HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Antagonists of the kappa-opioid receptor enhance allodynia in rats and mice after sciatic nerve ligation.

Abstract
The administration of kappa-opioid receptor antagonists, nor-binaltorphimine (norBNI) and 5'-guanidinonaltrindole (GNTI) enhanced allodynia in rats and mice after sciatic nerve ligation. In order to understand the mechanism underlying this effect, we examined the possible involvement of the endogenous ligand of kappa-opioid receptor dynorphin. The experiments were carried out on male Wistar rats and on Albino-Swiss mice. The rats had been implanted with a catheter 7 days earlier in the subarachnoid space of the spinal cord. Intrathecal (i.t.) administrations in mice were made by lumbar puncture. The animals were i.t. injected with norBNI, GNTI (kappa-opioid receptor antagonists), dynorphin A1-17 antiserum (DYN A/S), ketamine (NMDA receptor antagonist) and their combinations. The nociceptive sensitivity was assessed using the mechanical (von Frey) and thermal allodynia tests on days 2-4 and 8-10 after the sciatic nerve ligation. Both antagonists, norBNI and GNTI, significantly enhanced mechanical and thermal allodynia in rats and mice with neuropathic pain. The potentiation of allodynia after the administration of norBNI or GNTI was inhibited by earlier administration of DYN A/S or by ketamine. Our results suggest that allodynia is mediated through nonopioid effect of the endogenous opioid peptide, dynorphin. The nonopioid action is potentiated by the blockade of kappa-opioid receptors, and corresponding to the elevation of prodynorphin mRNA level in neuropathic pain. Furthermore, the potentiation of allodynia after the administration of the above drugs appears to be mediated through the activation of NMDA receptors directly by dynorphin.
AuthorsI Obara, J Mika, M K-H Schafer, B Przewlocka
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 140 Issue 3 Pg. 538-46 (Oct 2003) ISSN: 0007-1188 [Print] England
PMID12970097 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Narcotic Antagonists
  • Receptors, Opioid, kappa
Topics
  • Animals
  • Ligation
  • Male
  • Mice
  • Narcotic Antagonists (pharmacology)
  • Pain (metabolism)
  • Pain Measurement (drug effects, methods)
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, kappa (antagonists & inhibitors, biosynthesis)
  • Sciatic Nerve (metabolism, physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: