219 INHIBITORY EFFECT OF INTRATHECAL GALANIN ON THE MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS

INTRODUCTION AND OBJECTIVES: Galanin, a 29 amino acid peptide, distributes widely in the peripheral and central nervous systems, including the primary afferents, dorsal horn interneurons and the descending bulbospinal tracts. Recent studies have demonstrated that galanin is involved in nociceptive responses, especially in the transmission of nociceptive information in the spinal cord. However, it is not known whether galanin has a role in the control of the micturition reflex. Therefore, we investigated the effects of galanin on the micturition reflex in rats. METHODS: Continuous cystometrograms (CMG, 0.04ml/min infusion rate) were performed in female Sprague-Dawley rats (225–248 g) under urethane anesthesia. After stable micturition cycles were established, galanin was administered intrathecally to evaluate changes in bladder activity. In experiments examining the role of opioid systems, galanin was administered intrathecally when the first bladder contraction was observed after intrathecal administration of naloxone, an opioid receptor antagonist. Micturition parameters were recorded and compared before and after drug administration. RESULTS: Intrathecal administration of galanin at 1, 3 and 10 g (n 6 per dose) increased intercontraction intervals in a dosedependent fashion to 117.7 2.4%, 141.1 7.8% and 159.8 12.5% of the control value, respectively (p 0.01). These inhibitory effects were seen immediately after administration and returned to the precontrol level within 70 minutes. Intrathecal administration of galanin at 1, 3 and 10 g (n 6 per dose) also increased pressure thresholds in a dose-dependent fashion to 9.52 0.98 cmH2O, 11.2 1.12 cmH2O and 12.9 1.67 cmH2O, respectively (p 0.01). There were no significant changes in baseline pressure or residual urine at any doses tested. These inhibitory effects of galanin (10 g, n 6) were antagonized by intrathecal administration of naloxone (10 g, n 6). CONCLUSIONS: These results indicate that in urethane-anesthetized rats galanin inhibits the micturition reflex through the opioid mechanism. Thus, galanin could be effective for the treatment of bladder dysfunction such as overactive bladder.