Functional, biochemical and anatomical changes in the rat urinary bladder induced by perigangliar injection of colchicine.
The aim of this study was to assess the effect of blocking the axonal transport of sensory neuropeptides, by local injection of colchicine at pelvic ganglia level, on the sensory and efferent functions mediated by capsaicin-sensitive primary afferent neurons innervating the rat urinary bladder. Bilateral injection of colchicine in the prostatic tissue underneath the pelvic ganglia of male rats induced a time-dependent reduction (maximal at 72 h, 100% reduction) of the in vitro contraction of the bladder strips induced by capsaicin (1 microM). The response to electrical field stimulation was also reduced, although to a lesser extent. The direct contractions induced by substance P (100 nM) or KCl (80 mM) were not affected by colchicine pretreatment. In vivo, perigangliar injection of colchicine (72 h before) greatly increased bladder 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 not the proximal ureter of colchicine-treated rats. Topical application of capsaicin onto the urinary bladder or onto the stomach induced a cardiovascular pressor reflex in urethane-anaesthetized, spinalized rats. Colchicine pretreatment reduced (by about 50%) the pressor response elicited by chemonociceptive stimulation of the bladder but not that arising 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 more intense staining of nerve fibres positive for calcitonin-gene related peptide-like immunoreactivity and tachykinin-like immunoreactivity was observed in pelvic ganglia of colchicine-pretreated rats. No changes were detected in the dorsal horns of spinal cord segments where pelvic bladder afferents project (L6-S1). Colchicine pretreatment reduced, but did not abolish, bladder levels of substance P-, neurokinin A-, calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity. However, vasoactive intestinal peptide-like immunoreactivity levels were not changed. The capsaicin-evoked (1 microM) release of calcitonin gene-related peptide was abolished in capsaicin as well as in colchicine-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 urinary bladder. Although reduced, tissue levels of sensory neuropeptides are not completely depleted, thus indicating the existence of a releasable versus non-releasable pool. The chemically induced blockade of axoplasmic transport also induces a limited impairment of the sensory function of capsaicin-sensitive afferents, and of the parasympathetic efferent system.
Lecci
A
A
Pharmacology Research Department, A. Menarini Pharmaceuticals, Florence, Italy.
Patacchini
R
R
De Giorgio
R
R
Corinaldesi
R
R
Theodorsson
E
E
Giuliani
S
S
Santicioli
P
P
Maggi
C A
CA
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D001370:Axonal Transport / Q000187:drug effects; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003078:Colchicine / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D005725:Ganglia, Autonomic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism
D009479:Neuropeptides; D002211:Capsaicin; D003078:Colchicine