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Expression of Inflammatory Mediators in Sensory Ganglia Innervating Lower Urinary Tract And Dysfunctional Voiding

Login to Access Video or Poster Abstract: MP11-06
Sources of Funding: NIDDK, U54 DK112079

Introduction

Dysfunctional voiding associated with chronic prostatic inflammation _x000D_ is considered to be caused by sensitization of primary sensory neurons innervating lower urinary tract. Published research implicates pro-inflammatory cytokines as major player in the neural sensitization and the progression of prostatitis. Therefore, we investigated the expression of cytokines and chemokines in dorsal root ganglia (DRG) from the lumbosacral region in rat model of non-bacterial prostatitis.

Methods

Intraprostatic injection of formalin (50μL) or saline (sham) was performed in three month- old male Sprague-Dawley rats to induce prostatitis(n=3). 12 hour night time urination pattern were noted a day before injection and 7 days later. Lumbosacral L6-S1 and cervical (C4) DRG were isolated from the sacrificed animals on the 7th day for multiplex analysis of 27 cytokines, chemokines and growth factors using a MILLIPLEX MAP Rat Cytokine/Chemokine Panel kit. Results are expressed as pg/mg of total protein

Results

The expression of IFN-γ, CXCL-10, VEGF and EGF was signficantly elevated in the L6-S1 DRG relative to the C4 DRG of either group(*p<0.05). Expression of CXC chemokines (CXCL-1, CXCL-2, CXCL-5), CC chemokines (CCL2, CCL3, CCL5), leptin, IL-2, IL-13 and IL-17A was only elevated in L6-S1 DRG relative to C4 DRG of sham group (#p<0.05). Frequent urination and reduced voided volume in the prostatitis group was also associated with substantial but insignficant increase in the production of CXCL-1 (p=0.06), CCL2 and leptin in the C4 DRG relative to that of the sham group. _x000D_

Conclusions

Dysfunctional voiding secondary to prostatic inflammation was linked to the dramatic overproduction of inflammatory mediators in L6-S1 DRG capable of inducing phenotypic changes in micturition reflex pathways. Since cervical DRG is not directly innervated by the axons of afferent neurons from prostate and bladder, therefore, sustantial production of leptin, CXCL-1 and CCL2 in the cervical DRG may be humorally mediated in prostatitis to suggest a role for neurohumoral interaction in the evolution of prostatitis into a regional pain syndrome.

Funding

NIDDK, U54 DK112079

Authors
Pradeep Tyagi
Mahendra Kashyap
Zhou Wang
Naoki Yoshimura
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