  Pain remains a major concern in patients suffering from metastatic cancer to
the bone and more knowledge of the condition, as well as novel treatment
avenues, are called for. Neuropeptide Y (NPY) is a highly conserved peptide
that appears to play a central role in nociceptive signaling in inflammatory
and neuropathic pain. However, little is known about the peptide in
cancer-induced bone pain. Here, we evaluate the role of spinal NPY in the
MRMT-1 rat model of cancer-induced bone pain. Our studies revealed an
up-regulation of NPY-immunoreactivity in the dorsal horn of cancer-bearing rats
17 days after inoculation, which could be a compensatory antinociceptive
response. Consistent with this interpretation, intrathecal administration of
NPY to rats with cancer-induced bone pain caused a reduction in nociceptive
behaviors that lasted up to 150 min. This effect was diminished by both Y1
(BIBO3304) and Y2 (BIIE0246) receptor antagonists, indicating that both
receptors participate in mediating the antinociceptive effect of NPY. Y1 and Y2
receptor binding in the spinal cord was unchanged in the cancer state as
compared to sham-operated rats, consistent with the notion that increased NPY
results in a net antinociceptive effect in the MRMT-1 model. In conclusion, the
data indicate that NPY is involved in the spinal nociceptive signaling of
cancer-induced bone pain and could be a new therapeutic target for patients
with this condition.
