Neurourology and Urodynamics 25:379^380 (2006)

EDITORIALCOMMENT

Re: Gevaert T, Ost D, De Ridder D. 2006. Comparison Study ofAutonomous Activity in Bladders From Normal and Paraplegic

Rats. Neurourol Urodynam 25:368^378

The bladder is widely regarded as a subordinate of the CNS,reliant on instruction to determine the most fundamentalaspects of its function. However, the increasing number ofscienti¢c studies describing complex peripheral structures inthe bladder wall rather goes against this simple ‘‘slave model’’and sets some intriguing questions. If the bladder is only activewhen instructed by outside command, why should there beputative pacemaker cells in the detrusor [Smet et al., 1996;McCloskey and Gurney, 2002] and suburothelium [Sui et al.,2002; Wiseman et al., 2003]? If all that is needed is the relayingof commands, why should there be complex neural ganglia inthe bladder wall [Gabella, 1990]? Why is there a myovesicalplexus [Lagou et al., 2006]? Natural organisms are not givento expending hard-won nutrients on redundant structures;maybe the periphery should be given rather more credit thanit has thus far received in determining aspects of lower urinarytract function.

In this edition, Gevaert and colleagues describe an evalua-tion of pressure variations in the isolated rat bladder, compar-ing the activity of bladders after suprasacral spinal cord injurywith those from uninjured animals. They focus on adetailed description of low- and high-amplitude phasic activ-ity, respectively, termed ‘‘spikes’’and ‘‘macro-transients’’. Theydescribe a signi¢cantly lower frequency and larger amplitudeof macro-transients in bladders from paraplegic rats. Thesupposition is that the exaggeration of this activity bears a pas-sing resemblance to pressure waves characteristic of detrusoroveractivity. Similar observations in an animal model of detru-sor overactivity have been correlated with contractions a¡ect-ing an abnormally high proportion of the bladder wall, andsuggest an intrinsic mechanism to co-ordinate detrusor con-traction which becomes increasingly active in the pathophy-siological setting [Drake et al., 2001, 2003b]. Gevaert andcolleagues also describe increased spike activity. Again this isintriguing, since the wall movements associated with low-amplitude phasic pressure activity are typically highly loca-lised [Drake et al., 2003a], and might give rise to distortion ofthe bladder wall which could generate urgency sensations[Coolsaet et al., 1993].

Since the observations reported were made using isolatedwhole bladders, all movements must have an intrinsic origin,that is, they are autonomous. Furthermore, the degree ofcomplexity observed was more than that to be expectedfrom an organ which is a mere servant of the CNS. Theperipheral autonomy hypothesis comments on the physio-logical arrangement of regulatory structures of the bladder,and how alterations in their function may predictably giverise to detrusor overactivity. It was derived by applying tothe bladder, mechanisms originally described in the gastro-intestinal tract [Drake et al., 2001]. Put simply, it asserts thatthe myovesical plexus in the bladder integrates inputs fromdiverse sources to determine the likelihood of contractionof part or all of the bladder wall. In disease, the hypothesisproposes that various pathophysiological lesions increase thelikelihood of localised contraction, resulting in distortionand thus increased a¡erent activity and the sensation ofurgency. In addition, the potential for separate areas toco-ordinate their activity becomes greater, the simultaneouscontraction of a substantial part of the bladder therebygiving rise to overactive contractions. One of the conclusionsimplicit within the observations of Gevaert and colleaguesis the possibility of both co-ordinated macrotransients anduncoordinated spikes becoming more prevalent at thesame time. This suggests that they may have a di¡erentmechanistic basis, and may explain why detrusor overactivityand increased ¢lling sensation may manifest separately ortogether.The therapeutic relevance of the study by Gevaert and

colleagues lies in the possibility that purely peripheral

No con£ict of interest reported by the author(s).*Correspondence to: Marcus J. Drake, MA, DM, FRCS, Consultant Sur-geon, Bristol Urological Institute, Bristol BS10 5NB,United Kingdom.E-mail: marcus.drake@bui.ac.ukPublished online 7 July 2006 inWiley InterScience(www.interscience.wiley.com)DOI 10.1002/nau.20320

�2006Wiley-Liss, Inc.

mechanisms might underlie characteristic clinical observa-tions, viz. detrusor overactivity and increased a¡erent activity.Insight into the mechanisms giving rise to autonomousbladder activity may thus yield potential targets for develop-ment of novel treatments. The myovesical plexus is a termapplied to the interaction between interstitial cells and localinnervation within the bladder wall [Drake et al., 2001]. Earlyresults suggest that the interstitial cells are the structuresresponsible for autonomous bladder activity [Biers et al.,2006]. Furthermore, they lie in close proximity to nervesexpressing a characteristic pro¢le of neurotransmitters[Lagou et al., 2006]. The indications are, therefore, that themyovesical plexus may be nearly as fundamental to bladderfunction as the myenteric plexuses are for the gut. With theautonomous activity of the isolated bladder as a tool, study ofthe myovesical plexus and the integrative physiology of thedetrusor may thus yield valuable insight into normal andoveractive bladder function.

Marcus J. Drake*Bristol Urological InstituteBristol,United Kingdom

REFERENCES

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Coolsaet BL, Van Duyl WA,Van Os-Bossagh P, et al. 1993. New concepts inrelation to urge and detrusor activity. Neurourol Urodyn 12:463^71.

Drake MJ, Mills IW, Gillespie JI. 2001. Model of peripheral autonomousmodules and a myovesical plexus in normal and overactive bladder func-tion. Lancet 358:401^3.

DrakeMJ, Harvey IJ,Gillespie JI. 2003a. Autonomous activity in the isolatedguinea pig bladder. Exp Physiol 88:19^30.

Drake MJ, Hedlund P, Harvey IJ, et al. 2003b. Partial outlet obstructionenhances modular autonomous activity in the isolated rat bladder. J Urol170:276^79.

GabellaG. 1990. Intramural neurons in the urinary bladder of the guinea-pig.Cell Tissue Res 261:231^7.

Lagou M, deVente J, Kirkwood TB, et al. 2006. Location of interstitial cellsand neurotransmitters in the mouse bladder. BJU Int 97:1332^7.

McCloskey KD, GurneyAM. 2002. Kit positive cells in the guinea pig blad-der. J Urol 168:832^6.

Smet PJ, Jonavicius J, Marshall VR, et al. 1996. Distribution of nitric oxidesynthase-immunoreactive nerves and identi¢cation of the cellular targetsof nitric oxide in guinea-pig and human urinary bladder by cGMP immu-nohistochemistry. Neuroscience 71:337^48.

SuiGP, Rothery S,Dupont E, et al. 2002.Gap junctions and connexin expres-sion in human suburothelial interstitial cells. BJU Int 90:118^29.

Wiseman OJ, Fowler CJ, Landon DN. 2003. The role of the human bladderlamina propria myo¢broblast. BJU Int 91:89^93.

Neurourology and Urodynamics DOI 10.1002/nau

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