Cannabinoid agonist may reduce cystitis severity, according to study

October 18, 2013

Results from a study in an experimental model of cystitis point to the cannabinoid receptor 2 (CB2) as a potential target to develop effective new therapies for patients with painful bladder disorders.

Madison, WI-Results from a study in an experimental model of cystitis point to the cannabinoid receptor 2 (CB2) as a potential target to develop effective new therapies for patients with painful bladder disorders.

First author Zunyi Wang, PhD, and colleagues at the University of Wisconsin, Madison investigated the effects of a selective CB2 agonist, GP1a, in mice with cystitis induced by intravesical instillation of acrolein. Compared with vehicle control, GP1a reduced the severity of the cystitis as well as attenuated the mechanical hyperalgesia and increased urination frequency associated with the bladder inflammation. In addition, the benefits of the CB2 agonist were mitigated by pretreatment with a CB2 antagonist.

“Cannabinoids exert potent analgesic and anti-inflammatory effects, and it is known that CB2 is expressed in the bladder, especially in urothelial cells, which we confirmed in our mouse model by immunohistochemistry,” said Dr. Wang, associate scientist in the University of Wisconsin’s School of Veterinary Medicine.

“The data from this model indicate that CB2 activation inhibits bladder inflammation and the associated bladder hyperreactivity and visceral pain,” added Dr. Wang, who presented the findings at the AUA annual meeting in San Diego.

In the study, groups of animals had saline or acrolein instilled in the bladder and then received GP1a or vehicle by intraperitoneal administration after 3, 24, and 30 hours. In addition, some animals were given a CB2 antagonist, AM630, 10 minutes prior to GP1a or vehicle.

Sensitivity of the hind paws (referred hyperalgesia) was assessed as an indicator for visceral pain by application of a mechanical stimulus at 3, 24, and 48 hours after intravesical instillation of acrolein or saline. Urination frequency was evaluated by assaying filter paper spotting after 24 hours.

Treatment inhibits sensitivity

The results showed acrolein enhanced the mechanical sensitivity of the animals’ hind paws and caused an increase in urination frequency. These effects were inhibited by treatment with GP1a, whereas the inhibitory effects of GP1a on both endpoints were reversed by AM630 pretreatment.

In addition, animals were sacrificed after 48 hours and the bladders were removed for weighing and histologic evaluation. The assessments showed evidence of acrolein-induced cystitis characterized by edema in the submucosal region and infiltration of inflammatory cells. Consistent with the edema, bladder weight was significantly increased in the acrolein-treated animals compared with the saline-treated controls.

Treatment with GP1a ameliorated the acrolein-induced changes in the bladder, but the benefit of GP1a was reversed by pretreatment with the CB2 antagonist.UT

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