The most common cause of bladder dysfunction in males is obstruction due to benign prostatic hypertrophy. During the course of obstruction there is hypertrophy of the smooth muscle, and, in many cases, the bladder becomes hyperactive (238). In the rat, partial urethral ligation results in muscle hypertrophy (239), enhanced spinal micturition reflexes, and increased frequency of voiding (240). Following hypertrophy, there is an increase in the size of autonomic postganglionic neurons in the major pelvic ganglion of the rat (239,241,242). Neural input is not a prerequisite for neuronal growth since it still occurs in obstruction when the major pelvic ganglion has been decentralized or following destruction of unmyelinated sensory nerves by capsaicin.
Receptor expression may also be affected following obstruction. Increased expression of a-adrenoceptors has been observed in human bladder strips from patients with prostatic bladder obstruction and NA can cause contraction of the muscle, a response that does not usually occur in unobstructed bladder (243). Similarly, under normal conditions, the contractile response to nerve stimulation in human bladder does not contain a significant purinergic component indicated by atropine resistance. However, increased purinergic transmission can be demonstrated in patients with unstable obstructed bladders (244,245; see also Ref. 246). Upregulation of purinergic receptors appears to occur in hyperreflexia whether this is due to obstruction (244,245), interstitial cystitis (247), or neurogenic bladders (248).
DRG neurons with projections to the bladder also increase in size in bladder hypertrophy of the rat. In addition, there is increased expression of a growth associated protein (GAP-43) in afferent projections to the spinal cord including regions surrounding the parasympathetic nucleus (240). NGF levels are significantly increased in obstruction-induced hypertrophy of the bladder in rats (238,242). Furthermore, autoimmunity to NGF can prevent the increase in size of both major pelvic ganglion neurons and dorsal root ganglion neurons induced by obstruction (240,242). Autoimmunity to NGF also abolishes increased GAP-43 expression and can eliminate enhancement of the micturition reflex in obstruction (240).
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