Emotion and Memory in Chronic Neuropathic Pain
NCT Number: NCT06518421
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Trigeminal Neuralgia|Facial Pain
Interventions: BEHAVIORAL: Neuropsychological assessments|DIAGNOSTIC_TEST: MR Imaging
Sponsor: University Health Network, Toronto
Sex: ALL
Age: ADULT
Enrollment: 400
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-02-12
Completion Date: 2029-02-12
Locations: Toronto Western Hospital, Toronto, Ontario, M5T2S8, Canada

Summary:
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.

Primary Outcome Measures: Beck Depression Inventory, 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., For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria|Behavioural Inhibition System, 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., For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria|Anxiety Sensitivity Index, 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., For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria|Beck's Hopelessness Scale, 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., For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria|Marlowe Crowne Scale, 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., For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria|Childhood Trauma Questionnaire, 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., For HC and TN > Neuropsychological assessments at baseline to screen for inclusion/exclusion criteria|Structural magnetic resonance imaging (MRI), 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)., For HC > MRI at baseline. For TN > MRI at baseline (pre-surgery) and at 6-month post-surgical)|Mnemonic Similarity Test, 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., For HC > MRI at baseline. For TN > MRI at baseline (pre-surgery) and at 6-month post-surgical)|Fear of Pain Questionnaire III, 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., 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|Pain Catastrophizing Scale, 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., 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|State-Trait Anxiety Inventory, 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., 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|Pain Anxiety Symptoms Scale, 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., 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|Functional Magnetic Resonance Imaging (fMRI), 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., For HC >ES task-fMRI at baseline. For TN >> ES task-based fMRI at baseline (pre-surgery) and 6-months post-surgery|Recalled pain memory interview, 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., For HC > recalled pain at baselines. For TN >> recalled pain at baseline (pre-surgery) and at 2 weeks and 6-month post-surgery
Secondary Outcome Measures: Structural Magnetic Resonance Imaging Cont., Group correlation between other AMG nuclei volumes and pain-related fear and anxiety questionnaires will be performed. The investigators will assess whether the abnormalities of other AMG nuclei volumes will be normalized after surgery and/or correlated with the validated pain-related fear and anxiety assessments., For HC > MRI at baseline. For TN > MRI at baseline (pre-surgery) and at 6-month post-surgical)|The Rey Auditory Verbal Learning Test (RAVLT), Group correlation between other HPC subfield volumes and a second HPC-specific memory task using the Rey Auditory Verbal Learning Test (RAVLT) will be performed to evaluate multiple episodic memory functions in both inter-group (TN vs. HC) and intra-group (pre- vs. post-surgery)., For HC > RAVLT at baseline. For TN > RAVLT at baseline (pre-surgery) and at 6-month post-surgical)|Whole brain cortical-based analysis, Group comparisons of other limbic structures will be performed, using the whole brain cortical-based analysis with a focus on the thickness of the anterior cingulate (ACC), insular, and medial prefrontal cortex (mPFC) cortices. The investigator will be focused on the dynamic changes of the cortical thickness in TN between i) TN vs. HC, and ii) pre- vs. post-surgical time points., 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, Medical and medication history including COVID-19-related experiences will be collected. The investigator will also address the biopsychological impacts of COVID-19 in our study cohort., For HC > COVID-19 related data at baseline. For TN > COVID-19 related data at baseline (pre-surgery) and at 6-month post-surgical)|Sex- and gender-based analysis (SGBA), The investigator will target enrollment of a 50% male-to-female ratio. The investigator will also collect the gender identity data. SGBA will be conducted in all Aims and the distribution of gender data will determine whether we have sufficient power for detailed analyses., For HC ad TN > SGBA at baseline as a part of the demographic data