Emotion and Memory in Chronic Neuropathic Pain

NCT06518421 | Recruiting

• 1 other identifier: 14-7350
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Trigeminal Neuralgia; Facial Pain

Keywords

Trigeminal Neuralgia; Facial Pain; Emotion; Cognition; Memory

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (5)

• Structural Magnetic Resonance Imaging Cont.

  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)

  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)

• 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)

• Sex- and gender-based analysis (SGBA)

  For HC ad TN > SGBA at baseline as a part of the demographic data

Study Arms (2)

Healthy Controls

Brain imaging, clinical data, and cognitive data will be prospectively collect and analyze in both healthy control and patients with trigeminal neuralgia groups. Prospective data collection for control group includes: * MRI scan (1 timepoint) * Neuropsychological assessments (1 timepoint)

Behavioral: Neuropsychological assessments; Diagnostic Test: MR Imaging

Trigeminal Neuralgia

Trigeminal Neuralgia is the most common chronic neuropathic facial pain disorder, characterized by the sudden onset of intermittent, intense, shock-like pain in distributions of the trigeminal nerve branches. TN has several unique features that distinguish it as an ideal model for the study of chronic pain: TN is largely unilateral; is severe in its nature; has stereotypical presentation among patients; and is not associated with other sensory deficits observed in other chronic pain disorders, such as numbness. Brain imaging, clinical data, and cognitive data will be prospectively collect and analyze in both healthy control and patients with trigeminal neuralgia groups. Prospective data collection for TN group includes: * MRI scan (2 timepoints; pre- and 6-month post-surgery) * Neuropsychological assessments (2 timepoints; pre- and 6-month post-surgery)

Behavioral: Neuropsychological assessments; Diagnostic Test: MR Imaging

Interventions

Neuropsychological assessments BEHAVIORAL

* Pain questionnaires such as Numerical Pain Rating Scale is one of the most widely used multidimensional pain scales to assesses a person's pain based on the words they use to describe their pain. * Battery of Cognitive questionnaires = The cognitive test battery was designed to assess key cognitive abilities including attention, concentration, verbal learning and memory, verbal fluency, working memory and executive function as well as global cognitive functioning and fear and anxiety * Mnemonic Simulation Test and Rey Auditory Verbal Learning Test are the neuropsychological assessments designed to evaluate recognition and verbal memory, respectively. Both tasks have been shown to be very sensitive to hippocampal engagement and damage. * Memory-recall interview is an interview for the interviewees to recall the event from different perspectives, such as from the preadmission date, 2-week post- and 6-month post-surgical date. This supports the memory retrieval process.

Healthy Controls; Trigeminal Neuralgia

MR Imaging DIAGNOSTIC_TEST

Magnetic Resonance Imaging is a noninvasive medical imaging test that produces detailed images of almost every internal structure in the human body, including the organs, bones, muscles and blood vessels. MRI scanners create images of the body using a large magnet and radio waves.

Healthy Controls; Trigeminal Neuralgia

Eligibility Criteria

• Age: 35 Years - 60 Years
• Gender Eligibility Details: All gender identify including in Male, Female, Intersex, Bisexual, Asexual/Allies, Lesbian, Gay, Transgender/Transexual, Queer/Questioning, Cisgender, Non-binary, Genderqueer, Two-spirit, and Gender neutral are welcome to participate in this study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

* Healthy control will be recruited from the local community * Patients with Trigeminal neuralgia will be recruited through our Neurosurgery and Pain Clinic at Toronto Western Hospital, University Health Network

You may qualify if:

• Age between 35 and 60 years old
• Absence of other active major neurological or psychiatric disorders
• Absence of MRI contraindications
• Able to communicate sufficiently to complete tasks and questionnaires
• Montreal Cognitive Assessment (MoCA) score greater than 23/30 (MoCA ≤23/30 could indicate severe cognitive impairment)
• Experiencing TN pain over a period of 6 months
• Stable medication use
• Meet established diagnostic criteria for TN (ICHD-3)

You may not qualify if:

• Presence of other chronic pain/headache conditions
• Untreated hypertension or diabetes mellitus
• History of chronic drug or substance use disorder, chronic use of opioids or steroids, head trauma affecting cognitive performance,
• History/presence of active psychiatric illness and/or current use of psychoactive medication
• History of multiple sclerosis, skull base injury or tumours

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T2S8, Canada

RECRUITING

Related Publications (6)

• Noorani A, Hung PS, Zhang JY, Sohng K, Laperriere N, Moayedi M, Hodaie M. Pain Relief Reverses Hippocampal Abnormalities in Trigeminal Neuralgia. J Pain. 2022 Jan;23(1):141-155. doi: 10.1016/j.jpain.2021.07.004. Epub 2021 Aug 8.

  PMID: 34380093 RESULT

• Hung PS, Noorani A, Zhang JY, Tohyama S, Laperriere N, Davis KD, Mikulis DJ, Rudzicz F, Hodaie M. Regional brain morphology predicts pain relief in trigeminal neuralgia. Neuroimage Clin. 2021;31:102706. doi: 10.1016/j.nicl.2021.102706. Epub 2021 May 25.

  PMID: 34087549 RESULT

• Vaculik MF, Noorani A, Hung PS, Hodaie M. Selective hippocampal subfield volume reductions in classic trigeminal neuralgia. Neuroimage Clin. 2019;23:101911. doi: 10.1016/j.nicl.2019.101911. Epub 2019 Jun 26.

  PMID: 31491821 RESULT

• Audrain S, McAndrews MP. Schemas provide a scaffold for neocortical integration of new memories over time. Nat Commun. 2022 Oct 2;13(1):5795. doi: 10.1038/s41467-022-33517-0.

  PMID: 36184668 RESULT

• Waisman A, Pavlova M, Noel M, Katz J. Painful reminders: Involvement of the autobiographical memory system in pediatric postsurgical pain and the transition to chronicity. Can J Pain. 2022 Jun 3;6(2):121-141. doi: 10.1080/24740527.2022.2058474. eCollection 2022.

  PMID: 35692557 RESULT

• Noel M, Rosenbloom B, Pavlova M, Campbell F, Isaac L, Page MG, Stinson J, Katz J. Remembering the pain of surgery 1 year later: a longitudinal examination of anxiety in children's pain memory development. Pain. 2019 Aug;160(8):1729-1739. doi: 10.1097/j.pain.0000000000001582.

  PMID: 31335643 RESULT

Related Links

• MedlinePlus related topics: Trigeminal Neuralgia
• Genetic and Rare Disease Information Center Resources: Trigeminal Neuralgia

MeSH Terms

Conditions

Trigeminal Neuralgia; Facial Pain

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Trigeminal Nerve Diseases; Facial Neuralgia; Facial Nerve Diseases; Mouth Diseases; Stomatognathic Diseases; Cranial Nerve Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Mojgan Hodaie, MD, MSc

  Department of Neurosurgery, Toronto Western Hospital, University Health Network

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacob Kim, BSc

CONTACT

4163404907; jacob.kim@uhn.ca

Patcharaporn Srisaikaew, PhD

CONTACT

4163404907; patcharaporn.srisaikaew@uhn.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: July 24, 2024
• Study Start: February 12, 2024
• Primary Completion (Estimated): February 12, 2027
• Study Completion (Estimated): February 12, 2029
• Last Updated: July 24, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)