Diagram showing possible C-fiber primary afferent pathways controlling bladder reflexes in the spinal cord injured cat and their modulation by activation of muscarinic, nicotinic, and serotonergic receptors. 1. Population of afferents responsible for eliciting pre-micturition contractions. 2. Population of afferents responsible for eliciting micturition contractions. Primary afferents synapse with spinal excitatory interneurons (white) which have excitatory synaptic connections with a parasympathetic preganglionic neuron (shaded) which in turn projects to a peripheral parasympathetic ganglion. Note that OXO-M stimulates both types of afferents either by directly activating muscarinic receptors (▬) on the afferent nerves or indirectly by activating muscarinic receptors (▬) on urothelial cells which in turn release urothelial cell transmitters (UCT) that stimulate afferent nerves. Nicotine reduces BC without affecting PMC activity by directly stimulating nicotinic receptors (□) on type 2 afferent nerves or stimulating receptors (□) on the urothelial cells which in turn release urothelial cell transmitters (UCT) that stimulate type 2 afferent nerves to reduce BC without affecting PMC activity. 8-OH-DPAT selectively targets spinal interneuronal circuitry (white neuron) activated by type 2 afferents to suppress type 2 afferent input to the preganglionic neuron and thereby suppresses the OXO-M-induced reduction in BC without affecting the OXO-M-induced changes in PMC activity. UT = urothelium, LP = lamina propria, SM = smooth muscle, MR = muscarinic receptor, NR = nicotinic receptor, UCT = urothelial cell transmitter.