A. Lecci et al., FUNCTIONAL, BIOCHEMICAL AND ANATOMICAL CHANGES IN THE RAT URINARY-BLADDER INDUCED BY PERIGANGLIAR INJECTION OF COLCHICINE, Neuroscience, 71(1), 1996, pp. 285-296
The aim of this study was to assess the effect of blocking the axonal
transport of sensory neuropeptides, by local injection of colchicine a
t pelvic ganglia level, on the sensory and efferent functions mediated
by capsaicin-sensitive primary afferent neurons innervating the rat u
rinary bladder. Bilateral injection of colchicine in the prostatic tis
sue underneath the pelvic ganglia of male rats induced a time-dependen
t reduction (maximal at 72 h, 100% reduction) of the in vitro contract
ion of the bladder strips induced by capsaicin (1 mu M). The response
to electrical field stimulation was also reduced, although to a lesser
extent. The direct contractions induced by substance P (100 nM) or KC
l (80 mM) were not affected by colchicine pretreatment. In vivo, perig
angliar injection of colchicine (72 h before) greatly increased bladde
r capacity, and reduced the amplitude of micturition contractions and
micturition frequency. Capsaicin-induced plasma protein extravasation
was abolished in the urinary bladder and reduced in the distal, but no
t the proximal ureter of colchicine-treated rats. Topical application
of capsaicin onto the urinary bladder or onto the stomach induced a ca
rdiovascular presser reflex in urethane-anaesthetized, spinalized rats
. Colchicine pretreatment reduced (by about 50%) the presser response
elicited by chemonociceptive stimulation of the bladder but not that a
rising from the stomach. Colchicine pretreatment did not produce overt
changes of nerve profiles immunoreactive for calcitonin gene-related
peptide- or tachykinin-like material in the rat urinary bladder. A mor
e intense staining of nerve fibres positive for calcitonin-gene relate
d peptide-like immunoreactivity and tachykinin-like immunoreactivity w
as observed in pelvic ganglia of colchicine pretreated rats. No change
s were detected in the dorsal horns of spinal cord segments where pelv
ic bladder afferents project (L(6)-S-1). Colchicine pretreatment reduc
ed, but did not abolish, bladder levels of substance P-, neurokinin A-
, calcitonin gene-related peptide- and neuropeptide Y-like immunoreact
ivity. However, vasoactive intestinal peptidelike immunoreactivity lev
els were not changed. The capsaicin-evoked (1 mu M) release of calcito
nin gene-related peptide was abolished in capsaicin as well as in colc
hicine-pretreated animals. The present findings demonstrate that local
treatment of pelvic ganglia with colchicine totally eliminates the ''
efferent'' functions of capsaicin-sensitive afferent nerves in the uri
nary bladder. Although reduced, tissue levels of sensory neuropeptides
are not completely depleted, thus indicating the existence of a relea
sable versus non-releasable pool. The chemically induced blockade of a
xoplasmic transport also induces a limited impairment of the sensory f
unction of capsaicin-sensitive afferents, and of the parasympathetic e
fferent system.