Structural and Functional Denervation of Human Detrusor after Spinal Cord Injury

Drake, Marcus; Hedlund, Petter; Mills, Ian W.; McCoy, Rachel; McMurray, Gordon; Gardner, Brett O.; Andersson, Karl Erik; Brading, Alison F.

doi:10.1038/labinvest.3780158

Cited by 56 publications

(49 citation statements)

References 34 publications

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“…Supporting this, Smet et al (1997) found that the density of CGRP and SP-immunoreactive nerves within the subepithelium was increased by 82% in women with urodynamically proven detrusor overactivity compared with control without any lower urinary tract symptoms. In patients with spinal cord injury, the subepithelial nerve plexus and its density of CGRPcontaining nerves were reduced (Drake et al, 2000).…”

Section: Peripheral Targetsmentioning

confidence: 99%

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Andersson

Wein²

2004

Pharmacol Rev

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455

364

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Section: Peripheral Targetsmentioning

confidence: 99%

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Andersson

Wein²

2004

Pharmacol Rev

Self Cite

455

364

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“…A few groups have already demonstrated striking structural characteristics and functional potential of bladder ICs. [1][2][3] Nerve ganglia in the bladder wall and in the pelvic plexus contain multitudinous connections, and express a diverse range of putative transmitters; [4][5][6] current understanding of their functional properties is limited.…”

Section: Cellular Phenotypes Present In the Bladdermentioning

confidence: 99%

The Integrative Physiology of the Bladder

Drake

2007

annals

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Some years ago, a drug was available for use in patients who failed to pass urine after a catheter was removed, in the hope that it would aid return of normal voiding. The drug, bethanechol, was a logical choice in this context, because the parasympathetic nerves supplying the bladder release acetylcholine to make the detrusor muscle contract. Giving a drug that stimulates the detrusor muscle in the same way, it was thought, should increase bladder tone and so re-establish voiding. Sadly, the clinical outcome was usually disappointing, resulting in suprapubic discomfort and a stubborn persistence of urinary retention. The experience with bethanechol is illuminating, as it illustrates a failure to grasp the fundamental complexity of bladder function; the specific weakness lies in the fallacy that whole bladder function can be extrapolated from any individual cell type (in the case of bethanechol, the smooth muscle). Integrative physiology, the study of how intact tissue behaves, focuses on the cellular interactions; these appear to be fundamental to a clear understanding of normal bladder function and the pathophysiological changes underpinning clinical lower urinary tract problems. The clinical settingThe normal bladder has storage and voiding phases, the onset of the latter being determined by the pontine micturition centre in the brainstem. Clinical problems affecting urine storage are highly prevalent, and result in urinary urgency, frequency and urgency incontinence. They are commonly associated with detrusor overactivity (DO), which is the presence of inappropriate detrusor contractions detected during pressure cystometry while the bladder is being filled. Voiding problems also show a high prevalence, and result in a weak urinary stream and incomplete bladder emptying, the latter detectable as the presence of a post voiding residual volume (PVR). Improved understanding of the mechanisms underlying these problems is desirable, as current management options available are only effective in a proportion of cases and can carry significant risk of adverse effects. Cellular phenotypes present in the bladderUnderstanding cell interactions is a challenge, because the bladder wall, perhaps a little unexpectedly, has quite a complicated structure. Tw o particularly interesting cell classes are the interstitial cells (ICs) and the peripheral neurones. The existence of bladder ICs was only recently established, but they have spawned much interest, since they appear to share some of the properties of the interstitial cells of Cajal (ICCs) in the gut. Since the ICCs ABSTRACT Normal bladder function is complex, resulting from the co-operative interaction of numerous regulatory cell types, of which the interstitial cells and the peripheral neurones are particularly interesting. Collectively, these comprise the myovesical plexus, which appears to confer structural and functional characteristics on the bladder loosely akin to those of the gut. These include functional modularity, which gives rise to the potential for localise...

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“…75 Galanin is widely distributed in enteric nerve terminals and acts to modulate intestinal motility by altering smooth muscle contraction and in the human colon, alterations in Gal1-R expression may have an important role in colitis. 76 Indeed, inflammation up-regulates this receptor by an NF-B-dependent pathway.…”

Section: Galanin R1mentioning

confidence: 99%

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

Saban

Nguyen

Hammond

et al. 2002

The American Journal of Pathology

110

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Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and isClinical and animal models of acute and chronic urinary bladder inflammation have provided several lines of evidence suggesting a central role of mast cells, sensory nerves, and neurokinin (NK)-1 receptors. Fundamental work regarding the participation of sensory nerves and mast cells in cystitis provides indirect evidence, such as increased numbers of mast cells in the detrusor and submucosa, and morphological evidence of mast cell activation and degranulation. [1][2][3][4] In addition, the extensive tissue remodeling seen in some clinical forms of bladder inflammation such as interstitial cystitis, 4 along with increased urinary levels of histamine and tryptase 5 suggest a role for mast cells. Because both mast cells 6 -8 and NK-1 receptors are increased in bladder biopsies of interstitial cystitis (IC) patients, 9,10 it is tempting to propose a role for sensory peptides-mast cell communication in the pathogenesis of this disorder.Experimentally, we have used classical morphometric analysis and microarray technology to determine the role of mast cells, NK-1 receptors, and bacterial toxins in animal models of cystitis. Time-course experiments indicated early and late genes involved in bladder inflammatory responses. 11 The availability of mice genetically deficient in neurokinin-1 receptor (NK-1R Ϫ/Ϫ ) allowed us to propose a mandatory role of SP receptors in cystitis. 12 We also determined genes that depend on the presence of tissue mast cells for their expression by comparing inflammatory responses in mast cell-deficient (Kit W /

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Structural and Functional Denervation of Human Detrusor after Spinal Cord Injury

Cited by 56 publications

References 34 publications

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

The Integrative Physiology of the Bladder

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

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