Afferent Mechanisms of Pelvic Hypersensitivity

盆腔过敏的传入机制

• 批准号: 8335201
• 负责人: Gerald F Gebhart
• 金额: $ 58.13万
• 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/8335201
• 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; 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; painful bladder syndrome; 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）：在向胃肠病学家、泌尿科医生和妇科医生寻求缓解的患者中，很大一部分患有慢性腹部和盆腔疼痛疾病。两种常见的盆腔疾病，膀胱疼痛综合征 (PBS) 和肠易激综合征 (IBS)，其特征是膀胱/肠道习惯改变（例如，急迫感、频率，以及 IBS 中的大便稠度）、疼痛和过敏。这些患者通常对刺激刺激（例如膀胱测压、直肠扩张）表现出明显较低的反应阈值，抱怨在正常器官功能期间敏感性增加，并且在躯体转诊区域表现出压痛增加，此外，尺寸扩大。有趣的是，PBS 和 IBS 在没有明显病理原因的情况下存在，因此具有“功能性”特征。人们普遍认为功能障碍反映了中枢神经系统处理的改变，但大量证据表明，持续的传入驱动在很大程度上导致了复发性、无法解释的疼痛和过敏症的特征。该提案的目的是确定疼痛和过敏症产生和维持的机制，作为制定更明智和更成功的管理策略的必要步骤。目标包括： 7 目标 1：表征膀胱和结直肠的腰内脏和骨盆神经神经支配的电生理学实验中机械敏感和不敏感传入的比例。 7 目标 2：在行为实验中评估器官过敏，然后从过敏小鼠身上取出膀胱和结直肠，测定膀胱和结直肠机械不敏感传入神经 (MIA) 的比例。我们假设，与正常对照相比，过敏小鼠器官中 MIA 的比例将显着减少。 7 目标 3：识别腰内脏和骨盆神经通路中机械敏感和不敏感的膀胱和结直肠背根神经节神经元的“化学型”。我们假设 MIA 和机械敏感传入神经之间、不同机械敏感传入神经之间以及器官之间的化学型存在显着差异。