Hyperreflexia of the urinary bladder: possible role of the efferent function of the capsaicin sensitive primary afferents.
OBJECTIVE
Capsaicin sensitive primary afferents (CSPA) have been implicated in the pathogenesis of hyperreflexia after spinalization. In this study we investigated the role of the efferent function of these fibers in detrusor hyperreflexia and its effect on detrusor physiology and pharmacology.


METHODS
Four groups of female Sprague Dawley rats were included in our study. These groups were normal controls, capsaicin treated normal rats, spinalized rats and capsaicin treated spinalized rats. Six weeks following spinalization, animals were subjected 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 radioimmunoassay.


RESULTS
Spinalized animals consistently developed hyperreflexia after spinalization in the form of uninhibited contractions more than 15 cm. water in amplitude. This was accompanied by increased urinary bladder total content of the neuropeptides but without any change in the detrusor contractility or neurokinin receptor pharmacology as shown by responses to KCl, electric field stimulation and neurokinin receptor selective agonists in the in vitro study. In the control group, urinary bladder total content of SP, NKA and CGRP was 0.19+/-0.03, 0.15+/-0.01 and 0.84+/-0.1 pmol/bladder respectively. In contrast, in the spinalized animals, these were 0.44+/-0.07, 0.21+/-0.03 and 2.28+/-0.34 pmol/bladder for the same peptides, respectively. 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 dramatically. SP, NKA and CGRP reached 0.06+/-0.01, 0.07+/-0.01 and 0.44+/-0.18 pmol/bladder 2 weeks after capsaicin treatment in spinalized animals. This was associated with the occurrence of detrusor super-sensitivity to both neurokinin receptor selective agonists.


CONCLUSIONS
This study demonstrates the importance of the efferent function of the CSPA in the pathogenesis of hyperreflexia. On the other hand, detrusor changes were shown to be a noncrucial factor in the development of hyperreflexia.
Shaker
H S
HS
Urology Research Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Tu
L M
LM
Kalfopoulos
M
M
Hassouna
M
M
Dion
S
S
Elhilali
M
M
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012021:Reflex, Abnormal / Q000502:physiology*; D001743:Urinary Bladder / Q000737:chemistry / Q000503:physiopathology*
D009479:Neuropeptides; D002211:Capsaicin