Effects of phenazopyridine on rat bladder primary afferent activity, and comparison with lidocaine and acetaminophen

Aims: The clinical indication of phenazopyridine is unclear, it has been used clinically in conditions with increased bladder sensation as in cystitis and bladder pain syndrome/interstitial cystitis. We explored the effect of phenazopyridine on afferent nerve activity by direct measurement of both Aδ- and C-fibers in the rat, and compared the outcome with the effects of lidocaine (a local anesthetic) and of acetaminophen (an analgesic).

Methods: Female Sprague-Dawley rats were used. Under urethane anesthesia, single nerve fibers primarily originating from the bladder were identified in the L6 dorsal root by electrical stimulation of the left pelvic nerve and by bladder distention. By conduction velocity (2.5 m/sec) the fibers were defined as Aδ-fiber or C-fiber. The afferent activity in response to constant bladder filling was measured before the drug administration. Then, phenazopyridine (0.1-3 mg/kg) or lidocaine (0.3-3 mg/kg) or acetaminophen (1-10 mg/kg) was administrated intravenously. After drug administration, the afferent activity of bladder fillings was measured again.

Results: All drugs significantly increased bladder compliance, in a dose-dependent way. Twenty-eight single afferent fibers (Aδ-fibers: n = 13, C-fibers: n = 15) were isolated. Intravenous administration of phenazopyridine significantly decreased dose-dependently only the Aδ-fiber but not the C-fiber activity. Also acetaminophen significantly decreased only Aδ-fiber activity, but it was not dose-dependently completely. Lidocaine inhibited both the Aδ- and C-fiber activities.

Conclusions: This study shows that phenazopyridine can directly inhibit the mechanosensitive Aδ-fibers in the normal rat bladder. This finding might explain its clinical effect in conditions of bladder hypersensitivity.