Afferent Mechanisms of Pelvic Hypersensitivity

盆腔过敏的传入机制

• 批准号: 8531919
• 负责人: Gerald F Gebhart
• 金额: $ 56.5万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531919
• 关键词: Address; Area; Attenuated; Behavioral; Bladder; CNS processing; Chronic; Colorectal; Cutaneous; Development; Disease; Electric Stimulation; Exhibits; Feces; Frequencies; Functional disorder; Gastroenterologist; Gynecologist; Habits; Hyperalgesia; Hypersensitivity; Inflammation; Inflammatory; Interstitial Cystitis; Intestines; Irritable Bowel Syndrome; Local Anesthetics; Local anesthesia; Maintenance; Mus; Nerve; Neurons; Nociceptors; Organ; Pain; Pain Disorder; Pathology; Pathway interactions; Patients; Pelvic Pain; Pelvis; Persons; Process; Rectal Administration; Recurrence; Relative (related person); Research; Role; Signs and Symptoms; Spinal Ganglia; Stimulus; Stretching; Symptoms; Time; Tissues; Urologist; Visceral; Visceral Afferents; Visceral pain; Woman; chronic abdominal pain; chronic pain; intravesical; nerve supply; rectal; research study; response

DESCRIPTION (provided by applicant): Persons with chronic abdominal and pelvic pain disorders comprise a large proportion of patients seeking relief from gastroenterologists, urologists and gynecologists. Two common pelvic disorders, painful bladder syndrome (PBS) and irritable bowel syndrome (IBS), are characterized by altered bladder/bowel habits (e.g., urge, frequency and, in IBS, stool consistency), pain and hypersensitivity. These patients typically exhibit significantly lower response thresholds to provocative stimuli (e.g., cystometry, rectal distension), complain of increased sensitivity during normal organ function, and exhibit increased tenderness in areas of somatic referral which, in addition, are expanded in size. Interestingly, PBS and IBS exist in the absence of an apparent pathobiological cause and are thus characterized as 'functional.' It is widely assumed that functional disorders reflect altered CNS processing, but considerable evidence suggests that persistent afferent drive contributes significantly to the recurrent, unexplained pain and hypersensitivity that characterize them. The objective of this proposal is to determine the mechanisms by which pain and hypersensitivity arise and is maintained as a necessary step in developing better informed and more successful management strategies. The Aims include: 7 Aim 1: characterize the proportions of mechano-sensitive and insensitive afferents in electrophysiological experiments in the both the lumbar splanchnic and pelvic nerve innervations of the bladder and colorectum. 7 Aim 2: evaluate organ hypersensitivity in behavioral experiments, after which the proportions of bladder and colorectal mechanically insensitive afferents (MIAs) will be determined in bladder and colorectum removed from hypersensitive mice. We hypothesize the proportions of MIAs will be significantly reduced in organs from hypersensitive mice relative to normal controls. 7 Aim 3: identify the 'chemotypes' of mechano-sensitive and insensitive bladder and colorectal dorsal root ganglion neurons in both the lumbar splanchnic and pelvic nerve pathways. We hypothesize that there are significant differences in chemotype between MIAs and mechanosensitive afferents as well as between different mechanosensitive afferents and, further, between organs.

描述（由申请人提供）：患有慢性腹部和骨盆疼痛障碍的人占很大一部分患者，寻求胃肠病医生，泌尿科医生和妇科医生的救济。两种常见的骨盆疾病，疼痛的膀胱综合征（PBS）和肠易激综合征（IBS）的特征是改变了膀胱/肠子/肠习惯（例如，急症，频率，频率，IBS，粪便一致性），疼痛和高敏性。这些患者通常表现出对挑衅性刺激的反应阈值的明显较低（例如囊肿，直肠扩张），抱怨在正常器官功能期间提高敏感性，并且在体细胞转介的区域中表现出较高的压痛，此外，这些敏感性也会增加。有趣的是，PBS和IB存在于没有明显病理学原因的情况下，因此被认为是“功能”。人们普遍认为功能障碍反映了CNS处理的改变，但是大量证据表明，持续的传入驱动驱动力对它们的复发性，无法解释的疼痛和超敏反应的表征显着贡献。该提案的目的是确定疼痛和超敏反应的机制，并将其作为制定更好知情和更成功的管理策略的必要步骤。目的包括：7 AIM 1：表征在腰椎膜和膀胱和结肠菌的腰神经和骨盆神经神经上的电生理实验中机械敏感和不敏感传入的比例。 7 AIM 2：在行为实验中评估器官的超敏反应，然后将在膀胱和结肠敏感的传入（MIA）中的比例在膀胱中确定从高敏小鼠中取出的膀胱和结肠菌。我们假设相对于正常对照组，高敏小鼠的器官中，MIA的比例将显着降低。 7 AIM 3：确定腰膜和骨盆神经途径中的机械敏感性和不敏感膀胱和结直肠根神经元神经元的“化学型”。我们假设MIA和机械敏感传入之间以及不同机械敏感的传入与器官之间的化学型之间存在显着差异。