TY - JOUR
T1 - Impaired contraction and decreased detrusor innervation in a female rat model of pelvic neuropraxia
AU - Hannan, Johanna L.
AU - Powers, Shelby A.
AU - Wang, Vinson M.
AU - Castiglione, Fabio
AU - Hedlund, Petter
AU - Bivalacqua, Trinity J.
N1 - Funding Information:
This work was supported by the National Institutes of Health NIDDK K08 Career Development Award (TJB), Urology Care Foundation (JLH, TJB), and ECU startup funds (JLH). The authors would like to thank Xiaopu Liu and Elena Pak for their assistance in data collection.
Publisher Copyright:
© 2016, The International Urogynecological Association.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Introduction and hypothesis: Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI. Methods: Female Sprague–Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured. Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. Western blots measured M2 and M3 protein expression. Bladder sections were stained with Masson’s trichrome for SM content and immunofluorescence staining for nerve terminals expressing vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), and neuronal nitric oxide synthase (nNOS). Results: Bilateral pelvic nerve injury caused larger bladders with less SM content and increased collagen type 1α1 and 3α1 gene expression. At early time points, cholinergic-mediated contraction increased, whereas EFS-mediated contraction decreased and returned to baseline by 30 days. Protein and gene expression of M3 was decreased 3 and 7 days post-BPNI, whereas M2 was unchanged. TH nerve terminals surrounding the detrusor decreased in all BPNI groups, whereas VAChT and nNOS terminals decreased 14 and 30 days post-BPNI. Conclusions: Bilateral pelvic nerve injury increased bladder size, impaired contractility, and decreased SM and autonomic innervation. Therapeutic strategies preventing nerve injury-mediated decline in neuronal input and SM content may prevent the development of a neurogenic bladder and improve quality of life after invasive pelvic surgery.
AB - Introduction and hypothesis: Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI. Methods: Female Sprague–Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured. Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. Western blots measured M2 and M3 protein expression. Bladder sections were stained with Masson’s trichrome for SM content and immunofluorescence staining for nerve terminals expressing vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), and neuronal nitric oxide synthase (nNOS). Results: Bilateral pelvic nerve injury caused larger bladders with less SM content and increased collagen type 1α1 and 3α1 gene expression. At early time points, cholinergic-mediated contraction increased, whereas EFS-mediated contraction decreased and returned to baseline by 30 days. Protein and gene expression of M3 was decreased 3 and 7 days post-BPNI, whereas M2 was unchanged. TH nerve terminals surrounding the detrusor decreased in all BPNI groups, whereas VAChT and nNOS terminals decreased 14 and 30 days post-BPNI. Conclusions: Bilateral pelvic nerve injury increased bladder size, impaired contractility, and decreased SM and autonomic innervation. Therapeutic strategies preventing nerve injury-mediated decline in neuronal input and SM content may prevent the development of a neurogenic bladder and improve quality of life after invasive pelvic surgery.
KW - Autonomic innervation
KW - Detrusor
KW - Neurogenic bladder
KW - Neuropraxia
KW - Radical hysterectomy
UR - http://www.scopus.com/inward/record.url?scp=85006364705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006364705&partnerID=8YFLogxK
U2 - 10.1007/s00192-016-3223-1
DO - 10.1007/s00192-016-3223-1
M3 - Article
C2 - 27987021
AN - SCOPUS:85006364705
VL - 28
SP - 1049
EP - 1056
JO - International Urogynecology Journal and Pelvic Floor Dysfunction
JF - International Urogynecology Journal and Pelvic Floor Dysfunction
SN - 0937-3462
IS - 7
ER -