U532159.pdf (12.42 MB)
The involvement of the cyclooxygenase pathway in spinal nociceptive processing
thesisposted on 2014-12-15, 10:35 authored by Natalie Jane. Gardiner
In recent years evidence has accumulated which suggests that prostaglandins are involved in spinal nociceptive processing. Several studies have shown that spinally-administered prostaglandins evoke characteristic pain behaviour in rats. Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, inhibit the enzyme cyclooxygenase (COX) and thus prevent the formation of prostaglandins. It has been hypothesised that a component of the analgesic properties of NSAIDs may be due to an action in the spinal cord, a theory which is supported by behavioural and electrophysiological studies. The current study shows by Western blotting that the two isoforms of COX, COX-1 and COX-2, are present in rat spinal cord tissue. Furthermore, using immunocytochemical techniques, we have localised COX-2-like immunoreactivity to regions of the spinal cord associated with nociceptive processing, namely the superficial and deep dorsal horn and around the central canal. Spinal COX-2, but not COX-1 is bilaterally upregulated in a time-dependent manner (< 3 days) following the induction of a unilateral inflammation around the ankle joint. An increase in spinal PGE2 levels occurs over the same time course. The basal release of 4 species of prostaglandins was assessed by superfusing the spinal cord with artificial cerebrospinal fluid and analysing the superfusate by radioimmunoassay (PGD2> PGE2> 6-keto-PGF1> PGF2). Using this superfusion technique and an antibody-microprobe technique we detected increases in the spinal release of PGE2 within 30 minutes following acute inflammation. The increased release of PGE2 was maintained for at least 12 hours. Noxious mechanical stimulation also evoked the spinal release of PGE2. In conclusion, we have shown that COX-2 is present in the spinal cord in locations commensurate with an involvement in nociceptive processing. The increase in spinal COX-2 and PGE2 following inflammation suggests that prostaglandins (possibly synthesised by COX-2) may play an active role in modulating spinal nociceptive processing.
Date of award1998-01-01
Author affiliationCell Physiology and Pharmacology
Awarding institutionUniversity of Leicester