<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)