RESUMO
Interstitial cystitis (IC) is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. IC is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area, and diet can exacerbate IC symptoms. In this study, we used a murine neurogenic cystitis model to investigate the development of pelvic pain behavior. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis tail base muscle of female C57BL/6J mice. Infectious PRV virions were isolated only from the spinal cord, confirming the centrally mediated nature of this neurogenic cystitis model. Pelvic pain was assessed using von Frey filament stimulation to the pelvic region, and mice infected with PRV developed progressive pelvic pain. Pelvic pain was alleviated by 2% lidocaine instillation into either the bladder or the colon but not following lidocaine instillation into the uterus. The bladders of PRV-infected mice showed markers of inflammation and increased vascular permeability compared with controls. In contrast, colon histology was normal and vascular permeability was unchanged, suggesting that development of pelvic pain was due only to bladder inflammation. Bladder-induced pelvic pain was also exacerbated by colonic administration of a subthreshold dose of capsaicin. These data indicate organ cross talk in pelvic pain and modulation of pain responses by visceral inputs distinct from the inflamed site. Furthermore, these data suggest a mechanism by which dietary modification benefits pelvic pain symptoms.
Assuntos
Cistite Intersticial/fisiopatologia , Dor Pélvica/fisiopatologia , Anestésicos Locais/farmacologia , Animais , Comportamento Animal/fisiologia , Capsaicina/farmacologia , Colo/fisiologia , Cistite Intersticial/etiologia , Cistite Intersticial/patologia , Azul Evans , Feminino , Herpesvirus Suídeo 1 , Lidocaína/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Dor Pélvica/etiologia , Dor Pélvica/patologia , Estimulação Física , Pseudorraiva/complicações , Pseudorraiva/fisiopatologia , Ensaio de Placa ViralRESUMO
PURPOSE: To determine if bladder mast cell degranulation is involved in the genesis of neurogenic cystitis induced by pseudorabies virus (PRV) invasion of the central nervous system (CNS). MATERIALS AND METHODS: Rats received a total of 4 x 106 plaque forming units (pfu) of PRV-Bartha in the abductor caudalis dorsalis (ACD) muscle. Granulated bladder mast cells per mm2 of bladder tissue and urine histamine content were monitored as the cystitis developed over the next few days. In a subgroup of rats, intravesical resiniferatoxin was used to remove capsaicin-sensitive sensory bladder afferents, while another subgroup was pretreated with a mast cell degranulator. RESULTS: PRV injection into the ACD muscle leads to neurogenic cystitis. Histamine levels were elevated in the urine of virus injected rats before any behavioral or microscopical signs of cystitis were present. When the cystitis became clinically manifest, urine histamine returned to control levels, and the number of granulated mast cells dropped significantly. Rats in which capsaicin-sensitive afferents had been removed did not show any signs of cystitis, or increase in urine histamine, or change in the number of granulated mast cells. Pretreatment of animals with a mast cell degranulator completely prevented the appearance of cystitis without altering the CNS disease. CONCLUSION: These results provide further evidence that mast cells are involved in neurogenic cystitis induced by changes in CNS activity.
Assuntos
Degranulação Celular/fisiologia , Viroses do Sistema Nervoso Central/complicações , Cistite/virologia , Mastócitos/fisiologia , Inflamação Neurogênica/virologia , Pseudorraiva/complicações , Bexiga Urinária/patologia , Administração Intravesical , Análise de Variância , Animais , Capsaicina/farmacologia , Degranulação Celular/efeitos dos fármacos , Cistite/patologia , Cistite/urina , Denervação , Modelos Animais de Doenças , Diterpenos/administração & dosagem , Diterpenos/farmacologia , Histamina/urina , Masculino , Mastócitos/efeitos dos fármacos , Inflamação Neurogênica/patologia , Inflamação Neurogênica/urina , Neurônios Aferentes/efeitos dos fármacos , Neurotoxinas/administração & dosagem , Neurotoxinas/farmacologia , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervaçãoRESUMO
The purpose of the study was to evaluate the role which non-essential envelope glycoproteins play in the neuroinvasion and neural spread of ADV. The invasion and spread in the trigeminal nervous pathway with the Ka strain of ADV and its single deletion mutants Ka gI-, Ka gp63- and Ka gIII- were examined after intranasal inoculation in neonatal pigs by virus isolation and immunocytochemistry. Evaluation was performed in the nasal mucosa, trigeminal ganglion (1st neuronal level), ponsmedulla (2nd neuronal level) and thalamus-cerebellum (3rd neuronal level). The Ka gIII- mutant invaded up to the 3rd neuronal level of the trigeminal pathway and spread in a similar way to the parental Ka strain. The Ka gp63- mutant invaded up to the 3rd neuronal level but the spread of this mutant was impaired at all the neuronal levels. The Ka gI- mutant was least neuroinvasive and reached only up to the 2nd neuronal level. The results showed that glycoproteins gI and gp63 play a role in the invasion and spread of ADV in the nervous system. However, the gI glycoprotein appears to be the most important for neuroinvasion and neural spread of ADV in pigs. Therefore, gI deleted vaccines may be considered to be safer with respect to the neuroinvasion than vaccines carrying single deletions of other non-essential envelope glycoproteins.