Age and Sex Dependent Hippocampal Normalization After Pain Relief in Trigeminal Neuralgia
Poster No:
2157
Submission Type:
Abstract Submission
Authors:
Jerry Li1, Kaylee Sohng1, Timur Latypov1, Alborz Noorani1, Patcharaporn Srisaikaew2, Peter Hung1, Daniel Jorgens2, Mojgan Hodaie2
Institutions:
1University of Toronto, Toronto, Ontario, 2University Health Network, Toronto, Ontario
First Author:
Co-Author(s):
Introduction:
Chronic pain is a silent epidemic. Individuals with trigeminal neuralgia (TN), the most common form of chronic neuropathic facial pain, show evidence of abnormalities within the hippocampus. Microvascular decompression (MVD) is a highly effective surgery to treat TN pain and patients who undergo the procedure are generally young. Thus, it serves as a valuable platform to investigate the dynamics of grey matter alterations and provides insight into how the brain recovers from chronic pain. Previously, we found that reduced hippocampal volume in TN was reversed upon pain relief following successful surgery. However, the roles of age and sex in hippocampal normalization remain unclear. We hypothesized that hippocampal recovery would be biased towards females of younger age.
Methods:
Magnetic resonance imaging (MRI) scans of 50 MVD patients (14 males, 36 females) were collected before and 6-months after surgery. Subjects were age- and sex-matched with healthy controls from the Cambridge Centre for Neuroscience and Ageing (Cam-CAN). TN subjects rated their pain pre- and post-surgery on a numeric rating scale from 0 (no pain) to 10 (worst pain imaginable). 41 (82%) responded to the surgery, with a post-surgical decrease in pain rating of at least 75%. FreeSurfer 7.0 was used to segment the hippocampus into 10 bilateral regions. Head size differences were adjusted for using a generalized linear model of the form "ROI ~ Group + Age + Sex + SGV", where ROI is the hippocampal region of interest, group is one of healthy controls, pre- or post-surgery, age is continuous, sex is binary-coded, and SGV is the subcortical grey matter volume or covariate. Models with lower AIC and BIC were selected and checked for goodness-of-fit. Hippocampal volumes were compared using independent and paired t-tests and checked for a relationship with age using Spearman correlation tests. All relevant p-values were corrected for multiple comparisons using the false discovery rate to become q-values, with α = 0.05. All data were analyzed in R 4.3.2 and validated in Python 3.11.5.
Results:
At both pre- and post-surgical time points, males had larger bilateral hippocampi than females (q = 0.029). Notably, following MVD, females 50 years and younger (n = 12) had significant increases in total left-hemispheric hippocampal volume (q = 0.02) to a level comparable to controls. This included 6/9 of its subregions (dentate gyrus, CA3 and CA4, molecular layer, hippocampal head and body), and the right hippocampal head. Furthermore, a gradient of normalization was observed, in that younger females had a greater degree of normalization compared to females closer to the age of 50 (ρ = -0.62, p = 0.032). Similarly, in females with right-sided facial pain (n = 18), normalization was overwhelmingly (5/10 regions) in the contralateral hemisphere, including the whole left hippocampus (q = 0.038), while no regions in the right hemisphere significantly increased. No significant changes were observed in male responders nor in female responders over 50 years of age.
Conclusions:
These results are another instance of sex-related effects in neuropathic pain, with an inflection point at the age of 50 in females, beyond which hippocampal normalization was no longer observed. Traditionally known for its role in memory, cognition, and emotions, we provide further evidence that the hippocampus may be a key structure of interest in chronic pain conditions. These findings support a pressing need to expedite clinical timelines for females with TN, as they experience significantly greater delays in receiving surgical treatment than males. Additionally, non-invasive measures like age, sex, and hippocampal volume may have predictive value for grey matter recovery following MVD. Ultimately, knowing that brain abnormalities in chronic pain can be reversed with pain relief presents promising new avenues for future pain research, with a focus on equitable patient treatment.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Lifespan Development:
Aging
Modeling and Analysis Methods:
Segmentation and Parcellation
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures 1
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 2
Keywords:
Aging
Computational Neuroscience
Nerves
Pain
Peripheral Nerve
Segmentation
Sexual Dimorphism
STRUCTURAL MRI
Structures
Sub-Cortical
1|2Indicates the priority used for review
Provide references using author date format
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