UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Pharmacological, Neurochemical and Functional Characterisation of the MIA Model of Experimental Osteoarthritis

Thakur, M; (2012) Pharmacological, Neurochemical and Functional Characterisation of the MIA Model of Experimental Osteoarthritis. Doctoral thesis , UCL (University College London).

Full text not available from this repository.

Abstract

More than 10 million adults consult their GP each year with arthritis and related conditions. Significantly, painful osteoarthritis imposes a much more significant limitation on function than non-­‐painful osteoarthritis. This has lead to a focus on therapies that offer symptomatic relief for sufferers of painful osteoarthritis. Many existing analgesics that are able to partially reduce patients’ pain have undesirable adverse effects when given chronically, especially in elderly patients. Hence the need for greater understanding of the mechanisms involved in osteoarthritis pain, to aid the development of more effective, better-­‐tolerated analgesics. The MIA model of experimental osteoarthritis uses a single intraarticular injection of the metabolic inhibitor monoiodoacetate (MIA) to induce a joint degeneration that closely resembles osteoarthritis. In rats, the model is associated with joint pain that refers to the hindpaw. This PhD thesis presents work characterizing functional plasticity in the MIA model using spinal cord electrophysiology, behavioural pharmacology and immunohistochemistry. The role of spinal and peripheral nerve hyperpolarization-­‐activated cyclic nucleotide gated cation (HCN) channels in osteoarthritis pain was assessed using the HCN channel blocker, ZD7288. These experiments and others using the KCNQ potassium channel blocker XE991, demonstrate novel physiological roles for these ion channels in nociception. Electrophysiology experiments show that the novel analgesic tapentadol, a joint opioid receptor agonist/noradrenaline reuptake inhibitor, is able to reduce nociceptive spinal activity in the MIA model. Lastly, a series of experiments evaluate the biochemically, behaviourally and pharmacologically distinct phenotypes of two variants of the MIA model. The data gathered in this thesis illustrate a number of novel features of this experimental model of osteoarthritis pain, and will inform the development of novel analgesics for osteoarthritis.

Type: Thesis (Doctoral)
Title: Pharmacological, Neurochemical and Functional Characterisation of the MIA Model of Experimental Osteoarthritis
Language: English
Additional information: Permission for digitisation not received
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1353795
Downloads since deposit
1Download
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item