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.