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The Effect of Lumbar Spine Osteoarthritis on the Manifestation of Central Sensitization and Neurogenic Inflammation in Musculoskeletal Tissues in Rats

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Title: The Effect of Lumbar Spine Osteoarthritis on the Manifestation of Central Sensitization and Neurogenic Inflammation in Musculoskeletal Tissues in Rats
Author: Coutinho Kullmann Duarte, Felipe
Department: Department of Human Health and Nutritional Sciences
Program: Neuroscience
Advisor: Srbely, John
Abstract: Symmetrical bilateral spread of neurogenic inflammation (NI) has been shown as a secondary response post experimental primary osteoarthritis (OA) and pelvic organ inflammation. This manifestation requires participation of sensitization of the central nervous system and antidromic release of neuropeptides through peripheral afferents. However, knowledge regarding the presence of neurogenic mechanism in heterologous tissues is limited. The overall aim of this thesis was to investigate the presence of neuropeptides related to NI in heterologous knee and quadriceps muscle tissue as a response of experimentally-induced lumbar facet OA disorder. Study 1 of this thesis showed greater substance P (SP) immune-expression within heterologous tibiofemoral cartilage following by lumbar spine-induced OA compared to sham and naïve groups. The SP immunoreactivity was higher at superficial cartilage zone and was accompanied by consistent loss of superficial zone chondrocytes, mild roughening of the articular surface and occasional chondrocyte clusters, changes associated with early OA development. Study 2 investigated the association between naturally occurring lumbar spine OA in elderly rats (L3-L5), SP protein expression at the level of the spinal cord (L4-L5), and the presence of NI within neurosegmentally-linked quadriceps (L2-L5) in elderly rats versus young rats. Elderly OA rats had significantly higher protein expression of SP within the dorsal horn, and higher protein expression of SP and protease-activated receptor 2 (PAR2) within the quadriceps muscle. Similar findings were not seen within the young rat population. Study 3 aimed to follow up with a rationalization for the associative findings of study two by exploring the causal-effect of experimentally induced spine facet OA and NI and intracellular kinases within a neurosegmentally-linked myotome. The findings of this study provided evidence that lumbar spine OA increases NI and intracellular kinases only within neurosegmentally-related myotomes but not in remote myotomes. Collectively, these findings support the manifestation of central sensitization and NI within the heterologous knee cartilage and within neurosegmentally-linked myotomes as a secondary response after the induction of a primary lumbar spine OA disorder in rats. These findings may have significant implications for advancing our understanding of the pathophysiology of chronic musculoskeletal disorders such as OA and myofascial pain syndrome.
Date: 2019-01
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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Attribution-NonCommercial-NoDerivatives 4.0 International Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International