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
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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Cited by (116)
5.32 - Joint Pain
2020, The Senses: A Comprehensive Reference: Volume 1-7, Second EditionVariability in analgesic response to non-steroidal anti-inflammatory drugs
2018, Prostaglandins and Other Lipid MediatorsAntinociceptive effects of buprenorphine in zebrafish larvae: An alternative for rodent models to study pain and nociception?
2014, Applied Animal Behaviour ScienceEtifoxine analgesia in experimental monoarthritis: A combined action that protects spinal inhibition and limits central inflammatory processes
2014, PainCitation Excerpt :For example, neutralization of tumor necrosis factor α (TNFα), directly at the joint or in the spinal cord of monoarthritic rats, produces significant antinociception [4,5]. Increased prostaglandin E2 (PGE2) synthesis and release has been demonstrated clearly in the spinal cord of rats suffering from monoarthritic pain [51] as a result of overexpression of the inducible PGE2-synthesizing enzyme cyclooxygenase type 2 [16]. Agreeing with these findings is research showing that intrathecal application of PGE2 produces significant excitation of spinal cord neurons in naive rats [49], and increases pain symptoms when injected in vivo [29,30,48].
Prostanoids and inflammatory pain
2013, Prostaglandins and Other Lipid MediatorsCitation Excerpt :Numerous studies showed a marked release of spinal PGE2 after inflammatory and nociceptive stimulation. For example, increased spinal PGE2 release contributed to inflammation-evoked central sensitization in the carrageenan-induced acute arthritis model [70] and the CFA- or zymosan-induced chronic hindpaw inflammation models [33,71]. Similarly, injection of formalin into the hind paw evoked a biphasic spinal release of PGE2 which corresponded to the formalin-induced biphasic flinching of the injured paw [72].
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Present address: Klinikum der Friedrich-Schiller-Universität Jena, Institut für Physiologie, Teichgraben 8, D-07740 Jena, Germany.
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Present address: Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, U.K.
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Present address: Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, U.K.
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Present address: Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, U.K.
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Present address: Rheinische Landes- und Hochschulklinik Essen, Virchowstraße 174, D-45147 Essen, Germany.