Int Neurourol J.  2017 Sep;21(3):178-188. 10.5213/inj.1734984.492.

Afferent Pathway-Mediated Effect of α1 Adrenergic Antagonist, Tamsulosin, on the Neurogenic Bladder After Spinal Cord Injury

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Kyung Hee Medical Center, College of Medicine, Kyung Hee University, Seoul, Korea.
  • 2Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
  • 3Department of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 4Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • 5Department of Urology, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Korea. kimcho99@gilhospital.com

Abstract

PURPOSE
The functions of the lower urinary tract (LUT), such as voiding and storing urine, are dependent on complex central neural networks located in the brain, spinal cord, and peripheral ganglia. Thus, the functions of the LUT are susceptible to various neurologic disorders including spinal cord injury (SCI). SCI at the cervical or thoracic levels disrupts voluntary control of voiding and the normal reflex pathways coordinating bladder and sphincter functions. In this context, it is noteworthy that α1-adrenoceptor blockers have been reported to relieve voiding symptoms and storage symptoms in elderly men with benign prostatic hyperplasia (BPH). Tamsulosin, an α1-adrenoceptor blocker, is also considered the most effective regimen for patients with LUT symptoms such as BPH and overactive bladder (OAB).
METHODS
In the present study, the effects of tamsulosin on the expression of c-Fos, nerve growth factor (NGF), and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the afferent micturition areas, including the pontine micturition center (PMC), the ventrolateral periaqueductal gray matter (vlPAG), and the spinal cord (L5), of rats with an SCI were investigated.
RESULTS
SCI was found to remarkably upregulate the expression of c-Fos, NGF, and NADPH-d in the afferent pathway of micturition, the dorsal horn of L5, the vlPAG, and the PMC, resulting in the symptoms of OAB. In contrast, tamsulosin treatment significantly suppressed these neural activities and the production of nitric oxide in the afferent pathways of micturition, and consequently, attenuated the symptoms of OAB.
CONCLUSIONS
Based on these results, tamsulosin, an α1-adrenoceptor antagonist, could be used to attenuate bladder dysfunction following SCI. However, further studies are needed to elucidate the exact mechanism and effects of tamsulosin on the afferent pathways of micturition.

Keyword

Spinal cord injury; Tamsulosin; c-Fos; Nerve growth factor; Nitric oxide synthase

MeSH Terms

Adrenergic Antagonists*
Afferent Pathways
Aged
Animals
Brain
Ganglia
Humans
Male
NAD
Nerve Growth Factor
Nervous System Diseases
Nitric Oxide
Nitric Oxide Synthase
Periaqueductal Gray
Prostatic Hyperplasia
Rats
Reflex
Spinal Cord Dorsal Horn
Spinal Cord Injuries*
Spinal Cord*
Urinary Bladder
Urinary Bladder, Neurogenic*
Urinary Bladder, Overactive
Urinary Tract
Urination
Adrenergic Antagonists
NAD
Nerve Growth Factor
Nitric Oxide
Nitric Oxide Synthase
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