<p> Osteoarthritis (OA) is the most common arthritis, and the second most common
diagnosis leading to disability. While loss of joint function is disabling, patients report
that the greatest disabler of OA is the pain. Unfortunately, OA pain remains an unmet
medical need. Numerous mechanisms have been proposed for the pathogenesis of OA
pain. However, none of these mechanisms has led to satisfactory evidence-based
treatment for OA pain. There is a critical need to address the mechanisms for OA pain
due to the aging demographics and the prevalence of OA in older adults. This thesis
project was aimed to study neural mechanisms for OA pain. The general hypothesis was
that the pain of OA arises as a result of phenotypic changes in primary sensory neurons,
especially in larger diameter A-fiber neurons. In vivo intracellular recordings were used
to determine changes in specific populations of DRG neuron in a surgical knee
derangement model of OA in the rat. It was found that AB-fiber low threshold
mechanoreceptors, particularly muscle spindle afferents underwent significant changes
(including changes in action potential configurations and in responses to repetitive
stimulation) one month following the model induction when histopathological changes of
the knee joint and the nocifensive behaviors of the affected lower limb favor OA.
Nociceptors, including C-, As- and AB-fiber neurons remained largely unchanged at one
month OA. AB-fiber high threshold mechanoreceptors exhibited significant changes at
two month OA, a later phase during the progression of OA. The data demonstrate that
distinct populations of dorsal root ganglia neuron are altered during the progression of
OA, which might be the neuronal basis for clinical presentations of sensory deficit in OA including pain and loss of proprioception. The data also suggest that the pain in OA
might be a form of neuropathic pain. </p> / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/19469 |
| Date | 03 1900 |
| Creators | Wu, Qi |
| Contributors | Henry, James L., Medical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
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