The aim of this thesis study was to investigate the substance P (SP)-immunoreactive (IR) sensory fiber innervation of CNS target tissues in two experimental models. In the first model, we examined the SP-IR boutons apposed to three functional types of dorsal horn neurons and their morphological interaction with calcitonin gene-related peptide (CGRP) and enkephalin (ENK) in the cat spinal cord, using a combination of intracellular electrophysiological recording and horseradish peroxidase injection with ultrastructural immunocytochemistry. In addition to SP-IR only boutons, we detected boutons co-localizing SP plus CGRP and SP plus ENK immunoreactivities presynaptic to nociceptive neurons. Quantitatively, significantly higher numbers of SP-IR, SP+CGRP-IR and SP+ENK-IR boutons were apposed to nociceptive neurons. Non-nociceptive neurons were rarely innervated by boutons which were SP-IR, SP+CGRP-IR and SP+ENK-IR. In contrast, ENK-IR only boutons innervated non-nociceptive neurons considerably. Boutons co-localizing SP and CGRP were considered as originating from primary sensory afferents. Most nociceptive neurons contained ENK immunoreactivity, but non-nociceptive neurons were never ENK-IR. The interaction of SP and $ gamma$-aminobutyric acid (GABA) in the superficial dorsal horn of the cat and rat spiral cord was also investigated. The co-localization of SP and GABA in axonal terminals was detected for the first time in the superficial layers of the dorsal horn of the cat, but not rat, spinal cord. / In the second model, we used immunocytochemistry to study the SP-IR fiber innervation of the white matter of transgenic mice expressing NGF in myelinating oligodendrocytes driven by a MBP promoter. SP-IR fibers were observed in the white matter of the CNS of both transgenic and control mice from postnatal day 0 to day 2. From day 5 on, however, these SP-IR fibers increased markedly to become ectopic fibers in transgenic mice, but decreased dramatically, and finally disappeared, in control mice. The ectopic SP-IR fibers of transgenic mice persisted throughout adulthood. Capsaicin treatment abolished all ectopic SP-IR fibers, indicating their primary sensory origin. / In conclusion, SP-IR fibers specifically innervated nociceptive neurons and co-localized with CGRP, ENK and GABA in the cat dorsal horn. The finding provides anatomical substrates for roles of SP in nociception and for functional interactions of SP with ENK and GABA. Ectopic SP-IR fibers innervated the white matter of the CNS of transgenic mice where NGF was abnormally-produced.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.40185 |
| Date | January 1995 |
| Creators | Ma, Weiya |
| Contributors | Ribeiro-Da-Silver, A. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001481132, proquestno: NN12424, Theses scanned by UMI/ProQuest. |
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