Activation for CNS Circuits Producing a Neurogenic Cystitis: Evidence for Centrally Induced Peripheral Inflammation

Abstract

We present a model of neurogenic cystitis induced by viral infection of specific neuronal circuits of the rat CNS. Retrograde infection by pseudorabies 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 themselves or of circuits distant from these rarely produced cystitis. Absence 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 integrity of central bladder-related circuits is necessary for the appearance of bladder inflammation, because only CNS lesions affecting bladder circuits, i.e., bilateral dorsolateral or ventrolateral funiculectomy, as well as bilateral lesions of Barrington's nucleus/locus coeruleus area, prevented bladder inflammation. The close proximity in the CNS of noninfected visceral circuits to infected somatic neurons would thus permit a bystander effect, leading to activation of the sensory and autonomic circuits innervating the bladder and resulting in a neurogenic inflammation localized to the bladder. The present study indicates that CNS dysfunction can bring about a peripheral inflammation.

Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization

“…Similarly, at lower intravesical pressures (10 -20 mmHg), the TNBSinduced sensitization of bladder afferents (as manifested by lowered sensory thresholds) was ameliorated following denervation as were changes in basal afferent activity. Although pelvic organ denervation was not performed in our previous studies of pelvic organ cross-sensitization (34), neurogenic cystitis induced in the central nervous system by the pseudorabies virus was similarly preventable by bladder denervation, again implicating neural pathways (22).…”

Vulvodynia: New Thoughts on a Devastating Condition

“…For example, experimentally induced inflammation of the colon or uterus produces inflammation not only in the intentionally targeted organ but also in the bladder and the skin and animals with endometriosis have reduced bladder capacity, vaginal hyperalgesia, and increased visceral pain (28)(29)(30)(31)(32). This process requires intact CNS connections and is mediated by neurogenic inflammation; visceral and somatic pathology can be induced by inflammatory CNS lesions alone, and both referred pain and pathology can be prevented by surgically interrupting the neural connections (26,29,(30)(31)(32)(33).…”

“…The phenomenon of convergence explains the higher incidence of other pelvic pain syndromes in women with vulvar dysesthesia, such as high-tone pelvic floor dysfunction, irritable bowel syndrome, and interstitial cystitis (33)(34)(35)(36). Pelvic floor tone is normal in asymptomatic women, but is increased in 10% to 100% of women with vulvar pain (15,(35)(36)(37)(38)(39).…”

Nerve growth factor release from the urothelium increases via activation of bladder C‐fiber in rats with cerebral infarction

“…In fact, it has been demonstrated that infection of the central nervous system can produce neurogenic inflammation in the bladder via activation of central bladder circuits. 19 These effects were prevented by total denervation of the bladder or selective C-fiber deafferentation without affecting the central nervous system. 19 NGF is released after inflammatory damage and contributes to the swift modification of the pain and micturition threshold, leading to hyperalgesia and DO.…”