ACTIVATION OF CNS CIRCUITS PRODUCING A NEUROGENIC CYSTITIS - EVIDENCEFOR CENTRALLY INDUCED PERIPHERAL INFLAMMATION

We present a model of neurogenic cystitis induced by viral infection o f specific neuronal circuits of the rat CNS. Retrograde infection by p seudorabies virus (PRV) of neuronal populations neighboring those that innervate the bladder consistently led to a localized immune response in the CNS and bladder inflammation. Infection of bladder circuits th emselves or of circuits distant from these rarely produced cystitis. A bsence of virus in bladder and urine ruled out an infectious cystitis. Total denervation of the bladder, selective C-fiber deafferentation, or bladder sympathectomy prevented cystitis without affecting the CNS disease, indicating a neurogenic component to the inflammation. The in tegrity of central bladder-related circuits is necessary for the appea rance of bladder inflammation, because only CNS lesions affecting blad der circuits, i.e., bilateral dorsolateral or ventrolateral funiculect omy, as well as bilateral lesions of Barrington's nucleus/locus coerul eus area, prevented bladder inflammation. The close proximity in the C NS of noninfected visceral circuits to infected somatic neurons would thus permit a bystander effect, leading to activation of the sensory a nd autonomic circuits innervating the bladder and resulting in a neuro genic inflammation localized to the bladder. The present study indicat es that CNS dysfunction can bring about a peripheral inflammation.