Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis

Abstract

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≤0.05) increased and the percentage of bladder afferent cells expressing CGRP- (76%) or SP-IR (11–18%) also significantly ( P≤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.