Effect of capsaicin on the micturition reflex  in normal and chronic spinal cord-injured cats

Cheng, Chen-Li; Liu, Jiang-Chuan; Chang, Sun‐Yran; Ma, Cheng‐Ping; Groat, William C. de

doi:10.1152/ajpregu.1999.277.3.r786

Cited by 56 publications

(65 citation statements)

References 23 publications

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“…The TRPV1 agonist, capsaicin (trans-8-methyl-N-vanilly-6-nonenamide), has been used to desensitize a subpopulation of small-diameter, unmyelinated C-fiber afferents that innervate the bladder, leav- ing the other afferents unaffected (Barbanti et al, 1993;de Groat, 1993). In animals pretreated with capsaicin (100 mg/kg s.c.), 4 days before the experiment, there was no significant change in bladder contraction amplitude or intercontraction interval in the cystometrograms of rats perfused with saline as previously reported (Cheng et al, 1999). In these rats, 4␣-PDD still significantly increased peak intravesical voiding pressures (41 Ϯ 6%, n ϭ 5) (Fig.…”

Section: ␣-Pdd Augments Bladder Contraction Via a Capsaicin-insensitsupporting

confidence: 80%

Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4α-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat

Birder

Kullmann

Lee

et al. 2007

J Pharmacol Exp Ther

130

144

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The ion channel transient receptor potential vanilloid (TRPV) 4 can be activated by hypo-osmolarity, heat, or certain lipid compounds. Here, we demonstrate expression of functional TRPV4 protein in the urothelium lining the renal pelvis, ureters, urinary bladder, and urethra. Exposure of cultured rat urothelial cells from the urinary bladder to the TRPV4-selective agonist 4␣-phorbol 12,13-didecanoate (4␣-PDD) promoted Ca 2ϩ influx, evoked ATP release, and augmented the ATP release evoked by hypo-osmolarity. In awake rats during continuous infusion cystometrograms, intravesical administration of 4␣-PDD (10 -100 M) increased maximal micturition pressure by 51%, specifically by augmenting the portion of each intravesical pressure wave that follows high-frequency urethral oscillations and voiding. This unusual pharmacological effect was prevented by intravesical pretreatment with the nonselective ATP receptor antagonist, pyridoxal phosphate-6-azophenyl-2Ј,4Ј-disulfonic acid (100 M), systemic treatment with the selective P2X 3 purinergic antagonist 5- ([(3-phenoxybenzyl)[1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl)-1,2,4-benzenetricarboxylic acid (A317491) (250 mol/kg), or urethane anesthesia, but was unaffected by capsaicin pretreatment (100 mg/kg s.c.) or denervation of the urethral sphincter. 4␣-PDD (1-100 M) did not alter the contractility to electrical stimulation of excised bladder strips. We conclude that activation of urothelial TRPV4 by 4␣-PDD and release of mediators such as ATP trigger a novel neural mechanism that regulates the late phase of detrusor muscle contraction after micturition. These data raise the possibility that TRPV4 channels in the urothelium could contribute to abnormal bladder activity.

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Section: ␣-Pdd Augments Bladder Contraction Via a Capsaicin-insensitsupporting

confidence: 80%

Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4α-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat

Birder

Kullmann

Lee

et al. 2007

J Pharmacol Exp Ther

130

144

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“…Detrusor relaxation was likely caused by inhibition of the A␦-fiber-mediated micturition reflex via reflex activation of sympathetic hypogastric efferents (at low intravesical pressure) or inhibition of pelvic efferents (at high intravesical pressure) (18,32). The micturition reflex after chronic SCI is mainly mediated by c-fiber bladder afferents (8,13,16), but stimulation of the DGN can inhibit both the A␦-and the c-fibermediated reflexes (36).…”

Section: Discussionmentioning

confidence: 99%

Activation and inhibition of the micturition reflex by penile afferents in the cat

Woock

Yoo²,

Grill³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Woock JP, Yoo PB, Grill WM. Activation and inhibition of the micturition reflex by penile afferents in the cat. Am J Physiol Regul Integr Comp Physiol 294: R1880-R1889, 2008. First published April 23, 2008 doi:10.1152/ajpregu.00029.2008.-Coordination of the urinary bladder and the external urethral sphincter is controlled by descending projections from the pons and is also subject to modulation by segmental afferents. We quantified the effects on the micturition reflex of sensory inputs from genital afferents traveling in the penile component of the somatic pudendal nerve by electrical stimulation of the dorsal nerve of the penis (DNP) in ␣-chloralose anesthetized male cats. Depending on the frequency of stimulation (range, 1-40 Hz), activation of penile afferents either inhibited contractions of the bladder and promoted urine storage or activated the bladder and produced micturition. Stimulation of the DNP at 5-10 Hz inhibited distension-evoked contractions and increased the maximum bladder capacity before incontinence. Conversely, stimulation at 33 and 40 Hz augmented distension-evoked contractions. When the bladder was filled above a threshold volume (70% of the volume necessary for distension-evoked contractions), stimulation at 20 -40 Hz activated de novo the micturition reflex and elicited detrusor contractions that increased voiding efficiency compared with distension-evoked voiding. Electrical stimulation of the DNP with a cuff electrode or percutaneous wire electrode produced similar results. The ability to evoke detrusor contractions by activation of the DNP was preserved following acute spinal cord transection. These results demonstrate a clear role of genital afferents in modulating the micturition reflex and suggest the DNP as a potential target for functional restoration of bladder control using electrical stimulation. electrical stimulation; spinal cord injury; dorsal nerve of the penis; frequency dependence RECIPROCAL COORDINATION of the urinary bladder and the external urethral sphincter (EUS) to maintain continence and produce micturition is controlled by the pontine micturition center (2, 3, 24). The spinobulbospinal micturition reflex is also subject to modulation by peripheral afferent activity (29, 30) that can influence voiding efficiency (41). The objective of the present study was to quantify the effects of genital afferents traveling in the penile component of the somatic pudendal nerve on the micturition reflex in the cat.Activation of pudendal afferent nerve fibers can engage spinal (5) and spinobulbospinal (2, 3) reflexes that are integral to the regulation of bladder function. Fluid flow through the urethra activates pudendal afferents (56), and this flow-driven activation can elicit detrusor contractions and facilitate micturition (2, 44, 48). Furthermore, electrical stimulation of pudendal urethral afferents in the cat (5, 49) and human (21) elicits detrusor contraction, and these responses are preserved following decerebration and acute and chronic spinal cord transection (SCT;...

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“…Cats also appear to have a true spinal micturition reflex [33,34,42], and the NVPMCs of SCT cats are also vanilloid sensitive [42], as in the rat. However, unlike the rat, there does seem to be vanilloid sensitivity to the spinal micturition reflex as well following SCT, suggesting that the reflex in SCT animals has a stronger C-fiber component.…”

Section: Urodynamic Patterns In Spinal Cord-transected Animalsmentioning

confidence: 99%

New Insights into the Pathophysiology of Detrusor-Sphincter Dyssynergia

Fraser

2011

Curr Bladder Dysfunct Rep

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Detrusor-sphincter dyssynergia (DSD) is a condition in which the urethral outlet actively contracts during a detrusor contraction. This is most often caused by isolated and complete suprasacral spinal cord lesions and can be manifested by external urethral sphincter (EUS) or bladder neck/ proximal urethral smooth muscle contraction, or both, reflexly generated against a hyperreflexive detrusor contraction. The resultant generation of high intravesical pressures, if left untreated, can cause damage to the bladder itself and result in ureteral reflux, hydronephrosis, and renal failure. Current therapies solve some problems but do not address the underlying pathology. Thus, understanding the pathophysiology underlying EUS DSD remains a priority in the urologic care of patients with suprasacral transverse spinal myelopathies. This review examines data and concepts from animals and humans to elucidate the pathophysiology of EUS DSD.

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Effect of capsaicin on the micturition reflex in normal and chronic spinal cord-injured cats

Cited by 56 publications

References 23 publications

Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4α-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat

Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4α-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat

Activation and inhibition of the micturition reflex by penile afferents in the cat

New Insights into the Pathophysiology of Detrusor-Sphincter Dyssynergia

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