Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Pronociceptive role of dynorphins in uninjured animals: N-ethylmaleimide-induced nociceptive behavior mediated through inhibition of dynorphin degradation

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Tan-No, K.
  • Takahashi, H.
  • Nakagawasai, O.
  • Niijima, F.
  • Sato, T.
  • Satoh, S.
  • Sakurada, S.
  • Marinova, Z.
  • Yakovleva, T.
  • Bakalkin, G.
  • Terenius, Lars
  • Tadano, T.

publication date

  • February 2005

journal

  • Pain  Journal

abstract

  • Intrathecal (i.t.) administration into mice of N-ethylmaleimide (NEM), a cysteine protease inhibitor, produced a characteristic behavioral response, the biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank. The behavior induced by NEM was inhibited by the intraperitoneal injection of morphine. We have recently reported that dynorphin A and, more potently big dynorphin, consisting of dynorphins A and B, produce the same type of nociceptive response whereas dynorphin B does not [Tan-No K, Esashi A, Nakagawasai O, Niijima F, Tadano T, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Kisara K. Intrathecally administered big dynorphin, a prodynorphin-derived peptide, produces nociceptive behavior through an N-methyl-d-aspartate receptor mechanism. Brain Res 2002;952:7-14]. The NEM-induced nociceptive behavior was inhibited by pretreatment with dynorphin A- or dynorphin B-antiserum and each antiserum also reduced the nociceptive effects of i.t.-injected synthetic big dynorphin. The characteristic NEM-evoked response was not observed in prodynorphin knockout mice. Naloxone, an opioid receptor antagonist, had no effects on the NEM-induced behavior. Ifenprodil, arcaine and agmatine, antagonists at the polyamine recognition site on the N-methyl-D-aspartate (NMDA) receptor ion-channel complex, and MK-801, an NMDA ion-channel blocker inhibited the NEM-induced effects. Ro25-6981, an antagonist of the NMDA receptor subtype containing NR2B subunit was not active. NEM completely inhibited degradation of dynorphin A by soluble and particulate fractions of mouse spinal cord. Collectively, the results demonstrate that endogenous prodynorphin-derived peptides are pronociceptive in uninjured animals, and required for the NEM-induced behavior. The NEM effects may be 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.

subject areas

  • Agmatine
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Biguanides
  • Dizocilpine Maleate
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Dynorphins
  • Enkephalins
  • Enzyme Inhibitors
  • Ethylmaleimide
  • Excitatory Amino Acid Antagonists
  • Immune Sera
  • Injections, Spinal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphine
  • Narcotics
  • Piperidines
  • Protein Precursors
  • Receptors, Opioid
  • Spinal Cord
  • Time Factors
scroll to property group menus

Research

keywords

  • N-ethylmaleimide
  • N-methyl-D-aspartate receptor ion-channel complex
  • dynorphins
  • intrathecal administration
  • nociceptive behavior
  • prodynorphin knockout mice
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0304-3959

Digital Object Identifier (DOI)

  • 10.1016/j.pain.2004.11.004

PubMed ID

  • 15661437
scroll to property group menus

Additional Document Info

start page

  • 301

end page

  • 309

volume

  • 113

issue

  • 3

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support