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Nanomedicine-Driven Neuropathic Pain...

Saleem, Muzamil .

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Nanomedicine-Driven Neuropathic Pain Relief in Rat Model Is Associated with Macrophage Polarity and Mast Cell Activation.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Nanomedicine-Driven Neuropathic Pain Relief in Rat Model Is Associated with Macrophage Polarity and Mast Cell Activation./
作者:	Saleem, Muzamil .
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	132 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-07, Section: B.
Contained By:	Dissertations Abstracts International81-07B.
標題:	Biology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13895355
ISBN:	9781392353240

Nanomedicine-Driven Neuropathic Pain Relief in Rat Model Is Associated with Macrophage Polarity and Mast Cell Activation.
Saleem, Muzamil .

Nanomedicine-Driven Neuropathic Pain Relief in Rat Model Is Associated with Macrophage Polarity and Mast Cell Activation. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 132 p.

Source: Dissertations Abstracts International, Volume: 81-07, Section: B.

Thesis (Ph.D.)--Duquesne University, 2019.

This item must not be sold to any third party vendors.

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve, by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye), and is small enough to be phagocytosed by circulating monocytes. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, and is the rationale for intravenous delivery at this time-point. Pain relief is evident within 24 hours, lasting approximately 6 days. The ipsilateral sciatic nerve and associated L4 and L5 dorsal root ganglia (DRG) tissue of both nanomedicine and control (nanoemulsion without drug) treated animals was investigated by immunofluorescence and confocal microscopy at the peak of pain relief (day-12 post-surgery), and when pain-like hypersensitivity returns (day-18 post-surgery). At day-12, a significant reduction of infiltrating macrophages, mast cells and mast cell degranulation was observed at the sciatic nerve following treatment. In the DRG, there was no effect of treatment at both day-12 and day-18. Conversely, at the DRG, there is a significant increase in macrophage infiltration and mast cell degranulation at day-18. The treatment effect on immune pathology in the sciatic nerve was investigated further by assessing the expression of macrophage cyclooxygenase-2 (COX-2)-the drug target-and extracellular prostaglandin E2 (PGE2), as well as the proportion of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages. At day-12, there is a significant reduction of COX-2 positive macrophages, extracellular PGE2, and a striking reversal of macrophage polarity. At day-18, these measures revert to levels observed in control-treated animals. Here we present a new paradigm of immune neuropathology research, by employing a nanomedicine to target a mechanism of neuropathic pain-resulting in long-lasting pain relief--whilst revealing novel immune pathology at the injured nerve and associated DRG.

ISBN: 9781392353240Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

Chronic pain

Nanomedicine-Driven Neuropathic Pain Relief in Rat Model Is Associated with Macrophage Polarity and Mast Cell Activation.
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