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Purpose Opioid-induced spastic paraplegia after transient spinal cord ischemia during aortic surgery has been reported. Opioids modulate neurotransmission through mu (l) opioid receptors (MORs) in the spinal ventral horn. However, their effects during ischemic insult are not understood. Methods The effects of the selective μ agonist [D-[Ala.sup.2], N-Me-[Phe.sup.4], [Gly.sup.5]-ol]enkephalin (DAMGO) on ischemia-induced agonal currents were examined in the spinal lamina IX neurons of neonatal rats by using the whole-cell patch-clamp technique. Ischemia was simulated in vitro by oxygen/glucose deprivation. Results DAMGO (1 µM) produced outward currents in ~60% of spinal lamina IX neurons at a holding potential of -70 mV. Superfusion with ischemia-simulating medium elicited an agonal current. The latency was 457 [+ or -] 18 s. Despite its neuromodulatory effects, DAMGO did not significantly change the latencies of the agonal currents with (440 ± 23 s) or without (454 ± 33 s) DAMGO-induced currents. Conclusion Activation of MORs does not influence ongoing ischemia-induced neuronal death. Our findings indicate that MOR agonist administration should be suitable as an anesthetic during aortic surgery. Keywords μ Opioid * Oxygen and glucose deprivation * Spinal cord ischemia * Spinal motoneuron, Introduction One of the most worrisome complications of thoracoabdominal aneurysm repair is paraplegia caused by spinal cord ischemia because it results in serious physical disability [1]. Because the extent of [...]

Purpose Pruritus associated with intrathecal opioid administration is a common side effect. There is evidence that κ-opioid receptor agonists have antipruritic activity. Butorphanol has agonist actions at both κ-opioid and μ-opioid receptors. This study was designed to evaluate the antipruritic efficacy of butorphanol after intrathecal morphine administration in the setting of a randomized, double-blind study of parturients undergoing cesarean section. Methods Ninety-one women who received combined spinal-epidural anesthesia with 1.2 ml 0.5 % isobaric bupivacaine and 0.1 mg preservative-free morphine were included in this study. After delivery of the baby, the parturients were randomly allocated to two groups: butorphanol group (n = 46) and physiological saline group (n = 45). In the butorphanol group, parturients received an intravenous loading dose of 1 mg butorphanol followed by infusion of 0.2 mg/h butorphanol. The physiological saline group received an infusion of the same volume of physiological saline. The presence of pruritus, visual analog scores for pain, sedation scores, and adverse effects were recorded 1, 2, 4, 6, 8, 10, 12, and 24 h after intrathecal morphine administration. Results The incidence of pruritus at 24 h was significantly more frequent in the physiological saline group than in the butorphanol group (48.9 vs. 13.0 %, P < 0.001). The severity of pruritus was significantly greater in the saline group than in the butorphanol group 2, 4, 6, 8 and 10 h after intrathecal morphine injection (P = 0.004, 0.001, 0.002, and 0.003, respectively). The visual analog scale scores at 24 h were significantly lower in the butorphanol group than in physiological saline group (P < 0.001). The Ramsay sedation score in the butorphanol group was significantly higher than that in the physiological saline group after 1, 2, 4, 6, 8, 10, 12, and 24 h (P < 0.05). There were no significant differences between the two groups in nausea/vomiting and other adverse effects. Conclusion Administration of intravenous butorphanol after delivery of the baby can reduce pruritus that has been induced by intrathecal morphine administration in cesarean delivery with combined spinal-epidural anesthesia. Keywords Pruritus * Intrathecal opioid administration * κ-Opioid receptor, Introduction Intraspinal administration of opioids is one the most effective analgesic methods in many surgical procedures. However, intrathecal opioid injections are often accompanied by many troublesome adverse reactions, e.g., nausea, [...]

Byline: Dickson Carvalho (1), Fabricia Petronilho (1), Francieli Vuolo (1), Roberta Albino Machado (1), Larissa Constantino (1), Remo Guerrini (2), Girolamo Calo (3), Elaine Cristina Gavioli (4), Emilio Luiz Streck (1), Felipe Dal-Pizzol (1) Keywords: Sepsis; Neutrophil migration; NOP receptor; UFP-101; Nociceptin/orphanin FQ Abstract: Objective The aim of this study was investigate the effects of nociceptin/orphanin FQ (N/OFQ) and ([Nphe.sup.1,Arg.sup.14,Lys.sup.15]N/OFQ--NH.sub.2) (UFP-101), the endogenous N/OFQ peptide receptor (NOP) ligand and a selective NOP antagonist, respectively, in the inflammatory response after cecal ligation and puncture (CLP) model of sepsis in rats. Design Prospective, controlled experiment. Setting Animal basic science laboratory. Subjects Male Wistar rats, weighing 300--350 g. Interventions Rats subjected to CLP were treated with N/OFQ (0.001, 0.01 or 0.1 mg/kg) or UFP-101 (0.03, 0.03 or 0.3 mg/kg) subcutaneously administered immediately after surgery. Measurements and main results Twelve hours after surgery, blood was collected by cardiac puncture and bronchoalveolar (BAL) and peritoneal lavage were performed. In a separate set of experiments mortality was evaluated monitoring CLP rats for 10 days. Our findings showed that UFP-101 (0.03 mg/kg, sc, but not 0.003 mg/kg) modified parameters related to the systemic inflammatory response by effectively preventing cells migration, bacterial dissemination, and by modulating the release of pro-inflammatory cytokines and chemokines, and reducing animal mortality in a clinically relevant model of sepsis. By contrast, N/OFQ (0.1 mg/kg, sc) increased mortality in the CLP model. Conclusions Our findings point to a functional relationship between the N/OFQ-NOP receptor system and inflammatory response in the CLP model of sepsis and suggest that NOP receptor antagonists are worthy of testing as innovative drugs for the treatment of sepsis. Author Affiliation: (1) Laboratorio de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Avenida Universitaria, 1105, Criciuma, SC, 88806-000, Brazil (2) Department of Pharmaceutical Science and Biotechnology Center, University of Ferrara, Ferrara, Italy (3) Department of Experimental and Clinical Medicine, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy (4) Laboratorio de Neurociencias, Universidade do Extremo Sul Catarinense, Criciuma, SC, Brazil Article History: Registration Date: 30/09/2008 Received Date: 04/01/2008 Accepted Date: 28/09/2008 Online Date: 10/10/2008

Abstract: Experiments were performed on mongrel male rats to study the effects of blockade of [delta], u, and Io opiate receptors on antibody formation, delayed-type hypersensitivity (DTH), and changes in the numbers of antibody-forming cells (AFC) and nucleated cells in the lymph nodes and spleen in a local form of immune response in a model of rotation stress. These studies showed that rotation stress led to mild suppression of immune inflammation in DTH, significant increases in the numbers of AFC and nucleated cells in regional lymph nodes, but no change in the peripheral blood antibody titer. Blockade of [delta], u, and Io opiate receptors with naloxone altered these stress-induced effects. It is suggested that abolition of the stimulating effect of rotation stress on the number of AFC and depression of DTH may be associated with blockade of the effects of [beta]-endorphin and met-enkephalin, which act predominantly via stimulation of [delta] receptors. Article History: Registration Date: 29/12/2004

Byline: L. V. Devoino (1), M. A. Cheido (1), E. L. Al'perina (1) Keywords: DAGO; opioid u receptor agonist; immunostimulation; nucleus accumbens; dopaminergic system Abstract: The involvement of the nucleus accumbens in neuroimmunostimulation was demonstrated during activation of opioid u receptors with the selective agonist DAGO (100 ug/kg) single doses of this agent to sham-operated (control) Wistar rats induced significant increases in the numbers of direct IgM antibody-forming and total rosette-forming cells after immunization with sheep erythrocytes. Bilateral electrolytic lesioning of the nucleus accumbens in rats led to sharp decreases in the intensity of immune responses there was no immunostimulation after administration of DAGO to these animals. These data provide evidence for the involvement of the nucleus accumbens in the process of immunomodulation and for the importance of opioid u receptors in the nucleus accumbens in the stimulation of immunogenesis. Author Affiliation: (1) State Science Research Institute of Physiology, Siberian Division, Russian Academy of Medical Sciences, 4 Timakov Street, 630117, Novosibirsk, Russia Article History: Registration Date: 09/10/2004