期刊
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
卷 166, 期 1-2, 页码 35-38出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.autneu.2011.09.005
关键词
TRPV1; Urinary bladder; GRC 6211; Spinalization; Bladder overactivity
资金
- INComb FP7 HEALTH [223234]
Purpose: To evaluate the effect of a transient receptor potential vanilloid 1 (TRPV1) antagonist GRC 6211 on neurogenic detrusor overactivity (NDO) of spinal origin. Materials and methods: Cystometries under urethane anaesthesia were obtained in 14 chronic spinalized rats to confirm NDO. Two groups were created. In the first one (n = 10), GRC 6211 (0.01, 0.1 and 1 mg/kg weight) was administered via the duodenum in cumulative doses and cystometries performed 150 min after the administration of each dose of the drug. In the second group (n = 4), used as control, the animals were submitted to cystometries during 12 hours, without administration of GRC 6211. Frequency and amplitude of bladder contractions were recorded in both groups. Results: The mean (+/- SDev) bladder detrusor muscle contraction frequency of spinalized rats was 0.7 +/- 0.27 contractions/min. GRC 6211 produced a significant dose-dependent effect, with the frequency diminished to 0.53 +/- 0.23, 0.40 +/- 0.20 and 0.20 +/- 0.13 contractions/min, respectively. The mean (+/- SDev) amplitude of bladder contractions was 48.4 +/- 4.4 cmH(2)O. After administration of 0.01 mg/kg, 0.1 mg/kg and 1 mg/kg of GRC 6211, the amplitude decreased to 47.1 +/- 4.3, 45.6 +/- 5.6 and 40.2 +/- 4.1 cmH(2)O respectively. The effect was significant at 0.1 and 1 mg/kg doses. Cystometries performed in the control group of spinalized rats showed no evidence of detrusor fatigue caused by the urethane anaesthesia and long duration of the experiment. Conclusion: TRPV1 antagonists may be very effective in reducing NDO of spinal origin. This finding may have profound implications for the pathogenesis and future treatment options of patients with spinal NDO. (C) 2011 Elsevier B.V. All rights reserved.
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