Onabotulinumtoxin-A intradetrusorial injections modulate bladder expression of NGF, TrkA, p75 and TRPV1 in patients with detrusor overactivity

Giannantoni, Antonella; Conte, Antonella; Farfariello, Valério; Proietti, Silvia; Vianello, A.; Nardicchi, Vincenza; Santoni, Giorgio; Amantini, Consuelo

doi:10.1016/j.phrs.2012.11.009

Cited by 28 publications

(22 citation statements)

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“…Reduced NGF immunofluorescence in detrusor following bladder wall injection of NGF antisense corroborates with the reported decrease in NGF after intradetrusor injection of botulinum toxin in OAB patients (Giannantoni et al, 2013). Bladder wall injection of NGF antisense is effective at 22 fold lower dose of ODN compared to intravesical instillation (Kashyap et al, 2013), which may prove to be cost effective when ODN is available in limited supply.…”

Section: Discussionsupporting

confidence: 87%

Constitutive expression Of NGF And P75NTR affected by bladder distension and NGF antisense treatment

et al. 2016

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Aims It is known that bladder exposure to noxious stimuli elicits nerve growth factor (NGF) expression with region wise differences. Here, we investigated the effect of bladder distension (cystometry) and bladder wall injection of NGF antisense oligonucleotide (ODN) together as well as separately on spontaneous (constitutive) expression of NGF and its cognate p75 neurotrophin receptor (p75NTR). Method Under isoflurane anesthesia, either 15µg of protamine sulfate (vehicle) alone or complexed with 1.5µg of NGF antisense or scrambled ODN was injected (10µL) at 4 sites in bladder wall of 24 adult female Sprague-Dawley rats and 6 rats were left untreated (n=30). Under urethane anesthesia, cystometry (CMG) was performed in treated and control rats. Fluorescent ODN and NGF/p75NTR expression was localized in harvested tissue. Key findings Complexation of ODN with protamine was essential for the retention of ODN in bladder tissue as the uncomplexed ODN was untraceable after injection. Bladder distension from CMG raised the expression of NGF and p75NTR relative to CMG naïve rats. The groups treated with vehicle, scrambled and antisense ODN were indistinct with regard to CMG parameters, but the intense immunoreactivity of NGF and p75NTR seen in the vehicle and scrambled ODN groups was reduced following treatment with NGF antisense. Significance The constitutive expression of NGF and p75NTR is responsive to bladder distension and administration of NGF antisense. Complexation with protamine reduces the clearance of ODN and demonstrates the potential of ODN nanoparticles as an option for reducing the inducible NGF expression in OAB patients following intradetrusor injection.

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Section: Discussionsupporting

confidence: 87%

Constitutive expression Of NGF And P75NTR affected by bladder distension and NGF antisense treatment

et al. 2016

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“…The TRPV1 receptors were found in the theca-interstitial cells of the follicles, with low expression at P10 that increased at the onset of pu-berty (FVO). These results are consistent with the expression of TRPV1 receptors in many tissues depending on cell type and activity [41,42]. In retina cells and pulmonary arterial smooth muscle cells, TRPV1 receptors promote cell proliferation and migration by MAPK intracellular signal activation [43,44].…”

Section: Discussionsupporting

confidence: 85%

Sensory denervation with capsaicin reduces ovarian follicular development and delays the onset of puberty in guinea pigs

Alatriste¹,

Herrera‐Camacho²,

Martínez³

et al. 2013

ARSci

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Introduction: It has been documented that mammalian ovaries receive sympathetic, parasympathetic and sensory nerve fibers. The aim of this work was to investigate the effects of sensory denervation with capsaicin at the first vaginal opening (FVO) on follicular development and the expression of TRPV1 receptors in ovary cells as well as in the dorsal root ganglia (DRGs) and lumbar dorsal spinal cord neurons of guinea pigs. The DRGs and lumbar dorsal spinal cord neurons serve as a nerve connection from the ovaries to the CNS. Materials and Methods: Female guinea pigs received a subcutaneous injection of capsaicin (30 mM) at 10 days of age (P10), while control animals were injected with vehicle. Using light microscopy, we counted healthy preantral follicles (HPF), healthy antral follicles (HAF), atretic preantral follicles (APF), and atretic antral follicles (AAF) in the ovaries at the FVO, and the numbers of TRPV1-positive cells were counted in the ovarian follicles, DRGs, and lumbar dorsal spinal cord (L2-L4) neurons by immunohistochemistry. Results: Guinea pigs treated with capsaicin showed a significant delay of FVO in comparison with the control animals (36 vs. 44 days). In the ovaries, the number of preantral and antral follicles decreased significantly. Additionally, the number of TRPV1-positive theca-interstitial cells of the antral follicles was reduced significantly, and the number of TRPV1-positive neurons in the DRGs and lumbar dorsal spinal cord (L2-L4) decreased. Thus, we showed that TRPV1 receptors throughout the sensory fibers modulate ovarian follicular development and the onset of puberty in guinea pigs. Conclusion: Sensory denervation decreases ovarian follicular development and delays the onset of puberty of guinea pigs. Our data support the idea that through TRPV1 receptors, ovarian afferent fibers sense local stimuli that are sent to the CNS.

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“…Even the least optimistic study still reported that 30% of NDO patients responded to treatment with RTX (Kuo, ). Interestingly, it was recently shown that botulinum toxin A, which is used as a second‐line treatment for NDO, reduced TRPV1 expression in bladder biopts of patients (Giannantoni et al ., ). This might indicate that, in addition to its known effects on the release of ACh by efferent neurons, reduction of TRPV1‐mediated afferent signals could contribute to the beneficial effects of botulinum toxin A in NDO patients.…”

Section: Lutd With Bladder Overactivitymentioning

confidence: 97%

TRP channels in lower urinary tract dysfunction

Franken

Uvin

Ridder

et al. 2014

British J Pharmacology

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Lower urinary tract dysfunction (LUTd) represents a major healthcare problem. Although it is mostly not lethal, associated social disturbance, medical costs, loss of productivity and especially diminished quality of life should not be underestimated. Although more than 15% of people suffer from a form of LUTd to some extent, pathophysiology often remains obscure. In the past 20 years, transient receptor potential (TRP) channels have become increasingly important in this field of research. These intriguing ion channels are believed to be the main molecular sensors that generate bladder sensation. Therefore, they are intensely pursued as new drug targets for both curative and symptomatic treatment of different forms of LUTd. TRPV1 was the first of its class to be investigated. Actually, even before this channel was cloned, it had already been targeted in the bladder, with clinical trials of intravesical capsaicin instillations. Several other polymodally gated TRP channels, particularly TRPM8, TRPA1 and TRPV4, also appear to play a prominent role in bladder (patho)physiology. With this review, we provide a brief overview of current knowledge on the role of these TRP channels in LUTd and their potential as molecular targets for treatment. LINKED ARTICLESThis article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx

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Onabotulinumtoxin-A intradetrusorial injections modulate bladder expression of NGF, TrkA, p75 and TRPV1 in patients with detrusor overactivity

Cited by 28 publications

References 28 publications

Constitutive expression Of NGF And P75NTR affected by bladder distension and NGF antisense treatment

Constitutive expression Of NGF And P75NTR affected by bladder distension and NGF antisense treatment

Sensory denervation with capsaicin reduces ovarian follicular development and delays the onset of puberty in guinea pigs

TRP channels in lower urinary tract dysfunction

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