Nociceptive behavior induced by the endogenous opioid peptides dynorphins in uninjured mice: evidence with intrathecal N-ethylmaleimide inhibiting dynorphin degradation
2009 (English)In: Advances in neuropharmacology / [ed] Bagetta G; Corasaniti MT; Sakurada T; Sakurada S, San Diego: Elsevier Academic Press , 2009, Vol. 85, 191-205 p.Chapter in book (Refereed)
Dynorphins, the endogenous opioid peptides derived from prodynorphin may participate not only in the inhibition, but also in facilitation of spinal nociceptive transmission. However, the mechanism of pronociceptive dynorphin actions, and the comparative potential of prodynorphin processing products to induce these actions were not fully elucidated. In our studies, we examined pronociceptive effects of prodynorphin fragments dynorphins A and B and big dynorphin consisting of dynorphins A and B, and focused on the mechanisms underlying these effects. Our principal finding was that big dynorphin was the most potent pronociceptive dynorphin; when administered intrathecally into mice at extremely low doses (1-10fmol), big dynorphin produced nociceptive behavior through the activation of the NMDA receptor ion-channel complex by acting on the polyamine recognition site. We next examined whether the endogenous dynorphins participate in the spinal nociceptive transmission using N-ethylmaleimide (NEM) that blocks dynorphin degradation by inhibiting cysteine proteases. Similar to big dynorphin and dynorphin A, NEM produced nociceptive behavior mediated through inhibition of the degradation of endogenous dynorphins, presumably big dynorphin that in turn activates the NMDA receptor ion-channel complex by acting on the polyamine recognition site. Our findings support the notion that endogenous dynorphins are critical neurochemical mediators of spinal nociceptive transmission in uninjured animals. This chapter will review above-described phenomena and their mechanism.
Place, publisher, year, edition, pages
San Diego: Elsevier Academic Press , 2009. Vol. 85, 191-205 p.
, International Review of Neurobiology, ISSN 0074-7742 ; 85
IdentifiersURN: urn:nbn:se:uu:diva-120095DOI: 10.1016/S0074-7742(09)85015-0ISI: 000268886500015PubMedID: 19607971ISBN: 978-0-12-374893-5OAI: oai:DiVA.org:uu-120095DiVA: diva2:302477