The Role of Limbic Subcortical Structures and Cognition in Chronic Neuropathic Pain
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Behavioural Inhibition System
研究概览
简要总结
Chronic pain affects one in four Canadians, leading to severe personal and societal costs. Over 70% of chronic pain patients report memory difficulties and fear having unexpected pain. Abnormalities in brain structures associated with emotion and memory, including the hippocampus and amygdala, can be affected by chronic pain. Understanding the relationship between chronic pain, structural brain changes, and cognitive functioning will lead to improved diagnosis, treatment, and outcomes in chronic pain disorders. In this project, the investigators will use advanced brain imaging techniques that assess the structure and function of the brain along with cognitive assessments to examine the overlap between chronic pain and emotion-memory processes. The study team will conduct the study using an excellent model of chronic pain-trigeminal neuralgia, a severe form of facial pain that responds well to surgical treatment. Brain images and cognitive data will be collected from participants before and after surgical treatment for pain. This information will be analyzed and compared with age- and sex-matched healthy individuals. This study will be the first to thoroughly investigate relationships between brain structure and function, cognition (memory, emotion), and promises to impact our understanding of chronic neuropathic pain conditions.
详细描述
Chronic pain affects 1 in 4 Canadians leading to severe personal and societal consequences. Over 70% of patients with chronic pain report cognitive deficits including memory difficulties and fear of having unexpected pain. However, the impact of chronic pain on cognition has not been adequately studied. Trigeminal neuralgia (TN), a severe facial pain with clear surgical outcomes, is an ideal model to address this question. Limbic structures, including the hippocampus (HPC) and amygdala (AMG), link emotion-memory and pain. Our prior CIHR-funded research revealed significant HPC volume reduction that normalized with successful treatment and abnormal HPC activity and AMG volume in chronic pain. These findings provide the foundation for a better understanding of the limbic subcortical structures and neuronal mechanisms of chronic pain.
Multimodal neuroimaging techniques have emerged as important tools for studying brain abnormalities in TN - seeking to elucidate the underlying neural mechanisms of HPC and AMG alterations, along with emotion-memory processes. This will be the first comprehensive study of limbic subcortical structural alterations and cognition in chronic pain.
Goal(s)/Research Aims
Our overall goal is to uncover the underlying neural mechanism of HPC and AMG alteration in TN and how these relate to chronic pain pathophysiology and cognition. Our specific aims are:
- To characterize abnormalities in HPC subfields and their associated link with memory-specific performance in TN patients and their potential resolution following surgery.
- To investigate the role of the AMG in pain-related fear in TN patients pre- and post-surgery and their associated link with the treatment outcomes.
- To determine the relationship between the alterations in HPC subfields and the amygdaloid complex, and emotion-memory processes in TN patients pre- and post-surgery.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 35 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Behavioural Inhibition System
时间窗: For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria
The Behavioural Inhibition System (BIS) will be included in our battery of neuropsychological assessments that will be conducted on both HC and TN groups to screen for study inclusion and exclusion criteria. The BIS is a 20 question, self-assessment that measures trait sensitivity levels of the behavioral inhibition and activation systems.
Beck's Hopelessness Scale
时间窗: For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria
The Beck Hopelessness Scale (BHS) will be included in our battery of neuropsychological assessments that will be conducted on both HC and TN groups to screen for study inclusion and exclusion criteria.
Childhood Trauma Questionnaire
时间窗: For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria
The Childhood Trauma Questionnaire (CTQ) will be included in our battery of neuropsychological assessments that will be conducted on both HC and TN groups to screen for study inclusion and exclusion criteria.
Pain Catastrophizing Scale
时间窗: For HC > pain-related fear and anxiety assessments at baseline. For TN >> pain-related fear and anxiety assessments at baseline (pre-surgery) and at 6-month post-surgical
The Pain Catastrophizing Scale (PCS) will be used as one of the pain-related fear and anxiety assessments to assess pain-related fear and anxiety in TN and HC groups. The investigators will assess whether the abnormalities of the AMG nuclei volume will be normalized after surgery and will correlate these findings with validated pain-related fear and anxiety assessments. The PCS will help investigators quantify an individual's pain - how they feel and what they think about when experiencing something painful.
Beck Depression Inventory
时间窗: For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria
The Beck Depression Inventory (BDI) will be included in our battery of neuropsychological assessments that will be conducted on both HC and TN groups to screen for study inclusion and exclusion criteria. The BDI consists of 21 questions on which patients must score themselves on a scale from zero to three. The BDI is scored out of 63 with a score over 31 representing severe depression.
Pain Anxiety Symptoms Scale
时间窗: For HC > pain-related fear and anxiety assessments at baseline. For TN >> pain-related fear and anxiety assessments at baseline (pre-surgery) and at 6-month post-surgical
The Pain Anxiety Symptoms Scale (PASS-20) will be used as one of the pain-related fear and anxiety assessments to assess pain-related fear and anxiety in TN and HC groups. The investigators will assess whether the abnormalities of the AMG nuclei volume will be normalized after surgery and will correlate these findings with validated pain-related fear and anxiety assessments. The Pass-20 is a 20 item assessment that measures 4 distinct components of pain-related anxiety.
Anxiety Sensitivity Index
时间窗: For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria
The Anxiety Sensitivity Index (ASI) will be included in our battery of neuropsychological assessments that will be conducted on both HC and TN groups to screen for study inclusion and exclusion criteria. The ASI is a six item scale that can outline different concerns someone could have regarding their anxiety.
Structural magnetic resonance imaging (MRI)
时间窗: For HC > MRI at baseline. For TN > MRI at baseline (pre-surgery) and at 6-month post-surgical)
The investigators will acquire prospective longitudinal structural imaging data in 170 Trigeminal Neuralgia (TN) (pre-/6-months post-surgery) and 170 healthy controls (HC) and obtain topologies and volumes of the hippocampus (HPC) subfields using the brain imaging analysis software including HippUnfold and FreeSurfer. The investigators will also analyze amygdala (AMG) nuclei volumes using FreeSurfer. The group comparisons of the HPC and AMG will be done in both inter-group (TN vs. HC) and intra-group (pre- vs. post-surgery).
Mnemonic Similarity Test
时间窗: For HC > MRI at baseline. For TN > MRI at baseline (pre-surgery) and at 6-month post-surgical)
The Mnemonic Similarity Test will be used to compare HPC-dependent memory performance between TN and HC and examine the effect of surgery (pre- and post-) on performance. The investigators will assess whether HPC-dependent memory and HPC volumes/topologies normalize following surgical TN pain relief.
Recalled pain memory interview
时间窗: For HC > recalled pain at baselines. For TN >> recalled pain at baseline (pre-surgery) and at 2 weeks and 6-month post-surgery
The recalled pain interview, focused on the recall of pain events, will be conducted and analyzed with a specific focus on the discrepancies in pain recall (referred to as autobiographical memory, AM). Recalled Pain questionnaires will take place at baseline (\~1 week prior to surgery, for the recall of pain onset and experience), acute recovery (2 weeks post-surgery) and 6 months post-surgery for recalled pain. These interview questionnaires will assess pain frequency, duration, intensity, fear, anxiety, unpleasantness, and interference.
Marlowe Crowne Scale
时间窗: For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria
The Marlowe Crowne Scale (MCS) will be included in our battery of neuropsychological assessments that will be conducted on both HC and TN groups to screen for study inclusion and exclusion criteria.
Fear of Pain Questionnaire III
时间窗: For HC > pain-related fear and anxiety assessments at baseline. For TN >> pain-related fear and anxiety assessments at baseline (pre-surgery) and at 6-month post-surgical
The Fear of Pain Questionnaire III (FPQ-III) will be used as one of the pain-related fear and anxiety assessments to assess pain-related fear and anxiety in TN and HC groups. The investigators will assess whether the abnormalities of the AMG nuclei volume will be normalized after surgery and will correlate these findings with validated pain-related fear and anxiety assessments. The FPQ-III is a 30 item assessment on which individuals rate how fearful they are of certain pain experiences on a scale from one to five.
State-Trait Anxiety Inventory
时间窗: For HC > pain-related fear and anxiety assessments at baseline. For TN >> pain-related fear and anxiety assessments at baseline (pre-surgery) and at 6-month post-surgical
The State-Trait Anxiety Inventory (STAI) will be used as one of the pain-related fear and anxiety assessments to assess pain-related fear and anxiety in TN and HC groups. The investigators will assess whether the abnormalities of the AMG nuclei volume will be normalized after surgery and will correlate these findings with validated pain-related fear and anxiety assessments. The STAI is commonly used to measure trait and state anxiety. This assessment consists of 20 items for assessing trait anxiety and 20 for state anxiety, each of which are rated on a 4-point scale.
Functional Magnetic Resonance Imaging (fMRI)
时间窗: For HC >ES task-fMRI at baseline. For TN >> ES task-based fMRI at baseline (pre-surgery) and 6-months post-surgery
The experimental functional magnetic resonance imaging (fMRI) task that is specifically designed to measure episodic simulation (ES) using both neutral and pain-related cues will be conducted. ES measures the capacity to imagine specific future personal events and is heavily dependent on limbic integrity. This, along with the recalled pain memory interview will allow the investigators to correlate task-based fMRI findings with pain-recall discrepancies (discrepancies between recalled and initial pain ratings) and surgical response.
次要结局
- The Rey Auditory Verbal Learning Test (RAVLT)(For HC > RAVLT at baseline. For TN > RAVLT at baseline (pre-surgery) and at 6-month post-surgical))
- Whole brain cortical-based analysis(For HC > MRI at baseline. For TN > MRI at baseline (pre-surgery) and at 6-month post-surgical))
- Sex- and gender-based analysis (SGBA)(For HC ad TN > SGBA at baseline as a part of the demographic data)
- Structural Magnetic Resonance Imaging Cont.(For HC > MRI at baseline. For TN > MRI at baseline (pre-surgery) and at 6-month post-surgical))
- Impact of COVID-19 on pain population(For HC > COVID-19 related data at baseline. For TN > COVID-19 related data at baseline (pre-surgery) and at 6-month post-surgical))
研究者
Mojgan Hodaie
Senior Scientist
University Health Network, Toronto