X Pang1, J Marchand, G R Sant, R M Kream, T C Theoharides. 1. Department of Pharmacology and experimental Therapeutics, Tufts University School of Medicine, New England Medical Center Hospitals, Boston, USA.
Abstract
OBJECTIVE: To explore the presence of the neuropeptide substance P (SP) in the bladders of rats and humans and to investigate its relationship to mast cells (MCs) in interstitial cystitis (IC), a bladder disorder which occurs mostly in women and is characterized by frequency of voiding, nocturia and debilitating suprapubic pain. PATIENTS, MATERIALS AND METHODS: Bladder biopsies from eight women with untreated IC (mean age 36 years, range 29-58) and five control patients with no IC were analysed and compared with each other and with bladder tissue from 12 rats. Immunohistochemistry and image analysis were used to examine the density of SP-positive nerve fibres and their relationship with MCs. RESULTS: SP-containing nerve fibres were present in the bladder of both rats and humans. They were increased only in the submucosa, but not in the detrusor, of IC patients and were frequently seen in juxtaposition to MCs. CONCLUSION: SP, a neuropeptide secreted from sensory nerve endings, has been implicated in the pathophysiology of pain and has been shown to trigger MC secretion. Moreover, MC secretion by SP is augmented by oestradiol and bladder MCs have been shown to express high affinity oestrogen receptors. A functional relationship between SP and MCs may explain the pathophysiology of the neuro-inflammatory and painful nature of IC.
OBJECTIVE: To explore the presence of the neuropeptide substance P (SP) in the bladders of rats and humans and to investigate its relationship to mast cells (MCs) in interstitial cystitis (IC), a bladder disorder which occurs mostly in women and is characterized by frequency of voiding, nocturia and debilitating suprapubic pain. PATIENTS, MATERIALS AND METHODS: Bladder biopsies from eight women with untreated IC (mean age 36 years, range 29-58) and five control patients with no IC were analysed and compared with each other and with bladder tissue from 12 rats. Immunohistochemistry and image analysis were used to examine the density of SP-positive nerve fibres and their relationship with MCs. RESULTS:SP-containing nerve fibres were present in the bladder of both rats and humans. They were increased only in the submucosa, but not in the detrusor, of IC patients and were frequently seen in juxtaposition to MCs. CONCLUSION:SP, a neuropeptide secreted from sensory nerve endings, has been implicated in the pathophysiology of pain and has been shown to trigger MC secretion. Moreover, MC secretion by SP is augmented by oestradiol and bladder MCs have been shown to express high affinity oestrogen receptors. A functional relationship between SP and MCs may explain the pathophysiology of the neuro-inflammatory and painful nature of IC.