Sex Differences in Stress Exacerbated Orofacial Pain in a Rat Model of Temporomandibular Joint Disorder

颞下颌关节紊乱病大鼠模型中压力的性别差异加剧口面部疼痛

• 批准号: 10693885
• 负责人: Daisy Jacqueline Cantu
• 金额: $ 0.92万
• 依托单位: TEXAS WOMAN'S UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-10-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10693885
• 关键词: Affective; Afferent Neurons; Animal Model; Animals; Anterior; Baltimore; Basic Science; Behavioral Assay; Biology; Cells; Chronic stress; Clinical Research; Confocal Microscopy; Craniofacial Pain; Cross Bite; Data; Dentistry; Detection; Doctor of Philosophy; Estrogen Replacements; Experimental Designs; Exposure to; Female; Flow Cytometry; Gene Expression; Genes; Goals; Gonadal Hormones; Immunohistochemistry; Inflammation; Inflammatory; Knowledge; Maryland; Masseter Muscle; Mentorship; Methods; Microglia; Modeling; Modernization; Neurobiology; Neuroglia; Neuronal Plasticity; Neurons; Orofacial Pain; Pain; Pain management; Pathway interactions; Patients; Prevalence; Process; Production; Proteome; Psychological Stress; Rattus; Reporting; Research; Rodent; Role; School Dentistry; Sensory; Severities; Sex Differences; Stress; Structure of trigeminal ganglion; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular joint disorder pain; Testing; Texas; Training; Trigeminal Pain; Trigeminal System; Universities; Woman; career development; cell type; chemokine; craniofacial; cytokine; design; experimental study; glial activation; improved; inflammatory pain; joint stress; male; mechanical allodynia; men; neural; neural circuit; neurobiological mechanism; orofacial; pain behavior; parabrachial nucleus; pre-clinical research; preclinical study; research and development; sensory input; sex; sexual dimorphism; transcriptome; transcriptome sequencing; Affective; Afferent Neurons; Animal Model; Animals; Anterior; Baltimore; Basic Science; Behavioral Assay; Biology; Cells; Chronic stress; Clinical Research; Confocal Microscopy; Craniofacial Pain; Cross Bite; Data; Dentistry; Detection; Doctor of Philosophy; Estrogen Replacements; Experimental Designs; Exposure to; Female; Flow Cytometry; Gene Expression; Genes; Goals; Gonadal Hormones; Immunohistochemistry; Inflammation; Inflammatory; Knowledge; Maryland; Masseter Muscle; Mentorship; Methods; Microglia; Modeling; Modernization; Neurobiology; Neuroglia; Neuronal Plasticity; Neurons; Orofacial Pain; Pain; Pain management; Pathway interactions; Patients; Prevalence; Process; Production; Proteome; Psychological Stress; Rattus; Reporting; Research; Rodent; Role; School Dentistry; Sensory; Severities; Sex Differences; Stress; Structure of trigeminal ganglion; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular joint disorder pain; Testing; Texas; Training; Trigeminal Pain; Trigeminal System; Universities; Woman; career development; cell type; chemokine; craniofacial; cytokine; design; experimental study; glial activation; improved; inflammatory pain; joint stress; male; mechanical allodynia; men; neural; neural circuit; neurobiological mechanism; orofacial; pain behavior; parabrachial nucleus; pre-clinical research; preclinical study; research and development; sensory input; sex; sexual dimorphism; transcriptome; transcriptome sequencing

Abstract Psychological stress is reported to be a trigger and a result of temporomandibular joint disorder (TMJD) pain, creating a vicious cycle that can exacerbate pain in both men and women. For reasons unclear, TMJD and stress are reported to be more prevalent in women. Preclinical research indicates that subchronic to chronic stress can exacerbate pain in male and female subjects, however the role of stress on occlusive TMJD pain and its underlying mechanisms is unclear. It remains possible that there are undetected sex differences in the effects of stress on trigeminal neurobiology which may contribute to the dimorphic prevalence of TMJD pain. One possible mechanism underlying stress exacerbated TMJD pain may be attributed to dimorphic neural organization and/or function of the trigeminal ganglia (TG) sensory neuron afferents to the parabrachial nucleus (PBN). Additionally, or alternatively, glial cells may play a role in the sexually dimorphic modulation of these circuits during TMJD pain. As microglia in the PBN are activated during both stress and orofacial pain and contribute to inflammation, the role of microglia in stress exacerbated TMJD pain in the PBN of males and females remains unknown. A sexually dimorphic effect of stress on TMJD pain may be one factor underlying the greater prevalence of TMJD in women and filling gaps in our knowledge of the neurobiological mechanisms in the trigeminal system contributing to pain is critical to ultimately improving pain management. Our overarching hypothesis is that sex differences in PBN function contribute to stress exacerbated pain behaviors in a rat model of occlusive TMJD. The goals for this F31 will test our working hypothesis across two specific aims: Specific Aim 1 will determine whether neural activity of PBN neurons receiving sensory input from the TMJ contribute to sex differences in stress exacerbated pain behaviors. Specific Aim 2 will determine whether PBN microglia contribute to sex differences in stress exacerbated pain behaviors in a rat model of occlusive TMJD. Experiments designed under these aims will utilize a combination of behavioral assays, immunohistochemistry, confocal microscopy, flow cytometry, multiplex proteome profiler arrays, and gene sequencing to test the role of the PBN in stress exacerbated orofacial pain. Our preliminary data provide strong support for the hypothesis and our results have the potential to fill a major gap in knowledge on the deleterious effects of stress as a significant trigger and result of TMJD pain.

抽象的 据报道，心理压力是触发因素，是颞下颌关节疾病的结果 （TMJD）疼痛，产生一个恶性循环，会加剧男性和女人的疼痛。为了 原因不清楚，据报道，女性更普遍。临床前 研究表明，慢性压力至慢性压力会加剧男性和女性的疼痛 但是，受试者压力在闭塞TMJD疼痛及其潜在机制上的作用是 不清楚。压力对压力的影响仍有未发现的性别差异 三叉神经生物学可能有助于TMJD疼痛的二态流行。一 应力加剧的可能机制加剧TMJD疼痛可能归因于二态 三叉神经节（TG）感觉神经元传入的神经组织和/或功能 副核（PBN）。另外，或者，神经胶质细胞可能在性中发挥作用 TMJD疼痛期间这些电路的二态调节。由于PBN中的小胶质细胞被激活 在压力和口面上的疼痛和导致炎症的过程中，小胶质细胞在压力中的作用 男性和女性PBN的TMJD疼痛加剧仍然未知。性二态 压力对TMJD疼痛的影响可能是TMJD在 妇女并填补了我们对三叉神经生物学机制的了解 导致疼痛的系统对于最终改善疼痛管理至关重要。我们的总体 假设是，PBN功能的性别差异有助于压力加剧的疼痛行为 在闭合TMJD的大鼠模型中。该F31的目标将检验我们的工作假设 两个具体目标：特定目标1将确定是否接受PBN神经元的神经活动 TMJ的感觉输入导致压力加剧疼痛行为的性别差异。 具体目标2将确定PBN小胶质细胞是否促进压力性别差异 闭塞TMJD大鼠模型中的疼痛行为加剧。这些实验在这些下设计 AIMS将利用行为测定，免疫组织化学，共聚焦显微镜的组合， 流式细胞仪，多重蛋白质组探测器阵列和基因测序以测试 压力中的PBN加剧了口面疼痛。我们的初步数据为 假设和我们的结果有可能填补关于有害的知识的重大差距 压力作为重要的触发因素和TMJD疼痛的结果。