VITAMIN D DEFICIENCY CAUSES MUSCULOSKELETAL HYPERSENSITIVITY: THE ROLE OF NOCICEPTOR HYPERINNERVATION
Issue Date
2011-05-31Author
Tague, Sarah Elizabeth
Publisher
University of Kansas
Format
118 pages
Type
Dissertation
Degree Level
Ph.D.
Discipline
Molecular & Integrative Physiology
Rights
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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Show full item recordAbstract
Clinical studies link vitamin D deficiency and musculoskeletal pain, both of which occur more frequently in women. However, a causal relationship has been difficult to establish and it is not clear whether vitamin D metabolites directly influence nociceptors (`pain-sensing' neurons). It was shown here, via immunohistochemistry and western blot, that rat putative nociceptors contain vitamin D receptors (VDRs) and metabolic enzymes, whose expression is regulated by ovarian hormones. In ovariectomized rats a vitamin D deficient diet induces balance deficits and deep tissue mechanical hyperalgesia, concurrent with muscle hyperinnervation by presumed nociceptors. Balance deficits, muscle mechanical hypersensitivity, and hyperinnervation are not corrected by elevated dietary calcium. In primary sensory cultures, VDR is enriched in c-fiber growth cones and regulates neurite outgrowth through VDR rapid response pathways. Therefore, vitamin D metabolites act directly on nociceptive neurons to inhibit axonal sprouting, accounting for hypovitaminosis D-induced muscle hyperinnervation, and possibly contributing to hypersensitivity.
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