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 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.