The role of DAMPS in painful bladder syndrome

描述(申请人提供)：膀胱痛综合征(BPS或间质性膀胱炎，IC)患者通常表现出明显的盆底肌肉压痛，仅针对这些肌肉的治疗通常会导致膀胱症状的显著改善。这种病因不明的衰弱综合征通常被假设为与微生物感染有关，但尚未得到证实。为了更好地了解BPS/IC的机制，我们将研究一个动物模型，在该模型中，盆底肌肉单独损伤(躯体损伤)是指损伤相关分子模式(DAMP)通过识别病原体相关分子模式(PAMPs)的神经元受体发出信号的程度。在这种损伤模型中观察到的行为变化的一个潜在的神经生物学机制是膀胱相关感觉神经节中存在的伤害性信号的增加。为此，在啮齿类动物身上验证我们的损伤模式作为BPS/IC的实验代表，为我们提供了一些参数来测试躯体和内脏高敏感性的潜在媒介。此外，这些拟议实验的结果也可能提供潜在的治疗靶点。总之，临床相关动物模型的使用将为我们提供独特的机会来改进PBS/IC诊断和治疗范例，并增加对女性慢性盆腔疼痛状况发生和维持的潜在机制的理解。

DESCRIPTION (provided by applicant): Bladder pain syndrome (BPS or interstitial cystitis, IC) patients typically exhibit marked tenderness of pelvic floor musculature and that treatments directed solely at those muscles often resulted in marked improvement of bladder symptoms. This debilitating syndrome of unknown etiology is often postulated, but not proven, to be associated with microbial infection. To better understand the mechanisms that contribute to BPS/IC, we will study an animal model in which pelvic floor muscle injury alone (somatic injury) the degree to which damage- associated molecular patterns (DAMPs) signal through neuronal receptors that recognize pathogen-associated molecular patterns (PAMPs). A potential neurobiological mechanism for the behavioral changes observed with this injury model is the increased nociceptive signaling present in bladder-associated sensory ganglia. To this end, validation of our injury paradigm in the rodent as an experimental representation of BPS/IC provides us with a number of parameters with which to test potential mediators of somatic and visceral hypersensitivity. Furthermore, the outcomes of these proposed experiments may also provide potential therapeutic targets. Taken together, the use of a clinically-relevant animal model will provide us with the unique opportunity to improve PBS/IC diagnostic and treatment paradigms and increase the understanding of the mechanisms underlying the development and maintenance of chronic pelvic pain conditions in women.