Constitutive expression Of NGF And P75(NTR) affected by bladder distension and NGF antisense treatment

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 (p75(NTR)).

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/p75(NTR) expression was localized in harvested tissue.

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 p75(NTR) 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 p75(NTR) seen in the vehicle and scrambled ODN groups was reduced following treatment with NGF antisense.

The constitutive expression of NGF and p75(NTR) 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.