the system.

Eat live yogurt or acidophilus to balance the body's bacteria. It is particularly important to take these if you have had a course of antibiotics prescribed so that the natural healthy bacteria can be re-established in the bowel.
Drink cranberry juice daily to discourage bacteria from sticking to the wall of the urethra. It modifies the urinary pH which both treats and prevents the condition.

Garlic is able to act as a natural antibiotic and can assist in the treatment of the condition.
Following defecation take care not to take bacteria from the bowel region of the body and put them near the urinary region of the body. Bacteria that are harmless in the bowel region can cause infections in the urinary tract. Females are particularly at risk.  If the condition is left untreated it can develop into cystitis.

Cystitis

Cystitis is inflammation of the bladder.   Usually caused by a bacterial infection that enters the bladder  via the urethra.  More women than men suffer from this condition because the female urethra is shorter and closer to the bowel than it is for men.
The bowel is a site for many bacteria  (which cause no problems for the bowel ),   but can cause an infection,  if they are transferred to the urinary system.

The symptoms and signs of cystitis are:

  • constant urge to pass urine
  • painful, burning sensation when passing urine
  • fever
  • dull backache
  • cloudy or blood stained urine.
Cystitis is an inflammation of the bladder lining

and is often caused by bacterial infection.  Women are more prone than men because the female urethra is shorter and more vulnerable to infection.  Symptoms include urgency to urinate, and the frequent passing of small amounts of urine with a burning or stinging pain, and sometimes with blood.  Some people also feel feverish and ill.

Urethritis is a sexually transmitted disease

which may also cause inflammation of the whole urinary tract.  It can lead to pelvic inflammatory disease and sterility.  For urethritis and severe or  recurrent cystitis, it is advisable to consult your doctor.

Dietary Advice: Avoid Cystitis And Urethritis

Drink about 2 liters of water a day to dilute the urine.  Cranberry juice is one of the best natural remedies for cystitis as it prevents the growth of bacteria.  Drink 3 glasses a day, diluted with water or mixed with aloe vera juice.  Avoid alcohol, and replace tea and coffee with Chinese green tea, which is cooling and contains antioxidants to help the body fight infection.  Barley water, made by boiling 1 g of barley in 1 liter of water for 30 minutes, soothes symptoms when cooled, strained and sipped through the day.  Taking 400 to 500 mg vitamin C  twice a day while symptoms last may also speed recovery.

Natural Remedies  For Cystitis And Urethritis

Add 6 drops juniper berry or Scots pine essential oil to a large bowl of lukewarm water and sit in it for 15 minutes a day.  If pregnant, avoid juniper berry oil.
Nettle has a diuretic effect, helping to cleanse the body of toxins and waste.  Take the tincture in water, or make Nettle tea from the fresh or dried leaves.  Yarrow tea is also useful for cystitis.  Add 1 to 2 tsp of the dried herb to a cup of boiling water.  Drink 3 times a day.
The homeopathic remedy Cantharis  can help to clear painful, scalding cystitis when taken every half hour for up to 10 doses.  Staphysagria  can help with cystitis after sex.  Try Sarsaparilla if there is burning pain after urination.

Cystitis, vaginitis, urethritis & proctitis

These four infections are part of a group of infections called 'Non-specific genital infections' (NSGIs).
The four most common NSGIs are:

  • Vaginitis (inflammation of the vagina)
  • Urethritis (inflammation of the urethra)
  • Cystitis (inflammation of the bladder)
  • Proctitis (inflammation of the rectum)

NSGIs may be caused by chlamydia, particularly in men. Some of them, like cystitis, are not necessarily passed on by sexual contact.
How to recognise them:
Symptoms of NSGIs include :

  • Discharge from the vagina, urethra or anus
  • Inflammation around the genital area
  • Pain or a burning sensation when passing urine.

NSGIs can be treated with antibiotics.

What you can do to help
Take 1gram  of vitamin C daily as a natural diuretic and immune system boost.
Take a good multivitamin and mineral supplement.
Drink plenty of water to flush the system.
Eat live yogurt or acidophilus to balance the body's bacteria.  It is particularly important to take these if you have had a course of antibiotics prescribed so that the natural healthy bacteria can be re-established in the bowel.
Drink cranberry juice daily which will discourage bacteria from sticking to the wall of the bladder and urinary tract.  It both treats and prevents the condition.

Garlic is able to act as a natural antibiotic and can assist in the treatment of the condition.
Following  defecation take care not to take bacteria from the bowel region of the body and put them near the urinary region of the body.  Bacteria that are harmless in the bowel region can cause infections in the urinary tract.
If the condition is left untreated it can develop into an infection in the kidneys.  It is important to avoid this.

Herbal treatment for cystitis

The herbal approach to cystitis is essentially the same as for urethritis. Herbs like those below may be used:

  • bearberry,
  • buchu,
  • couchgrass,
  • juniper berries (do not use juniper berries if there is any tendency towards a tender or inflamed kidneys),
  • yarrow.

The following mixture will be most helpful:

    1 part bearberry
  • 1 part couchgrass
  • 1 part yarrow

Combine the ingredients.  Take 1 teaspoon of the herb blend and place into a suitable sized saucepan and pour over one cup of boiling water.  Allow this to stand for 10-15 minutes.  Strain out the herbs.  Drink a cup of this tea hot every two hours as long as the cystitus is acute, then three times per day for a while to totally cure it.

If the burning is very strong or if there is blood in the urine then an  herb to sooth the membranes, such as (corn silk)  can be added.  Other beneficial flora:

  • quack grass
  • plantain leaf
  • psyllium

Cannabinoids Treat Symptoms of Cystitis and Urethritis

The possibilities for cannabinoid medicines are very promising, and much exciting research is proceeding at a rapid pace.  As new FDA-approved cannabinoid products become available, physicians and patients will have a solid scientific foundation from which to assess their appropriateness.  Hopefully, robust scientific data will soon allow cannabinoids to take their place – along with opiates and other pain relievers – in the modern medical supply .

Research

Endogenous Cannabinoids and NGF Signaling in Pain Associated with Cystitis Abstract: Painful bladder
Painful bladder disorders are characterized by urinary frequency, urgency, and debilitating pelvic pain that affect more than 1.5 million people in the United States. Estimates of the annualized cost of treatment of patients with chronic pelvic pain range up to $3 billion. Visceral pain is the most debilitating symptom, and neurological mechanisms underlying visceral pain remain largely unknown. Currently available options for controlling bladder pain are not effective in all patients. Endogenous cannabinoids (endocannabinoids) function to limit inflammatory pain, but very little is known about their function in the bladder. We have found that inflammation of the bladder stimulates release of endocannabinoids, particularly anandamide (AEA). Previous research indicates that inflammatory mediators, particularly nerve growth factor (NGF), released from inflamed tissues play an important role in sensitization of afferent nerves and development of visceral pain. This research will employ unique methodology to measure release of endocannabinoids by the bladder in response to inflammation and the effects of inhibition of fatty acid amide hydrolase (FAAH, the enzyme primarily responsible for metabolism of AEA) on bladder pain.

We will further investigate the capacity of cannabinoids to inhibit sensitization of afferent dorsal root ganglia neurons by NGF using in vitro techniques, including patch clamp studies. We will also use mice that are deficient in FAAH or one of the primary cannabinoid receptors (CB1 or CB2) to test the novel hypothesis that endocannabinoids inhibit visceral pain arising from bladder inflammation and that this effect is mediated at least in part by inhibition of the effects of NGF. The long range goal is to provide improved options for treatment or prevention of bladder pain that have fewer undesirable side effects than those associate with currently-available therapeutic options. PUBLIC HEALTH RELEVANCE: Painful bladder disorders are characterized by urinary frequency, urgency, and debilitating pelvic pain that affects more than 1.5 million people in the United States at an annual cost of as much as $3 billion. The proposed research will investigate the potential for control of bladder pain by manipulation of endogenous cannabinoids produced by the body to inhibit pain by suppressing the effects of nerve growth factor (NGF), a known mediator of bladder pain.

Abstract: Painful bladder disorders are characterized by urinary frequency, urgency, and debilitating pelvic pain that affect more than 1.5 million people in the United States. Estimates of the annualized cost of treatment of patients with chronic pelvic pain range up to $3 billion. Visceral pain is the most debilitating symptom, and neurological mechanisms underlying visceral pain remain largely unknown. Currently available options for controlling bladder pain are not effective in all patients. Endogenous cannabinoids (endocannabinoids) function to limit inflammatory pain, but very little is known about their function in the bladder. We have found that inflammation of the bladder stimulates release of endocannabinoids, particularly anandamide (AEA). Previous research indicates that inflammatory mediators, particularly nerve growth factor (NGF), released from inflamed tissues play an important role in sensitization of afferent nerves and development of visceral pain. This research will employ unique methodology to measure release of endocannabinoids by the bladder in response to inflammation and the effects of inhibition of fatty acid amide hydrolase (FAAH, the enzyme primarily responsible for metabolism of AEA) on bladder pain. We will further investigate the capacity of cannabinoids to inhibit sensitization of afferent dorsal root ganglia neurons by NGF using in vitro techniques, including patch clamp studies. We will also use mice that are deficient in FAAH or one of the primary cannabinoid receptors (CB1 or CB2) to test the novel hypothesis that endocannabinoids inhibit visceral pain arising from bladder inflammation and that this effect is mediated at least in part by inhibition of the effects of NGF.

This study assessed the effects of two N-acylethanolamides in established rat models of visceral and somatic inflammatory pain. (1) The therapeutic effects of the cannabinoid anandamide and the putative CB2 agonist palmitoylethanolamide were tested in a model of persistent visceral pain (turpentine inflammation of the urinary bladder). Both anandamide (at a dose of 25 mg/kg) and palmitoylethanolamide (at doses of 10-30 mg/kg) were able to attenuate the viscero-visceral hyper-reflexia (VVH) induced by inflammation of the urinary bladder. (2) The effects of the same compounds on the behavioral response to subcutaneous formalin injection were assessed. The characteristic biphasic response was observed in control animals. Anandamide (dose range 5-25 mg/kg) and palmitoylethanolamide (dose range 5-10 mg/kg) both reduced the second phase of the response. The results confirm the analgesic potential of endogenous ligands at cannabinoid receptor sites. The anti-ciceptive effect of the putative CB2 receptor agonist, palmitoylethanolamide, is particularly interesting since it is believed to be a peripherally mediated effect. This observation might be exploited to separate central psychotropic effects from peripheral analgesic actions of the cannabinoids, under inflammatory conditions.

Sativex has a different delivery system – an oromucosal/sublingual spray absorbed by the lining of the mouth – that, according to the manufacturer, generally allows patients to gradually work up to a stable dose at which they obtain therapeutic pain relief without unwanted psychologic effects.

In the United States, Sativex is being studied in large randomized trials in cancer pain that has not been adequately relieved by opioids. Three early and six pivotal controlled studies in the United Kingdom demonstrated positive results treating chronic pain of various origins including neurologic pain, various symptoms of multiple sclerosis, rheumatoid arthritis, and cancer pain. Initial results show improvement in pain for more than one year despite lack of effectiveness of the opioids.

Additional research also may uncover other ways of avoiding the problems associated with oral or inhaled delivery. Ajulemic acid, a synthetic cannabinoid, binds to both the CB1 and CB2 receptors, and has shown benefit in a small neuropathic pain trial. It may have reduced psychological effects and is being studied for the treatment of interstitial cystitis.

Cannabinoid Receptor 2 Is Increased In Acutely And Chronically Inflamed Bladder Of Rats
Cannabinoid receptors 1 and 2 (CB1 and CB2) are G-protein coupled receptors that are expressed throughout the body. Cannabinoid receptor are expressed in the urinary bladder and may affect bladder function.

 

The purpose of this study was twofold:  to confirm the presence of cannabinoid receptors in the bladder, the L6/ S1 spinal cord, and dorsal root ganglia (DRG), and to determine the effects of acute and chronic bladder inflammation on expression of cannabinoid receptors. Acute or chronic bladder inflammation was induced in rats by intravesical administration of acrolein. Abundance of CB1 and CB2 protein and their respective mRNA was determined using immunoblotting and quantitative real-time PCR, respectively. We confirmed the presence of CB1 and CB2 receptor protein and mRNA in bladder, L6-S spinal cord, and DRG. Acute bladder inflammation induced increased expression of CB2, but not CB1, protein in the bladder detrusor. Chronic bladder inflammation increased expression of bladder CB2 protein and mRNA but not CB1 protein or mRNA. Expression of CB1 or CB2 in spinal cord or DRG was unaffected by acute or chronic bladder inflammation. CB1 and CB2 receptors are present in the bladder and its associated innervation, and CB2 receptors are up-regulated in bladder after acute or chronic inflammation. CB2 receptors may be a viable target for pharmacological treatment of bladder inflammation and associated pain.

Functional role of cannabinoid receptors in urinary bladder
In this study, we have shown that CB1 and CB2 are present in the bladder and its innervation, and that expression of CB2 is increased in the bladders of rats with acute and chronic cystitis. Bladder inflammation and pain is the summation of a number of biological events, including participation of the endocannabinoid system. The endocannabinoid system could play an important role in modulation of severity of bladder inflammation and pain, and it may be possible to take advantage of the cannabinoid system in the bladder to decrease inflammation and resultant pain.

Cannabinoid receptors in bladder
Cannabinoids, the active components of Cannabis sativa (maijuana), and their derivatives produce a wide spectrum of central and peripheral effects, some of which may have clinical applications. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to the general cannabinoid pharmacology.  In recent years, studies on the functional role of cannabinoid receptors in the  bladder have been motivated by the therapeutic effects of cannabinoids on voiding dysfunction in multiple sclerosis patients. In this review, we shall summarize the literature on the expression of cannabinoid receptors in urinary bladder and the peripheral influence of locally and systemically administered cannabinoids in the bladder. The ongoing search for cannabinoid-based therapeutic strategies devoid of psychotropic effects can be complemented with local delivery into bladder by the intravesical route. A greater understanding of the role of the peripheral CB(1) and CB(2) receptor system in lower urinary tract is necessary to allow the development of new treatment for pelvic disorders.

Recommendation:

Indica x Sativa hybrid
Whole plant extracts:  Cripple Creek (strain)

Vaporizer, Tinctures, Oils, Edibles, Cannabutter, Concoction

Timeless Tinctures

A Tincture is a medicinal extract in an alcohol solution.  The alcohol is used to extract and preserve the resins and other soluble material from the plant.  Cannabis tinctures are an excellent way to utilize the plant's medicinal ingredients and a perfect alternative for those who find smoking difficult.  Until the 1920's, Cannabis Indica tincture was  available at your neighborhood pharmacy (drug store).  Cannabis tinctures and extracts are commonly given as analgesics, sedatives and narcotics.  The philosophy behind tincture is to capture the spiritual and physical essence of the plant.  This is done by using the power of ethyl alcohol to dissolve and preserve the herb (cannabis).  Ethyl alcohol, known as ethanol, is used for countless applications.  Produced biologically by the fermentation of either sugar or starch, ethanol may be used as a solvent for organic chemicals, or as a starting compound for manufacturing dyes, drugs, perfumes and explosives.  Cannabis extraction requires high-proof spirits (90% pure grain alcohol) like Everclear.

References


Duke, J. A. 2000, Anti-aging Prescriptions. Rodale.
Hoffmann, D. 2000, The New Holistic Herbal. Element Pub.
McIntyre, A. 1995, The Complete Women's Herbal. Henry Holt Reference Books
Mills, S. Y. 1989, The A-Z of Modern Herbalism: A Comprehensive Guide to Practical Herbal Therapy. Thorson.
Shaw, N. 2002, Herbalism. Element
Tyler, Y. E. 1993, The Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. Haworth.
Woodward, P. 2003, Grow Your Own Herbal Remedies. Hyland House.

1. Bjorling DE, Elkahwaji JE, Bushman W, Janda LM, Boldon K, Hopkins WJ, Wang Z-Y. Acute acrolein-induced cystitis in mice. Brit J Urol Internat. 2007;99:1523–1529.
2. Bouaboula M, Rinaldi M, Carayon P, Carillon C, Delpech B, Shire D, Le Fur G, Casellas P. Cannabinoid-receptor expression in human leukocytes. Eur J Biochem. 1993;214:173–180. [PubMed]
3. Dinis P, Charrua A, Avelino A, Mohamed Y, Yaqoob M, Bevan S, Nagy I, Cruz F. Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. The Journal of Neuroscience. 2004;24:11253–11263. [PubMed]
4. Dmitrieva N, Berkley KJ. Contrasting effects of WIN 55212-2 on motility of the rat bladder and uterus. J Neurosci. 2002;22:7147–7153. [PubMed]
5. Dyson A, Peacock M, Chen A, Courade JP, Yaqoob M, Groarke A, Brain C, Loong Y, Fox A. Antihyperalgesic properties of the cannabinoid CT-3 in chronic neuropathic and inflammatory pain states in the rat. Pain. 2005;116:129–137. [PubMed]
6. Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A. Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci USA. 1995;92:3376–3380. [PMC free article] [PubMed]
7. Farquhar-Smith WP, Rice AS. Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder. Anesthesiology. 2001;94:507–513. [PubMed]
8. Gong JP, Onaivi ES, Ishiguro H, Liu QR, Tagliaferro PA, Brusco A, Uhl GR. Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res. 2006;1071:10–23. [PubMed]
9. Guerios SD, Wang Z-Y, Boldon K, Bushman W, Bjorling DE. Blockade of NGF and trk receptors inhibits increased peripheral mechanical sensitivity accompanying cystitis in rats. Am J Physiol Regul Integr Comp Physiol. 2008;295:111–122.
10. Hayn MH, Ballesteros I, de Miguel F, Coyle CH, Tyagi S, Yoshimura N, Chancellor MB, Tyagi P. Functional and Immunohistochemical Characterization of CB(1) and CB(2) Receptors in Rat Bladder. Urology. 2008 [Epub ahead of print]
11. Hegde VL, Hegde S, Cravatt BF, Hofseth LJ, Nagarkatti M, Nagarkatti PS. Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: Involvement of regulatory T cells. Mol Pharmacol. 2008;74:20–33. [PMC free article] [PubMed]
12. Hiragata S, Ogawa T, Hayashi Y, Tyagi P, Seki S, Nishizawa O, de Miguel F, Chancellor MB, Yoshimura N. Effects of IP-751, ajulemic acid, on bladder overactivity induced by bladder irritation in rats. Urology. 2007;70:202–208. [PubMed]
13. Jaggar SI, Sellaturay S, Rice ASC. The endogenous cannabinoid anadamide, but not the CB2 ligand palmitoylethanolamide, prevents the viscero-visceral hyperreflexia associated with inflammation of the rat urinary bladder. Neuroscience Letters. 1998;253:123–126. [PubMed]
14. Jaggar SI, Scott HCF, Rice ASC. Inflammation of the rat urinary bladder is associated with a referred hyperalgesia which is NGF dependent. Br J Anaesth. 1999;83:442–448. [PubMed]
15. Lim G, Sung B, Ji RR, Mao J. Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats. Pain. 2003;105:275–283. [PubMed]
16. Michalski CW, Laukert T, Sauliunaite D, Pacher P, Bergmann F, Agarwal N, Su Y, Giese T, Giese NA, Bátkai S, Friess H, Kuner R. Cannabinoids ameliorate pain and reduce disease pathology in cerulein-induced acute pancreatitis. Gastroenterology. 2007;132:1968–1978. [PMC free article] [PubMed]
17. Mitrirattanakul S, Ramakul N, Guerrero AV, Matsuka Y, Ono T, Iwase H, Mackie K, Faull KF, Spigelman I. Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain. Pain. 2006;126:102–114. [PMC free article] [PubMed]
18. Oddiah D, Anand P, McMahon SB, Rattray M. Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder. Neuroreport. 1998;9:1455–1458. [PubMed]
19. Pertwee RG, Fernando RS. Evidence for the presence of cannabinoid CB1 receptors in mouse urinary bladder. British Journal of Pharmacology. 1996;118:2053–2058. [PMC free article] [PubMed]
20. Piomelli D. The molecular logic of endocannabinoid signaling. Nat Rev Neurosci. 2003;4:873–884. [PubMed]
21. Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, Kendall DA, Scammell BE, Reeve AJ, Chapman V. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008;10:R43. [PMC free article] [PubMed]
22. Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 2005;310:329–332. [PubMed]
23. Wotherspoon G, Fox A, McIntyre P, Colley S, Bevan S, Winter J. Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons. Neuroscience. 2005;135:235–245. [PubMed]
24. Zhang J, Hoffert C, Vu HK, Groblewski T, Ahmad S, O'Donnell D. Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur J Neurosci. 2003;17:2750–2754. [PubMed] Bill H. McCarberg, MD, is founder of the Chronic Pain Management Program for Kaiser Permanente, San Diego, and assistant clinical professor in the Department of Family Practice at the University of California, San Diego, School of Medicine. He has served on the board of directors of the American Pain Society and currently is co-president of the Western Pain Society and a National Pain Foundation Advisor.
Bill H. McCarberg, MD, is founder of the Chronic Pain Management Program for Kaiser Permanente, San Diego, and assistant clinical professor in the Department of Family Practice at the University of California, San Diego, School of Medicine. He has served on the board of directors of the American Pain Society and currently is co-president of the Western Pain Society and a National Pain Foundation Advisor.

Traffic Roots Pixel