Neuroscience
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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. ⋯ 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.
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Intimate structural and functional relationships between gap junctions and adherens junctions have been demonstrated in peripheral tissues, but have not been thoroughly examined in the central nervous system, where adherens junctions are often found in close proximity to neuronal gap junctions. Here, we used immunofluorescence approaches to document the localization of various protein components of adherens junctions in relation to those that we have previously reported to occur at electrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36). The adherens junction constituents N-cadherin and nectin-1 were frequently found to localize near or overlap with Cx36-containing gap junctions in several brain regions examined. ⋯ The deployment of the protein constituents of these junctions was especially striking at somatic contacts between primary afferent neurons in the mesencephalic trigeminal nucleus (MesV), where the structural components of adherens junctions appeared to be maintained in connexin36 null mice. These results support emerging views concerning the multi-molecular composition of electrical synapses and raise possibilities for various structural and functional protein-protein interactions at what now can be considered the adherens junction-neuronal gap junction complex. Further, the results point to intracellular signaling pathways that could potentially contribute to the assembly, maintenance and turnover of this complex, as well as to the dynamic nature of neuronal communication at electrical synapses.