BOTULINUM-A TOXIN INJECTIONS INTO THE DETRUSOR MUSCLE REDUCE NERVE GROWTH FACTOR BLADDER TISSUE LEVELS IN P A TIENTS AFFECTED BY NEUROGENIC DETRUSOR OVER- ACTIVITY

INTRODUCTION & OBJECTIVES: AlthoughBotulinum-AToxin(BTX-A)is knownto induce chemodenervation of both striated and smooth muscles, recent evidences in rat chemical cystitis model and in patientswith interstitial cystitissuggestthat the neurotoxinmay have an antinociceptive effect.Wesoughtto investigatethe effectsofBTX-Aonvisceralafferentnervetransmissionby measuring Nerve Growth Factor (NGF) bladder tissue concentrations in patients affected by neurogenic detrusor overaetivity before and after intravesical treatment with BTX-A. We also compared NGF bladder tissue content with clinical and urodynamicdata. MATERIAL & METHODS: Twenty-threespinal cord injured patients underwent urodynamics with the recording of uninhibited detmsor contractions (UDC) threshold, UDC maximumpressure, andmaximumcystometriccapacity,beforeandat 1and3monthsafterBTX-Ainjectionsintothe detrusor muscle. Endoscopicbladder wall biopsies were also taken at the same time points. NGF levels were measured in tissue homogenate by means of enzyme linked immunosorbent assay (ELISA,Promega,Madison-WI).Thesensitivitywas 15.6pg/mlofNGEDatawereexpressedas ng/mg protein (mean of duplicate samples). RESULTS: We detected a significant increase in UDC threshold (p<0.001) and in maximum cystometriccapacity(p<0.001),anda significantreductioninUDCmaximumpressure(p<0.001)at 1and3monthsaftertreatmenl ascomparedtobaseline.Furthermore,atthesametimepointswe detecteda significantreduction UDCthreshold(ml) UDC max pressure (emil20) Bladder capacity(ml) NGF(n~mg) ~<0.02)inNGFbladdertissuecontent(seeTablebelow). Baseline 165±92.2 62.3 i 21.8 246.3 ± 88.4 141.8 ± 73.1 1 month (mean± SD) 420± 105.6 17 4-20.7 437.9± 78.2 85.2±41 3 months (mean± SD) 445.5±52 [ 24.64- 32.5 ! 459.2 ± 64.7 78.7 :L39 p value (mean± SD) p< 0.001 p< 0.001 p< 0.001 p<0.02 CONCLUSIONS: These results demonstratethat BTX-Aintravesical administrationinduces a state ofNGF deprivationin bladdertissueofpatientswithneurogeniedetrusoroveractivity,probablyby interfering with NGF-dependent metabolism and/or production. This results in a decrease of hyperexcitability of C-fiber bladder afferents and, consequently, in the reduction of detrusor overactivity. Thus, BTX-A intravesical treatment may interact on both the afferent and efferent armsofthemicturitioureflex.