Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity

ABSTRACT Objective: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. Materials and Methods: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. Results: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. Conclusions: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.

Comparative evaluation of somatosensory mechanisms involved in orofacial somatic, visceral and neuropathic pain / Avaliação comparativa dos mecanismos somatossensoriais envolvidos na gênese das dores orofaciais de origem somática, visceral e neuropática

Orofacial pain conditions can be classified into somatic, visceral or neuropathic pain. Somatic pain is triggered by a noxious stimulus generally inducted by peripheral traumas, such as dental implants surgeries (IMP). Visceral pain initiates within internal body tissues and is normally triggered by inflammation, as in inflammatory toothaches (IT). The third condition is neuropathic pain, which results from persistent injury to the peripheral nerve as in Atypical Odontalgia (AO). The aims of this study were: 1- to investigate somatosensory abnormalities, using mechanical, painful, and electrical quantitative sensory testing (QST), in somatic (IMP patients), visceral (IT) and neuropathic pain (AO); 2- to quantify how accurately QST discriminates an IT or AO diagnosis; and 3- to investigate the influence implant surgeries or pulpectomy may have on somatosensory system and sensory nerve fibers. Sixty subjects were divided in three groups: IMP (n = 20), IT (n = 20) and AO group (n = 20). A sequence of five QSTs and the Conditioned Pain Modulation Test (CPM) were performed one month and three months after dental implant surgery (IMP group) or pulpectomy (IT group). AO group was evaluated only at baseline. QST comprehended Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Dynamical Mechanical Allodynia (DMA), Current Perception Threshold (CPT) for A-beta (frequency of 2000Hz), A-delta (250Hz) and C fibers (5Hz) and Temporal Summation Test (TS). "Z" score transformation were applied to the data, and within and between groups were statistically analyzed using two-way ANOVA. In addition, the receiver operating characteristic curve analysis, diagnostic accuracy, sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of QSTs were calculated (α = 5%). The findings of this study proved that: 1- loss of function for touch threshold and electrical threshold of C fibers is present in inflammatory toothache; 2- allodynia, hyperalgesia, gain of function for touch and pain thresholds and impaired pain modulation is detected in atypical odontalgia; 3- some QSTs may be used as complementary tests in the differential diagnosis of atypical odontalgia and inflammatory toothache with strong accuracy; 4- the most accurate QSTs for differential diagnosis between subjects with AO and IT were MDT, MPT and DMA where touch threshold forces > 1 g/mm2 and pain threshold forces > 10g/mm2 can be used to accurately discriminate AO from IT; and 5- no somatosensory modification is found after implant surgery and reduced electrical threshold in C fiber is found for patients with inflammatory toothache after 3 months of pulpectomy.(AU)

As dores orofaciais podem ser classificadas em dores somáticas, viscerais ou neuropáticas. A dor somática está relacionada a um estímulo nocivo evidente, geralmente associada a um trauma periférico, como por exemplo, nas cirurgias de implantes (IMP). As dores viscerais têm origem dentro dos órgãos e cavidades internas do corpo e são ativadas pela inflamação, como no exemplo da dor de dente do tipo Pulpite Aguda (PA). A terceira condição é a dor neuropática, que resulta de uma lesão persistente ao nervo periférico, como ocorre na Odontalgia Atípica (OA). Os objetivos deste estudo foram: 1- avaliar as alterações somatossensoriais, por meio do uso de Testes Sensoriais Quantitativos (TSQ) mecânicos, dolorosos e elétricos em dores somáticas (pacientes IMP), viscerais (PA) e neuropáticas (OA); 2- quantificar a acurácia dos TSQs na descriminação diagnóstica de uma PA ou OA; e 3- investigar alterações somatossensoriais e nas fibras nervosas sensoriais após cirurgia de instalação de implantes dentários ou pulpectomia. Sessenta sujeitos foram divididos em três grupos: IMP (n = 20), PA (n = 20) e OA (n = 20). Uma sequência de cinco TSQs e o teste de Controle da Modulação da Dor (CMD) foram realizados um mês e três meses após cirurgia de implantes (grupo IMP) ou pulpectomia (grupo PA). No grupo OA, os testes foram realizados somente uma vez no início do estudo. Os TSQs englobaram o Limiar de Detecção Mecânica (LDM), Limiar de Dor Mecânica (LDoM), Alodinia Mecânica Dinâmica (AMD), Limiar de Percepção de Corrente (LPC) para fibras A-beta (frequência de 2000Hz), A-delta (250Hz) e C (5 Hz), e o teste de Somação Temporal (ST). A transformação em escores de "Z" foi aplicada aos dados, e diferenças intra e inter-grupos foram analisadas usando ANOVA de medidas repetidas. Ainda, a acurácia diagnóstica dos TSQs foi medida por meio da sensibilidade, especificidade, razão de verossimilhança e razão de chances para diagnóstico (α = 5%). Os resultados deste estudo mostraram que: 1- perda da função em limiar táctil e limiar elétrico de fibras C está presente na Pulpite Aguda; 2- alodinia, hiperalgesia, ganho de função nos limiares de tato e de dor, e modulação da dor prejudicada são encontrados em pacientes com odontalgia atípica; 3- alguns TSQs podem ser usados como testes diagnósticos complementares ao diagnóstico diferencial entre PA e OA; 4- os TSQs com maior acurácia para o diagnóstico diferencial entre indivíduos com PA e OA foram LDM LDoM e AMD, onde uma força maior que 1 g/mm2 para limiar de tato e maior que 10 g/mm2 para limiar de dor podem ser usados com precisão; e 5- nenhuma alteração somatossensorial é encontrada após cirurgia de implantes e uma redução no limiar elétrico em fibras C é encontrado em pacientes com PA após 3 meses da pulpectomia.(AU)

Effect of DA-9701 on Colorectal Distension-Induced Visceral Hypersensitivity in a Rat Model

BACKGROUND/AIMS: DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Corydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. METHODS: Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. RESULTS: In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. CONCLUSIONS: The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.