부산대학교 도서관

1 The administration of κ-opioid receptor antagonists, nor-binaltorphimine (norBNl) and 5′-guanidSiionallrindole (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 κ-opioid receptor dynorphin. 2 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 norBNl. GNTI (κ-opioid receptor antagonists), dynorphin A[sub1-17] antiserum (DYN A/S). ketamine (NMDA receptor antagonist) and their combinations. The noeiceptive sensitivity was assessed using the mechanical (von Frey) and thermal allodynia tests on days 2-4 and 8- 10 after the sciatic nerve ligation. 3 Both antagonists, norBNl and GNT1, significantly enhanced mechanical and thermal allodynia in rats and mice with neuropathic pain. The potenliation of allodynia alter the administration of norBNl or GNTI was inhibited by earlier administration of DYN A/S or by ketamine. 4 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 κ-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. [ABSTRACT FROM AUTHOR]