The role of nerve growth factor in a model of visceral inflammation
Section snippets
Animal maintenance and surgery
This study was carried out on 59 female Wistar rats, weighing 225–260 g. The animals were anaesthetized with a single dose of urethane (1.25 g/kg, i.p.), which produced a stable level of anaesthesia lasting for the entire experiment. The trachea and one carotid artery were cannulated. Body temperature was measured and maintained close to 37°C. The bladder was catheterized transurethrally with a 1.1-mm polythene catheter. A ventral midline laparotomy was performed, enabling complete bladder
Results
The control cystometrograms in all treatment groups were similar. The average NC was low (3.1±0.3, n=59), as was the average TCT (157.3±13.8 s, n=59), while baseline MTs were moderately high (0.45±0.03 ml, n=59). Examples of representative cystometrograms are shown in Fig. 1, Fig. 5.
Discussion
In these experiments we set out to test the hypothesis that NGF functions as a mediator of sensory disorders associated with inflammation. A well-described model of cystitis in the rat was used.17, 18, 19, 33, 35Bladder reflex activity was studied, rather than, for instance, single afferent fibre activity, because it offers a robust measure of the integrated neuronal response to inflammation. Repeated measures can be made, allowing the time-course of effects to be conveniently studied. It is
Conclusions
Taken together, these findings suggest that our experimental observations may be relevant to some painful disorders of the urinary bladder in humans. The implication is that anti-NGF strategies may be of some therapeutic benefit in treating these clinical disorders.
Acknowledgements
This work was supported by a grant from the MRC of Great Britain. ND is supported by a studentship from CONICIT. We would also like to thank Caroline Abel, Tabitha Springhall and Sridhar Viswanathan for excellent technical help, and Paul Seed for statistical advice.
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