Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis.
These studies examined changes in the expression of calcitonin gene-related peptide (CGRP) and substance P (SP) in lumbosacral (L6-S1) micturition reflex pathways, following chronic cystitis induced by cyclophosphamide (CYP). In control Wistar rats, CGRP- or SP-immunoreactivity (IR) was expressed in fibers in the superficial dorsal horn in all segmental levels examined (L4-S1). Bladder afferent cells in the dorsal root ganglia (DRG; L6, S1) from control animals also exhibited CGRP- (41-55%) or SP-IR (2-3%). Following chronic, CYP-induced cystitis, CGRP- and SP-IR were dramatically increased in spinal segments and DRG (L6, S1) involved in micturition reflexes. The density of CGRP- and SP-IR was increased in the superficial laminae (I-II) of the L6 and S1 spinal segments. No changes in CGRP- or SP-IR were observed in the L4-L5 segments. Staining was also dramatically increased in a fiber bundle extending ventrally from Lissauer's tract in lamina I along the lateral edge of the DH to the sacral parasympathetic nucleus in the L6-S1 spinal segments. Following chronic cystitis, CGRP- and SP-IR in cells in the L6 and S1 DRG significantly (P< or =0.05) increased and the percentage of bladder afferent cells expressing CGRP- (76%) or SP-IR (11-18%) also significantly (P< or =0.001) increased. No changes were observed in the L4-L5 DRG. These studies suggest that the neuropeptides, CGRP and SP, may play a role in urinary bladder afferent pathways, following chronic urinary bladder inflammation. Changes in CGRP or SP expression following cystitis may contribute to the altered visceral sensation (allodynia) and/or urinary bladder hyperreflexia in the clinical syndrome, interstitial cystitis.
Vizzard
M A
MA
Department of Anatomy and Neurology, University of Vermont College of Medicine, E219 Given Building, Burlington, VT 05405, USA. mvizzard@zoo.uvm.edu
D000344:Afferent Pathways / Q000166:cytology / Q000378:metabolism*; D000477:Alkylating Agents; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002908:Chronic Disease; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism; D009479:Neuropeptides / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000294:innervation*
D000477:Alkylating Agents; D009479:Neuropeptides; D003520:Cyclophosphamide; D015740:Calcitonin Gene-Related Peptide