Increased expression of neuronal nitric oxide synthase in bladder afferent cells in the lumbosacral dorsal root ganglia after chronic bladder outflow obstruction

Zvara, Peter; Folsom, Jeffrey B.; Kliment, J.; Dattilio, Abbey; Moravčı́ková, Adriana; Plante, Mark; Vizzard, Margaret A.

doi:10.1016/j.brainres.2003.12.016

Cited by 12 publications

(8 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The spinal reflex was found promoted in the BOO rats similar to the chronic spinalized animals 25. With this reflex, the bladder contraction could be activated at small volume but insufficient to trigger the supraspinal micturition reflex.…”

Section: Discussionmentioning

confidence: 81%

Bladder mechanoreceptor changes after artificial bladder outlet obstruction in the anesthetized rat

Zeng

Xie

Jiang

et al. 2011

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 81%

Bladder mechanoreceptor changes after artificial bladder outlet obstruction in the anesthetized rat

Zeng

Xie

Jiang

et al. 2011

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

“…Several animal models of peripheral nerve injury [ 54 , 57 – 59 ], including spinal cord injury have shown increases in nNOS expression shortly after the peripheral insult. Differential regulation of nNOS expression during disease progression were also reported between lumbar and sacral DRG [ 51 , 52 , 60 ]. These data suggested that nNOS expression is very dynamic and possibly regulated by peripheral nerve activity.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic inhibition of lumbosacral sensory neurons alleviates visceral hypersensitivity in a mouse model of chronic pelvic pain

et al. 2022

View full text Add to dashboard Cite

The study investigated the cellular and molecular mechanisms in the peripheral nervous system (PNS) underlying the symptoms of urologic chronic pelvic pain syndrome (UCPPS) in mice. This work also aimed to test the feasibility of reversing peripheral sensitization in vivo in alleviating UCPPS symptoms. Intravesical instillation of vascular endothelial growth factor A (VEGFA) was used to induce UCPPS-like symptoms in mice. Spontaneous voiding spot assays and manual Von Frey tests were used to evaluate the severity of lower urinary tract symptoms (LUTS) and visceral hypersensitivity in VEGFA-instilled mice. Bladder smooth muscle strip contractility recordings (BSMSC) were used to identify the potential changes in myogenic and neurogenic detrusor muscle contractility at the tissue-level. Quantitative real-time PCR (qPCR) and fluorescent immunohistochemistry were performed to compare the expression levels of VEGF receptors and nociceptors in lumbosacral dorsal root ganglia (DRG) between VEGFA-instilled mice and saline-instilled controls. To manipulate primary afferent activity, Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADD) were expressed in lumbosacral DRG neurons of TRPV1-Cre-ZGreen mice via targeted adeno-associated viral vector (AAVs) injections. A small molecule agonist of Gi-DREADD, clozapine-N-oxide (CNO), was injected into the peritoneum (i. p.) in awake animals to silence TRPV1 expressing sensory neurons in vivo during physiological and behavioral recordings of bladder function. Intravesical instillation of VEGFA in the urinary bladders increased visceral mechanical sensitivity and enhanced RTX-sensitive detrusor contractility. Sex differences were identified in the baseline detrusor contractility responses and VEGF-induced visceral hypersensitivity. VEGFA instillations in the urinary bladder led to significant increases in the mRNA and protein expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) in lumbosacral DRG, whereas the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1) and VEGF receptors (VEGFR1 and VEGFR2) remained unchanged when compared to saline-instilled animals. Importantly, the VEGFA-induced visceral hypersensitivity was reversed by Gi-DREADD-mediated neuronal silencing in lumbosacral sensory neurons. Activation of bladder VEGF signaling causes sensory neural plasticity and visceral hypersensitivity in mice, confirming its role of an UCPPS biomarker as identified by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research studies. Pharmacogenetic inhibition of lumbosacral sensory neurons in vivo completely reversed VEGFA-induced pelvic hypersensitivity in mice, suggesting the strong therapeutic potential for decreasing primary afferent activity in the treatment of pain severity in UCPPS patients.

show abstract

“…Furthermore, it has been demonstrated (Lecci et al, 1994) that intrathecal injection of sub P antagonists reduced bladder inflammation-induced bladder hyperreflexia. Much less is known regarding the contribution of nNOS to urinary bladder dysfunction; however, BOO is associated with increased nNOS expression in bladder afferent neurons in DRG (Zvara et al, 2004). Therefore, PACAP, VIP, sub P and nNOS signaling in the urinary bladder, sensory neurons and/or MPG may represent diverse sites for neuromodulation of bladder function in SYN-OE mice.…”

Section: Discussionmentioning

confidence: 99%

“…We sought to determine if components of the micturition reflex pathways in SYNOE mice exhibited changes in transcript expression of neuroactive compounds including neuropeptides (e.g., pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), substance P (sub P) and neuronal nitric oxide synthase (nNOS)) previously shown to be altered with urinary bladder dysfunction (Lecci et al, 1994; Zvara et al, 2004; Braas et al, 2006; Girard et al, 2008; Studeny et al, 2008; May and Vizzard, 2010; Tompkins et al, 2010). In addition, we determined expression of human α-SYN and endogenous mouse α-SYN in tissues from micturition pathways, superior cervical ganglia (SCG) and brain from WT and SYN-OE mice.…”

Section: Methodsmentioning

confidence: 99%

Autonomic dysfunction and plasticity in micturition reflexes in human α‐synuclein mice

Hamill

Tompkins

Girard

et al. 2012

Developmental Neurobiology

View full text Add to dashboard Cite

Although often overshadowed by the motor dysfunction associated with Parkinson’s disease (PD), autonomic dysfunction including urinary bladder and bowel dysfunctions are often associated with PD and may precede motoric changes; such autonomic dysfunction may permit early detection and intervention. Lower urinary tract symptoms are common in PD patients and result in significant morbidity. The current studies focus on non-motor symptoms in PD using a transgenic mouse model with overexpression of human α-synuclein, the peptide found in high concentrations in Lewy body neuronal inclusions, the histopathologic hallmark of PD. We examined changes in the physiological, molecular, chemical, and electrical properties of neuronal pathways controlling urinary bladder function in transgenic mice. The results of these studies reveal that autonomic dysfunction (i.e., urinary bladder) can precede motor dysfunction. In addition, mice with human α-synuclein overexpression in relevant neuronal populations is associated with alterations in expression of neurotransmitter/ neuromodulatory molecules (PACAP, VIP, substance P, neuronal NOS) within neuronal pathways regulating bladder function as well as with increased NGF expression in the urinary bladder. Changes in the electrical and synaptic properties of neurons in the major pelvic ganglia that provide postganglionic innervation to urogenital tissues were not changed as determined with intracellular recording. The urinary bladder dysfunction observed in transgenic mice likely reflects changes in peripheral (i.e., afferent) and/or central micturition pathways or changes in the urinary bladder. SYN-OE mice provide an opportunity to examine early events underlying the molecular and cellular plasticity of autonomic nervous system pathways underlying synucleinopathies.

show abstract

Increased expression of neuronal nitric oxide synthase in bladder afferent cells in the lumbosacral dorsal root ganglia after chronic bladder outflow obstruction

Cited by 12 publications

References 36 publications

Bladder mechanoreceptor changes after artificial bladder outlet obstruction in the anesthetized rat

Bladder mechanoreceptor changes after artificial bladder outlet obstruction in the anesthetized rat

Pharmacogenetic inhibition of lumbosacral sensory neurons alleviates visceral hypersensitivity in a mouse model of chronic pelvic pain

Autonomic dysfunction and plasticity in micturition reflexes in human α‐synuclein mice

Contact Info

Product

Resources

About