Emotion and Memory in Chronic Neuropathic Pain

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.

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:

1. To characterize abnormalities in HPC subfields and their associated link with memory-specific performance in TN patients and their potential resolution following surgery.
2. 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.
3. 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.

Methods/Approaches/Expertise The investigators will prospectively analyze brain imaging, clinical, and cognitive data from 340 participants (170 TN and 170 healthy age-/sex-matched controls). Patients will be scanned and assessed pre- and 6 months post-surgical treatment for TN.

In Aim 1, HPC subfield volumes will be extracted to characterize regional abnormalities in TN patients. The investigators will use HPC-sensitive memory tasks, including the mnemonic similarity task and the Rey Auditory Verbal Learning Test , to explore whether the HPC-specific memory processes correlate with structural abnormalities outlined.

In Aim 2, AMG nuclei volumes will be extracted to characterize regional abnormalities in TN patients. Fear of pain questionnaires and the Pain Catastrophizing Scale will be used to explore the link between pain-related fear and chronic pain.

In Aim 3, a validated fMRI task designed for episodic simulation based on novel word-pain associations will be used to examine the relationship between the abnormalities in the HPC subfields and AMG nuclei, and emotion-memory processes in TN patients pre- and post-surgery.

The NPA is a neurosurgeon and scientist with a strong clinical research focus on chronic pain. The team has expertise in chronic pain, brain imaging, cognition, and multivariate statistics.

Expected Outcomes Our innovative proposal interfaces brain imaging with cognition. Knowledge of the relationships between limbic structures, cognition, and pain will revolutionize pain assessment and treatment decisions. Uncovering neural mechanisms of HPC- and AMG-related structures in pain may improve healthcare delivery and patient outcomes by providing objective insights complementing current clinical care.

Eligibility Criteria:
Inclusion Criteria (for HC and TN):

* 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)

Inclusion Criteria for TN:

* Experiencing TN pain over a period of 6 months
* Stable medication use
* Meet established diagnostic criteria for TN (ICHD-3)

Exclusion Criteria (both HC and TN):

* 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