Inhibitory effect of somatostatin on inflammation and nociception.
The present review focuses on promising new opportunities for anti-inflammatory and analgesic therapy. The theoretical background is an original observation based on our own experimental results. These data demonstrate that somatostatin is released from capsaicin-sensitive, peptidergic sensory nerve endings in response to noxious heat and chemical stimuli such as vanilloids, protons or lipoxygenase products. It reaches distant parts of the body via the circulation and exerts systemic anti-inflammatory and analgesic effects. Somatostatin binds to G-protein-coupled membrane receptors (sst(1)-sst(5)) and diminishes neurogenic inflammation by prejunctional action on sensory-efferent nerve terminals, as well as by postjunctional mechanisms on target cells. It decreases the release of pro-inflammatory neuropeptides from sensory nerve endings and also acts on receptors of vascular endothelial, inflammatory and immune cells. Analgesic effect is mediated by an inhibitory action on peripheral terminals of nociceptive neurons, since circulating somatostatin cannot exert central action. Somatostatin itself is not suitable for drug development because of its broad spectrum and short elimination half life, stable, receptor-selective agonists have been synthesized and investigated. The present overview is aimed at summarizing the physiological importance of somatostatin and sst receptors, pharmacological significance of synthetic agonists and their potential in the development of novel anti-inflammatory and analgesic drugs. These compounds might provide novel perspectives in the pharmacotherapy of acute and chronic painful inflammatory diseases, as well as neuropathic conditions.
Pintér
Erika
E
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7624 Pécs, Szigeti u. 12, Hungary. erika.pinter@aok.pte.hu
Helyes
Zsuzsanna
Z
Szolcsányi
János
J
D000700:Analgesics / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D009479:Neuropeptides / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D017481:Receptors, Somatostatin / Q000187:drug effects*; D012677:Sensation / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology*
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D009479:Neuropeptides; D017481:Receptors, Somatostatin; D013004:Somatostatin