2006
DOI: 10.1523/jneurosci.3023-06.2006
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Bladder Overactivity and Hyperexcitability of Bladder Afferent Neurons after Intrathecal Delivery of Nerve Growth Factor in Rats

Abstract: Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 g/l) was infused continuously into the intrathecal space at the L6 -S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 l/h). Bladder afferent ne… Show more

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Cited by 154 publications
(182 citation statements)
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“…Furthermore, several studies have shown that the arbours of small-diameter primary C-fibre afferents can enlarge greatly in rats and mice after SCI potentially leading to increased reflex excitation of preganglionic neurons, via interneuronal pathways. 15 These afferent neurons are CGRP-immunoreactive, and are believed to mediate the spinal reflex pathways to the sympathetic preganglionic neurons, and hence play a significant role in the pathogenesis of NDO. 11,15 …”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Furthermore, several studies have shown that the arbours of small-diameter primary C-fibre afferents can enlarge greatly in rats and mice after SCI potentially leading to increased reflex excitation of preganglionic neurons, via interneuronal pathways. 15 These afferent neurons are CGRP-immunoreactive, and are believed to mediate the spinal reflex pathways to the sympathetic preganglionic neurons, and hence play a significant role in the pathogenesis of NDO. 11,15 …”
Section: Discussionmentioning
confidence: 99%
“…15 These afferent neurons are CGRP-immunoreactive, and are believed to mediate the spinal reflex pathways to the sympathetic preganglionic neurons, and hence play a significant role in the pathogenesis of NDO. 11,15 …”
Section: Discussionmentioning
confidence: 99%
“…NGF levels can be reduced along with symptom improvement after intradetrusor botulinum toxin treatment (231,385). Animal studies also demonstrated that the production of neurotrophic factors including NGF increases in the bladder after SCI (661) and chronic administration of NGF into the spinal cord or into the bladder wall in rats induces bladder overactivity and increases excitability of bladder afferent neurons (366,698,740). Increased transport of NGF to DRG cell bodies or central NGF production in the injured spinal cord could modulate the micturition pathway at the spinal level.…”
Section: Disease-induced Changes In Micturition Spinal Cord Injury Anmentioning
confidence: 99%
“…In a rat model of chronic cystitis, increased expression of neurotrophic factors (NGF, BDNF, and CTNF) in the bladder as well as phosphorylation of tyrosine kinase receptors (TrkA and TrkB) in bladderinnervating afferent neurons have been detected providing evidence for a contribution of neurotrophin-mediated signaling to chronic bladder inflammation (512,659). It has also been demonstrated that exogenous NGF can induce bladder nociceptive responses and bladder overactivity in rats when applied acutely into the bladder lumen (114,192) or chronically to the bladder wall or intrathecal space (366,698). Moreover, it has been shown that an application of NGF sequestering molecules (trkA-IgG or REN1180) can reduce a referred thermal hyperalgesia elicited by bladder inflammation using turpentine oil (288) or bladder overactivity elicited by CYP-induced cystitis (277).…”
Section: Inflammation/bladder Pain Syndromementioning
confidence: 99%
“…3 In addition, the expression of TRP channels such as TRPV1 and TRPA1 are involved in the sensitization of C-fiber afferent pathways. 4 Previous studies have also indicated that increased levels of nerve growth factor (NGF) in the bladder is one of the key mediators to induce hyperexcitability of C-fiber bladder afferent pathways after SCI, resulting in detrusor overactivity (DO), [5][6][7][8] and that intrathecal application of NGF antibodies, which reduces NGF levels in bladder afferent pathways, is effective for DO as well as AD in SCI rats. [9][10][11] A recent study demonstrated that the intravesical treatment with botulinum toxin also reduces AD induced by bladder contractions, which is associated with a reduction in NGF levels in the whole bladder tissue and dorsal root ganglia (DRG).…”
Section: Introductionmentioning
confidence: 99%