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Title: A role for prostanoids in spinal nociceptive processing
Author: Willingale, Hilary
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2001
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Increasingly, evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) have central actions within the spinal cord in addition to the peripheral actions that have traditionally been associated with them. NSAIDs are commonly used in pain relief and inhibit cyclooxygenase activity (cox) that converts arachidonic acid to prostaglandins (PGs). This study addressed the hypothesis that prostaglandins within the spinal cord play a role in pain processing. The presence of two isoforms of cox, cox-1 and cox-2, within the spinal cord of rats was identified for the first time using Western blotting techniques. Cox-2, but not cox-1, was shown to be upregulated during the development of an acute arthritis. The active biosynthetic pathway for PG production was therefore shown to be present and active in the spinal cord. Extracellular recordings of wide dynamic range neurons within the lumbar spinal cord were made to study their responses to nociceptive mechanical stimuli in non-arthritic, acutely arthritic and chronically arthritic rats. Intrathecal NSAIDs had no effect on the responses recorded in non-arthritic rats. The responses of hyperexcitable, but not non- hyperexcitable neurons, in arthritic rats were concentration-dependently reduced by intrathecal NSAIDs. Hyperexcitable cells were defined subjectively as those with bursting artivfty and were found in arthritic but not non-arthritic rats. The C-fibre wind- up of a nociceptive spinal reflex, the hindlimb extensor reflex, was dose-dependently reduced by intravenous indomethacin (a NSAID) and a selective cox-2 antagonist, SC58125. Intrathecal indomethacin also concentration-dependently reduced the wind-up. An effect was therefore shown in hyperalgesic (and allied) but not non-hyperalgesic states. A possible model for the role of spinal prostaglandins in the development of hyperalgesia is proposed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available