The pathophysiology of the overactive bladder associated with spinal cord injury : Involvement of capsaicin-sensitive primary bladder afferent nerves

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(1) In conscious rats with and without cronic spinal cord injury (SCI), the effect of intravesical instillation of capsaicin or resiniferatoxin (RTX) on volume-induced rhythmic bladder contractions (RBCs). Both capsaicin (0.1 and 1 mM) and RTX (1 and 10 μM ), instilly intravesically, were found to inhibit RBCs in both control and SCI rats. There was no qualitative difference in response to the drugs between the two groups. However, RTX was approximately 100 times more potent than capsaicin^2.(2) The clinical and urodynamic effects of intravesical instillation of capsaicin (2 mM in 5 patients) or RTX (1 μM in 3 patients) were investigated in 8 patients with overactive bladder associated with chronic spinal cord injury. Both of these two drugs surppress the overactive bladder and improved both reflexic urinary incontinence and symptoms related to autonomic dysreflexia. The beneficial effect emerged more quickly after RTX treatment than after capsaicin, and lasted for at least 3 months after either of the two drugs. No adverse effects was found.(3) The relaxant response to adrenergic stimulation in the human normal detrusor was found to be mediated mainly through β3-adrenoceptors (β3-ARs)^1. This was true also in neurogenic (both hyper-reflexic and low-compliant) bladders ^3, ^<12>. Selective β3-AR agonists induced bladder relaxation without affecting the cardiovascular system in the ferret ^7 and surppressed bladder overactivity induced by intravesical instillation of prostaglandin E2 in conscious rats ^5 and bladder overactivity in cerebral infarcted rats^4. These results suggest that selective β3-AR agonists may be used for the treatment of overactive bladder.(4) Cystometric study in conscios rats showed that Dopamine D1 receptors tonically inhibit the micturition reflex and D2 receptors are involved in facilitation of the micturition reflex^<13>.