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Characterization of gammadelta T cells in peripheral nociception and inflammatory pain hypersensitivity
Başlık:
Characterization of gammadelta T cells in peripheral nociception and inflammatory pain hypersensitivity
Yazar:
Petrovic, Jelena, author.
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (76 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-07C.
Advisors: Nader Ghasemlou.
Özet:
Inflammatory pain can occur following tissue insult, bacterial infection, arthritis and various autoimmune diseases and is initiated and maintained by a well-orchestrated response of recruited and tissue-resident immune cells. When activated, these immune cells secrete inflammatory factors that have the capability to modulate pain through excitation of nociceptive primary afferent sensory neurons (nociceptors). Current treatments for inflammatory pain include NSAIDs and opioids, which provide modest, short-term benefits, but adverse side effects. Thus, there is a need for novel, safe and efficacious treatments for inflammatory pain.
It is increasingly clear in the literature that interactions between nociceptors and immune cells regulate pain. The use of cell depletion strategies is necessary in order to assess the involvement of immune cells in inflammatory pain in pre-clinical studies. Previous work has considered the contribution of mast cells, gammadelta T cells, neutrophils, monocytes and macrophages to inflammatory pain outcomes, and only a subset of myeloid cells were necessary contributors to mechanical hypersensitivity outcomes, but not thermal hypersensitivity.
We sought to understand the contribution of skin-resident gammadelta T cells in nociception and inflammatory pain. To achieve this, we used wild-type (TCRdelta+/+), heterozygous (TCRdelta+/-) and knock-out (TCRdelta-/-) mice to determine if there is a link between gammadelta T cells and pain outcomes. Mouse responsiveness to pain was assessed using behavioural tests to measure mechanical and thermal sensitivity in both male and female TCR? mice, before and after injury. The characterization of these cells in naive animals demonstrated that gammadelta T cells are not necessary for modulating mechanical and thermal sensitivity in male or female mice, excluding the female response to high heat stimuli (55°C). Using three inflammatory pain models (formalin, incisional wound and Complete Freund's adjuvant), hypersensitivity outcomes between TCRdelta strains did not differ in their responses to mechanical and thermal stimuli after injury. Together, these results suggest that gammadelta T cells do not contribute directly to peripheral nociception and inflammatory pain in mice. Future studies should consider other skin-resident immune cells and their secreted factors as they may provide alternative results and potentially novel therapeutic targets for inflammatory pain.
Notlar:
School code: 0283
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
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XX(684143.1) | 684143-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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