Prostaglandin-induced neuropeptide release from spinal cord.
The studies reviewed in this chapter present a convincing argument that prostaglandins have direct actions at the level of the spinal cord to enhance nociception. Furthermore, an increasing body of evidence supports the hypothesis that one important site of action of these eicosanoids is the terminals of sensory neurons. Studies performed in our laboratory add to this evidence by demonstrating that relatively large concentrations of prostaglandins increase SP release, whereas lower amounts augment the capsaicin-stimulated release of both SP and CGRP from rat spinal cord slices. In neuronal cultures of rat dorsal root ganglia, prostaglandins also facilitate the evoked release of SP and CGRP, indicating a direct action of these autocoids on sensory neurons. Based on these studies, it is interesting to speculate that the actions of prostaglandins on peptide release are one mechanism to account for hyperalgesia produced by these eicosanoids. In addition, by a sustained action, prostaglandins may contribute to the enhanced excitability of sensory neurons during inflammation. Indeed, our observations that intrathecal Ketorolac abolished the elevation in SP release during inflammation support this possibility. Whether the effect of the NSAID are caused by the inhibition of prostaglandin synthesis in the spinal cord are yet to be determined. Further work is necessary to establish a role for prostaglandins in the adaptive changes of nociceptive neurons that occur in chronic pain states and in inflammation. In addition, the cellular mechanisms underlying the effects of prostaglandins on sensory neurons are yet to be elucidated.
Vasko
M R
MR
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202-5120, USA.
D000818:Animals; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D011453:Prostaglandins / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*
D009479:Neuropeptides; D011453:Prostaglandins