Article ID Journal Published Year Pages File Type
3477471 Journal of the Chinese Medical Association 2007 6 Pages PDF
Abstract

BackgroundTo investigate the effect of a selective P2X3–P2X2/3 purinergic receptor antagonist (A-317491) on detrusor hyperreflexia in conscious chronic spinal cord-injured female rats.MethodsSix chronic spinal cord-transected female Sprague-Dawley rats (290–336 g) were used in this study. Spinal transection at the T8–T9 segmental level was performed using aseptic techniques under halothane anesthesia. Fourteen to 16 weeks after spinal transection, A-317491, a selective P2X3 purinergic receptor antagonist, was administered intravenously in cystometry studies at increasing doses of 0.03, 0.1, 0.3, 1, 3, 10 and 30 mmol/kg at 40–50 minute intervals. Cystometrograms (CMGs) were performed before and after the administration of each dose of the drug.ResultsThe continuous filling of CMGs revealed a large number of small-amplitude (> 8 cmH2O), non-voiding contractions (NVCs) (average, 9.7 per voiding cycle) preceding voiding contractions (mean amplitude, 31 cmH2O; duration, 2.5 minutes), which occurred at an interval of 539 seconds and at a pressure threshold of 5.7 cmH2O. When tested in a range of doses (0.03–30 μmol/kg, intravenous), A-317491 in doses between 1 and 30 mmol/kg significantly (p < 0.05) increased the interval between voids by 25%, reduced the number of NVCs by 42–62%, and increased the pressure threshold for voiding by 53–73%, but did not change the amplitude of the duration of the voiding contractions. The effects of the drug were apparent within 10 minutes following administration.ConclusionThese results indicate that purinergic mechanisms, presumably involving P2X3 or P2X2/3 receptors on bladder C-fiber afferent nerves, play an important role in the detrusor hyperreflexia that occurs after spinal cord injury in rats.

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