Neuropeptide Y is Up-regulated and Induces Antinociception in Cancer-induced Bone Pain

Abstract

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.

Decitabine attenuates nociceptive behavior in a murine model of bone cancer pain

“…Acute administration of naloxone methiodide led to a subtle increase in movement-evoked nociception but not weight-bearing induced nociception. Our result is supported by previous work that demonstrated that the limb use test is more sensitive than the weight-bearing test for the measurement of nociception in animal models of bone cancer pain [14,22,23]. Another explanation may be that the two tests measure different components of cancer-induced bone pain mediated by different mechanisms with different opioid sensitivity [25].…”

Dysregulated Tear Fluid Nociception-Associated Factors, Corneal Dendritic Cell Density, and Vitamin D Levels in Evaporative Dry Eye

“…51 NPY is a peptide known for its central role in antinociceptive signaling during inflammatory and neuropathic pain. 52,53 Hence, in the current study it is apparent that there is an imbalance in nociceptive factors favoring ocular surface discomfort in patients of DED. Regaining nociceptive factor balance in the DED patients may therefore be beneficial in reducing symptoms suggesting a role for targeted immunomodulatory or biologic therapies.…”

Identification of key candidate genes in neuropathic pain by integrated bioinformatic analysis

“…We found that some of these genes that were involved in the progression of NP have been reported in recent years. For example, accumulating evidence has shown that Npy is involved in the pathogenesis of NP via mediating antinociceptive actions in DRG neurons of the spinal cord . As we know, Npy is a highly conserved endogenous peptide in all mammalian central and peripheral nervous systems and is important in both pro‐ and anti‐nociceptive effects …”