к Opioids inhibit tumor angiogenesis by suppressing VEGF signaling.

Opioids are effective analgesics for the management of moderate to severe cancer pain. Here we show that κ opioid receptor (KOR) agonists act as anti-angiogenic factors in tumors. Treatment with KOR agonists, U50,488H and TRK820, significantly inhibited human umbilical vein endothelial cell (HUVEC) migration and tube formation by suppressing VEGFR2 expression.

Sensation of abdominal pain induced by peritoneal carcinomatosis is accompanied by changes in the expression of substance P and μ-opioid receptors in the spinal cord of mice.

Background: Patients with peritoneal carcinomatosis often report abdominal pain, which is relatively refractory to morphine. It has been considered that a new animal model is required to investigate the mechanism of abdominal pain for the development of optimal treatments for this type of pain.

Methods: To prepare a peritoneal carcinomatosis model, highly peritoneal-seeding gastric cancer cells, 60As6, were implanted into the abdominal cavity.

Subdiaphragmatic vagotomy induces a functional change in visceral Aδ primary afferent fibers in rats.

Vagal nerves modulate not only physical homeostasis, but also pain transmission. It has been reported that subdiaphragmatic vagal dysfunction causes visceral pain. However, the functional changes in nociceptive primary afferent fibers under such visceral pain soon after subdiaphragmatic vagal dysfunction are not fully documented.

Subdiaphragmatic vagotomy increases the sensitivity of lumbar Aδ primary afferent neurons along with voltage-dependent potassium channels in rats.

Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats.

Upregulation of bradykinin receptors is implicated in the pain associated with caerulein-induced acute pancreatitis.

Although the way for pain management associated with acute pancreatitis has been searched for, there are not enough medications available for it. The aim of the present study was to investigate the role of bradykinin (BK) in pain related to acute pancreatitis. After repeated injections of caerulein (50 μg/kg and 6 times), mice showed edema in the pancreas, and blood concentrations of pancreatic enzymes (amylase and lipase) were clearly elevated.

The κ opioid system regulates endothelial cell differentiation and pathfinding in vascular development.

The opioid system (opioid peptides and receptors) regulates a variety of neurophysiologic functions, including pain control. Here we show novel roles of the κ opioid system in vascular development. Previously, we revealed that cAMP/protein kinase A (PKA) signaling enhanced differentiation of vascular progenitors expressing VEGF receptor-2 (fetal liver kinase 1; Flk1) into endothelial cells (ECs) through dual up-regulation of Flk1 and Neuropilin1 (NRP1), which form a selective and sensitive VEGF(164) receptor.

KP-102 (growth hormone-releasing peptide-2) attenuates ischemia/reperfusion injury in isolated rat hearts.

KP-102, a synthetic growth hormone (GH)-releasing peptide, exerts a variety of effects on cardiac function. In the present study, we investigated the direct cardiac effects of KP-102 with regard to ischemia/reperfusion injury by using isolated rat hearts. Isolated Wistar rat hearts were mounted on a Langendorff apparatus and subjected to 30 min of ischemia followed by 40 min of reperfusion.

General pharmacology of KP-102 (GHRP-2), a potent growth hormone-releasing peptide.

The general pharmacological effects of the hexapeptide KP-102 (D-alanyl-3-(2-naphthyl)-D-alanyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide dihydrochloride, growth hormone-releasing peptide-2, GHRP-2, pralmorelin, CAS 158861-67-7), which potently promotes growth hormone (GH) release by acting at both hypothalamic and pituitary sites, were evaluated in various animal experimental models. The administration of KP-102 showed no obvious effect at a pharmacological dose on the central nervous system. KP-102 had no significant effect on the autonomic nervous system and smooth muscle except a slight and transient increase in spontaneous motility of isolated rabbit ileum and contraction of isolated guinea pig ileum at high doses.