Elsevier

Neuroscience

Volume 93, Issue 2, July 1999, Pages 775-781
Neuroscience

The intraspinal release of prostaglandin E2 in a model of acute arthritis is accompanied by an up-regulation of cyclo-oxygenase-2 in the spinal cord

https://doi.org/10.1016/S0306-4522(99)00164-5Get rights and content

Abstract

In anaesthetized rats, the intraspinal release of immunoreactive prostaglandin E2 was measured using antibody microprobes. We addressed the question of whether the release of immunoreactive prostaglandin E2 is altered during development of acute inflammation in the knee evoked by intra-articular injections of kaolin and carrageenan. We also examined cyclo-oxygenase-1 and cyclo-oxygenase-2 protein levels in the spinal cord during the development of inflammation using the same model of arthritis. Densitometric analysis of microprobes showed that basal release of immunoreactive prostaglandin E2 in the period 175–310 min after kaolin was slightly higher than in the absence of inflammation. A pronounced enhancement of basal release of immunoreactive prostaglandin E2 was observed 430–530 min after kaolin. Enhanced levels of immunoreactive prostaglandin E2 were observed throughout the dorsal and ventral horns. Release of immunoreactive prostaglandin E2 was not altered further by the application of innocuous and noxious pressure onto the inflamed knee. Western blot analysis revealed that cyclo-oxygenase-2 but not cyclo-oxygenase-1 protein levels were elevated in the spinal cords of animals with inflammation compared to normal animals. This effect was evident as early as 3 h after the induction of arthritis. The maximum elevation of cyclo-oxygenase-2 protein levels (six-fold) was observed 12 h after the induction of arthritis.

The results show that there is a tonic release of immunoreactive prostaglandin E2 from the spinal cord following the induction of arthritis, which is accompanied by enhanced expression of cyclo-oxygenase-2 protein in the spinal cord. We suggest that intraspinal prostaglandins may play a role in inflammation-evoked central sensitizatlon of spinal cord neurons.

Section snippets

Animal preparation

Male Wistar rats (Charles River, Sulzfeld, Germany; 230–400 g) were anaesthetized with sodium thiopentone (initial dose 75–125 mg/kg) for antibody microprobe experiments and with thiobutabarbital (Inactin, Research Biochemical Inc; 100 mg/kg, i.p.) for western blotting experiments. The depth of anaesthesia was assessed by testing for hindlimb withdrawal and corneal reflexes, which had to be absent. Additional anaesthetic was given (i.p.) as required. Cannulae were placed in the trachea, carotid

Basal release

The development of inflammation in the knee joint was associated with an enhancement of IR-PGE2 release in the absence of mechanical stimulation. Figure 1 shows the averaged densitometric analysis of probes inserted either in control animals or in two groups of animals in which an inflammation in the knee joint had been induced before microprobes were used. Figure 1A displays the image of probes that were inserted for periods of 10 min in the spinal cord of four control animals, and the image of

Discussion

The data of the present study show that an inflammation in the joint leads to enhanced intraspinal PGE2 release and an increase in COX-2 protein levels in the spinal cord. Several aspects of the results are noteworthy. (1) The enhanced PGE2 release was mainly observed several hours after induction of inflammation. (2) The pattern of IR-PGE2 release showed that the level of PGE2 was elevated throughout the gray matter of the spinal cord, including the dorsal and ventral horns. (3) Increased

Conclusion

In summary, we have shown that the development of acute inflammation in the knee joint is followed by an increase in the intraspinal release of IR-PGE2 and by an increase of the expression of COX-2 protein in the spinal cord.

Acknowledgements

We thank Mrs T. Hoffmann for technical assistance. The work was supported by the Deutsche Forschungsgemeinschaft (SFB 353) and a British Council Research Collaboration Grant awarded to Dr B. D. Grubb.

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    *

    Present address: Klinikum der Friedrich-Schiller-Universität Jena, Institut für Physiologie, Teichgraben 8, D-07740 Jena, Germany.

    Present address: Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, U.K.

    Present address: Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, U.K.

    Present address: Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, U.K.

    Present address: Rheinische Landes- und Hochschulklinik Essen, Virchowstraße 174, D-45147 Essen, Germany.

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