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Title: Behavioural and neuronal correlates of central pain processing in a rat model of osteoarthritis
Author: Montagut-Bordas, Carlota
ISNI:       0000 0004 8507 6281
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Osteoarthritis (OA) of the knee join is a chronic condition characterized by the loss of articular cartilage around the joint leading to changes in joint capsule. Clinically, OA is manifested by joint stiffness, swelling, bone tenderness, discomfort upon movement and joint pain. The latter is the main reason why patients seek medical treatment. OA pain is often classified as nociceptive due to tissue damage leading to inflammation. However, a subgroup of OA patients exhibits pain with neuropathic pain-like features. Thus, it is important to understand the differences in pain processing between these two groups of patients, as it will have implications on treatment. 2mg of monosodium iodoacetate (MIA) was intra-articularly injected into the left knee of male Sprague-Dawley rats in order to study behavioural and electrophysiological changes that appear during the development of OA pain. The MIA model provides two distinct stages of OA pain. An early acute inflammatory stage (2-4 days after MIA injection) and a late stage that presents neuropathic pain-like features (14-21 days post MIA injection). Cartilage damage scores differ between the early and late stage MIA animals with the latter exhibiting a more severe maximal OA score. Behaviourally, paw withdrawal thresholds decrease in the acute inflammatory stage and returned almost back to baseline in the late stage. Weight bearing deficits are present in both stages suggesting that both groups exhibit on going pain. CaV2.2 is present in the pre-synaptic terminals of primary afferent fibers in the spinal dorsal horn and mediates neurotransmitter release. ω-conotoxin GVIA is a small peptide that acts as a state independent blocker of CaV2.2, while TROX-1 is a state dependent blocker of the channel. In-vivo electrophysiological recordings of WDR neurones revealed that ω-conotoxin was able to significantly inhibit neuronal evoked responses to electrical, dynamic brush, mechanical and thermal stimuli in the late stage MIA animals but had little or no effects in the early stage MIA animals. State dependent blocker TROX-1, had no effects in neuronal responses of WDR neurones, in any group. Additionally, in-vivo electrophysiological revealed an increased descending serotonergic drive in a subgroup of late stage MIA animals. Additionally, Descending noxious inhibitory controls (DNIC) disappeared in this stage of the model as observed after neuropathy. Suggesting that in the late stage descending modulation is altered.
Supervisor: Dickenson, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available