HYPERREFLEXIA OF THE URINARY-BLADDER - POSSIBLE ROLE OF THE EFFERENT FUNCTION OF THE CAPSAICIN-SENSITIVE PRIMARY AFFERENTS

Purpose: Capsaicin sensitive primary efferents (CSPA) have been implic ated in the pathogenesis of hyperreflexia after spinalization. In this study we investigated the role of the efferent function of these fibe rs in detrusor hyperreflexia and its effect on detrusor physiology and pharmacology. Materials and Methods: Four groups of female Sprague Da wley rats were included in our study. These groups were normal control s, capsaicin treated normal rats, spinalized rats and capsaicin treate d spinalized rats. Six weeks following spinalization, animals were sub jected to cystometric study, and bladders were obtained for either in vitro detrusor contractility study or substance P (SP), neurokinin A ( NKA) and calcitonin gene related peptide (CGRP) quantification by radi oimmunoassay, Results: Spinalized animals consistently developed hyper reflexia after spinalization in the form of uninhibited contractions m ore than 15 cm. water in amplitude. This was accompanied by increased urinary bladder total content of the neuropeptides but without any cha nge in the detrusor contractility or neurokinin receptor pharmacology as shown by responses to KCI, electric field stimulation and neurokini n receptor selective agonists in the in vitro study. In the control gr oup, urinary bladder total content of SP, NKA and CGRP was 0.19 +/- 0. 03, 0.15 +/- 0.01 and 0.84 +/- 0.1 rho mol/bladder respectively. In co ntrast, in the spinalized animals, these were 0.44 +/- 0.07, 0.21 +/- 0.03 and 2.28 +/- 0.34 rho mol/bladder for the same peptides, respecti vely. Capsaicin treatment abolished hyperreflexia, which corresponded with the decrease in the neuropeptide content of the urinary bladder. The number and amplitude of the uninhibited contractions decreased dra matically. SP, NKA and CGRP reached 0.06 +/- 0.01, 0.07 +/- 0.01 and 0 .44 +/- 0.18 rho mol/bladder 2 weeks after capsaicin treatment in spin alized animals. This was associated with the occurrence of detrusor su per-sensitivity to both neurokinin receptor selective agonists. Conclu sion: This study demonstrates the importance of the efferent function of the CSPA in the pathogenesis of hyperreflexia. On the other hand, d etrusor changes were shown to be a non-crucial factor in the developme nt of hyperreflexia.