Different effects of spinally applied prostaglandin D2 on responses of dorsal horn neurons with knee input in normal rats and in rats with acute knee inflammation.

Abstract

Prostaglandin D2(PGD2) is the most produced prostanoid in the CNS of mammals, and in behavioral experiments it has been implicated in the modulation of spinal nociception. In the present study we addressed the effects of spinal PGD2 on the discharge properties of nociceptive spinal cord neurons with input from the knee joint using extracellular recordings in vivo, both in normal rats and in rats with acute inflammation in the knee joint. Topical application of PGD2 to the spinal cord of normal rats did not influence responses to mechanical stimulation of the knee and ankle joint except at a high dose. Specific agonists at either the prostaglandin D2 receptor 1 (DP1) or the prostaglandin D2 receptor 2 (DP2) receptor had no effect on responses to mechanical stimulation of the normal knee. By contrast, in rats with inflamed knee joints either PGD2 or a DP1 receptor agonist decreased responses to mechanical stimulation of the inflamed knee and the non-inflamed ankle thus reducing established inflammation-evoked spinal hyperexcitability. Vice versa, spinal application of an antagonist at DP1 receptors increased responses to mechanical stimulation of the inflamed knee joint and the non-inflamed ankle joint suggesting that endogenous PGD2 attenuated central sensitization under inflammatory conditions, through activation of DP1 receptors. Spinal application of a DP2 receptor antagonist had no effect. The conclusion that spinal PGD2 attenuates spinal hyperexcitability under inflammatory conditions is further supported by the finding that spinal coapplication of PGD2 with prostaglandin E2 (PGE2) attenuated the PGE2-induced facilitation of responses to mechanical stimulation of the normal joint.

• Authors: A Telleria-Diaz, A Ebersberger, E Vasquez, F Schache, J Kahlenbach, H-G Schaible
• Journal: Neuroscience (Neuroscience) Vol. 156 Issue 1 Pg. 184-92 (Sep 22 2008) ISSN: 0306-4522 [Print] United States
• PMID: 18678231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Immunologic
• Receptors, Prostaglandin
• Dinoprostone
• Prostaglandin D2
• prostaglandin D2 receptor

Topics

• Action Potentials (drug effects, physiology)
• Acute Disease
• Afferent Pathways (metabolism, physiopathology)
• Animals
• Arthralgia (metabolism, physiopathology)
• Arthritis (metabolism, physiopathology)
• Dinoprostone (metabolism, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hindlimb (innervation, physiopathology)
• Nociceptors (metabolism)
• Physical Stimulation
• Posterior Horn Cells (drug effects, metabolism)
• Prostaglandin D2 (metabolism, pharmacology)
• Rats
• Receptors, Immunologic (agonists, metabolism)
• Receptors, Prostaglandin (agonists, metabolism)
• Tarsus, Animal (innervation, physiopathology)