The Neurochemical Phenotype of Sensory Somata with Sympathetic Plexuses – The Role of Nerve Growth Factor
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Authors
Alsaadi, Hanin
Date
2024-04-30
Type
thesis
Language
eng
Keyword
Nerve growth factor , Nociceptors , Chronic pain , Sensory neurons , Sympathetic plexuses , Transgenic mouse model , Trigeminal ganglia , Dorsal root ganglia , Nerve injury
Alternative Title
Abstract
Following peripheral nerve injury, postganglionic sympathetic axons aberrantly sprout towards sensory ganglia where they form perineuronal sympathetic plexuses (basket-like structures) around medium- to large-diameter neurons. This pathological phenomenon is known as sympathosensory coupling and underlies sympathetically-maintained pain. A large body of scholarly literature establishes the critical role of nerve growth factor (NGF) as a primary driver triggering sympathetic sprouting. One important question facing researchers is identifying the precise neurochemical phenotype of the neurons surrounded by sympathetic plexuses. A challenge arises as many phenotypic markers that identify sensory neuronal populations are down-regulated in response to nerve injury.
This work utilized a broad range of nociceptive phenotypic biomarkers to neurochemically phenotype those sensory somata surrounded by sympathetic plexuses. The studies employed quantitative immunofluorescence staining analyses in two distinct models: 1) adult transgenic mice that overexpress NGF, which results in the spontaneous formation of sympathetic plexuses (i.e., absence of injury) in the trigeminal ganglia (TG), and, 2) adult rats and adult mice with peripheral nerve injury, which results in the aberrant formation of sympathetic plexuses in the affected dorsal root ganglia (DRG).
This thesis shows that sympathetic axons target a precise sub-population of NGF-sensitive and peptidergic nociceptors (i.e., those co-expressing the NGF receptor trkA and calcitonin gene-related peptide, CGRP). These trkA+/CGRP+ nociceptive neurons are immunopositive for ATP/purinergic receptor (P2X3) and for neurofilament heavy chain (NFH). The results also suggest that sympathetic plexuses may trigger shifts in the phenotypic expression of other nociceptive biomarkers.
Collectively, this work reveals, for the first time, that sympathosensory sprouting is not a random event but is one that results from sympathetic axons targeting particular subpopulations of nociceptive neurons in the sensory ganglia (i.e., those displaying specific neurochemical features among the trkA+/CGRP+ subgroups). The identification of this specificity is novel and contributes to our understanding of the mechanisms underlying pathological sympathosensory coupling. Ultimately, these findings may contribute to targeted therapeutic interventions in the context of sympathetically-maintained pain, in particular as it relates to the aberrant formation of sympathetic plexuses around subpopulations of nociceptive sensory somata that rely on the availability of target-derived NGF for survival and maintenance in adulthood.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.