Effects of postoperative analgesia with the combination of tramadol and lornoxicam on serum inflammatory cytokines in patients with gastric cancer.

OBJECTIVE: To compare the effects of postoperative patient-controlled intravenous analgesia (PCIA) with morphine, tramadol, or tramadol combined with lornoxicam on serum inflammatory cytokine production. METHODS: 60 patients with an American Society of Anesthesiologists (ASA) physical status of I or II, undergoing radical correction of gastric cancer, were equally randomized to receive PCIA with morphine (M group), tramadol (T group), or tramadol combined with lornoxicam (L group). The visual analog scale (VAS) and Bruggemann comfort scale (BCS) scores were used to evaluate the postoperative analgesic efficacy. Serum levels of the interleukins (IL) IL-2, IL-6, and IL-10, and soluble IL-2 receptor (sIL-2R) were measured before anesthesia, 90 min after incision, and 24, 48, and 72 h after surgery. RESULTS: No significant difference was found in the VAS, BCS, or baseline serum IL-2, IL-6, IL-10, or sIL-2R between the groups. At 90 min after incision, only the IL-6 levels increased (p < 0.05). At 24 h after surgery, the IL-2 levels decreased, with the M group having the lowest levels, while IL-6, IL-10, and sIL-2R levels increased, with the M group having the highest level and the L group having the lowest level (p < 0.05). At 48 h after surgery, the cytokine levels were starting to return to the baselines but still had statistical significance (p < 0.05). At 72 h after surgery, only the IL-6 levels had returned to their baseline. CONCLUSION: PCIA using tramadol combined with lornoxicam has less influence on inflammatory cytokines than morphine or tramadol alone in patients undergoing gastric cancer surgery.

Flurbiprofen improves dysfunction of T-lymphocyte subsets and natural killer cells in cancer patients receiving post-operative morphine analgesia.

OBJECTIVE: Acute pain can lead to immune dysfunction, which can be partly ameliorated by successful pain management. Opioids, which are widely used for analgesia, can result in the deterioration of immune function. This study aimed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery. METHODS: 60 patients undergoing gastric cancer surgery were equally randomized into two groups. They received post-operative patient-controlled intravenous (IV) analgesia using morphine either with or without flurbiprofen. Visual analogue scale (VAS) scores, Bruggemann comfort scale (BCS) scores, morphine consumption, time of first flatus, incidence of nausea/vomiting, and T-lymphocyte subsets (CD3⁺, CD4⁺, and CD8⁺) and natural killer cells (CD3⁻CD16⁺CD56⁺) were evaluated. RESULTS: No significant difference was observed in the VAS scores, BCS scores, and nausea/vomiting incidence between groups. Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone. The expression of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and CD3⁻CD16⁺CD56⁺ decreased at 2 hours after incision and, except for CD3⁻CD16⁺CD56⁺, returned to baseline at 120 hours after surgery. Moreover, the expression of CD3⁻CD16⁺CD56⁺ at 2 hours after incision and the expression of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and CD3⁻CD16⁺CD56⁺ at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone. CONCLUSION: The combination of morphine and flurbiprofen ameliorates the immune depression in Tlymphocyte subsets and natural killer cells and provides a similar analgesic efficacy to morphine alone in patients undergoing gastric cancer surgery.

Blood pressure reduction induced by low dose of epinephrine via different routes in rats.

BACKGROUND: Epinephrine was recently shown to induce a hypotension episode. Activation of ß2-adrenoceptors with smooth muscle relaxation may be the underlying mechanism. This study investigated the effects of ICI 118551, a ß2-adrenoceptors antagonist, on epinephrine-induced blood pressure reduction via different administration routes in rats. METHODS: A total of 144 Sprague Dawley rats were equally randomized into 3 groups (intranasal, intravenous, and intra-arterial administration), each with 4 subgroups: saline + saline, ICI 118551 + saline, saline + epinephrine, and ICI 118551 + epinephrine. All rats were anesthetized while spontaneously breathing. Epinephrine was administered at doses of 5 µg/kg via nose, 0.25 µg/kg via femoral vein, and 0.1 µg/kg via aorta. Mean arterial pressure and heart rate were monitored. RESULTS: Mean arterial pressure decreased in all 3 saline + epinephrine subgroups after administration (P < 0.05), whereas it did not in other subgroups. Heart rate had no significant change in all subgroups. CONCLUSIONS: Epinephrine-induced blood pressure reduction can be prevented by ICI 118551 in rats, suggesting that the activation of ß2-adrenoceptors contributes to blood pressure reduction.

Effects of preemptive intravenous lornoxicam on the analgesic efficacy of epidural morphine and expression of chemokines in women undergoing hysterectomy.

BACKGROUND: It is believed that preemptive IV lornoxicam treatment can reduce the consumption of other analgesics, improve analgesic efficacy, and ameliorate immune function during patient-controlled IV analgesia. However, the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of patient-controlled epidural analgesia (PCEA) with morphine and on chemokine expression remain unknown. OBJECTIVE: The aim of this prospective, randomized, controlled study was to observe the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of PCEA with morphine and on the expression of monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1α (SDF-1α) in women undergoing hysterectomy. METHODS: Patients undergoing elective hysterectomy with combined spinal and epidural anesthesia were randomized to 1 of 3 groups to receive IV lornoxicam 8 mg before anesthesia (group 1), lornoxicam 16-mg injection before anesthesia (group 2), or isotonic saline (control) before anesthesia. PCEA was used to treat postoperative pain, and a visual analog scale (VAS) and the Bruggemann Comfort Scale (BCS) were used to evaluate analgesic efficacy. Morphine consumption was recorded. To measure plasma concentrations of MCP-1 and SDF-1α via enzyme-linked immunosorbent assay, venous blood samples were obtained from patients at 4 separate times: before anesthesia (baseline); 0 (immediately after anesthesia administration); and 24 and 48 hours after surgery. RESULTS: Forty-five patients (mean [SD] age, 41 [5] years; mean [SD] weight, 54 [6] kg) undergoing elective hysterectomy were included in the study. There were no significant differences in VAS scores, BCS scores, or morphine consumption between the 3 groups. Compared with baseline values, MCP-1 and SDF-1α concentrations were increased significantly immediately after surgery in all 3 groups (all, P < 0.01) and returned to near-baseline values at 24 hours postsurgery in groups 1 and 2, and by 48 hours postsurgery in the control group. MCP-1 and SDF-1α concentrations in groups 1 and 2 were significantly lower than those in the control group immediately (all, P < 0.01) and 24 hours postsurgery (all, P < 0.05). CONCLUSION: Preemptive IV lornoxicam treatment was associated with attenuation of the plasma concentrations of MCP-1 and SDF-1α immediately after and 24 hours after hysterectomy and was associated with more rapid resolution to near-baseline concentrations of both cytokines in these patients compared with controls; however, it was not associated with significantly reducing epidural morphine consumption.

Repeated Neonatal Sevoflurane Exposure-Induced Developmental Delays of Parvalbumin Interneurons and Cognitive Impairments Are Reversed by Environmental Enrichment.

Parvalbumin (PV) interneurons are critically involved in the cognitive processes. Based on prior investigations that environmental enrichment reverses impaired cognition after anesthetic exposure, we proposed that environmental enrichment protects PV interneurons and thereby improves sevoflurane-induced cognitive impairments. Six-day-old C57BL/6 male mice were exposed to 3 % sevoflurane or 30 % oxygen/air 2 h daily for 3 days from postnatal day 6 (P6) to P8. The mice were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or a standard environment. Western blotting and immunofluorescence were used for determining PV expression in the prefrontal cortex and hippocampus. In another set of experiments, cognitive tests were assessed by the open field test (P41), Morris water maze test (P54-60), and fear conditioning tests (P42-43 and P89-90). Exposure of neonatal mice to sevoflurane resulted in a reduced freezing response in the contextual test at P43 but not P90. The PV expression in these mice was decreased at P9, P14, P28, and P42, but not at ≥P60. No colocalization of caspase-3 and 5-bromo-2-deoxyuridine or caspase-3 and PV was observed, suggesting that caspase-independent pathways may be involved in the mediation of sevoflurane-induced down-regulation of PV. The sevoflurane-exposed mice that were placed in an enriched environment exhibited normal behavior and had PV interneurons that did not differ from those in the control mice at P42-43. Neonatal sevoflurane exposure induces a reduced freezing response in the contextual test at P43 and developmental delays in PV interneurons in the prefrontal cortex and hippocampus. Placement of the sevoflurane-exposed mice in an enriched environment can prevent these abnormalities.

Hypermethylation of Hippocampal Synaptic Plasticity-Related genes is Involved in Neonatal Sevoflurane Exposure-Induced Cognitive Impairments in Rats.

General anesthetics given to immature rodents cause delayed neurobehavioral abnormalities via incompletely understood mechanisms. DNA methylation, one of the epigenetic modifications, is essential for the modulation of hippocampal synaptic plasticity through regulating the related genes. Therefore, we investigated whether abnormalities in the hippocampal DNA methylation of synaptic plasticity-related genes are involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Male Sprague-Dawley rats were exposed to 3 % sevoflurane or 30 % oxygen/air for 2 h daily from postnatal day 7 (P7) to P9 and were treated with DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-AZA) or vehicle 1 h before the first sevoflurane exposure on P7. The rats were euthanized 1, 6, 24 h, and 30 days after the last sevoflurane exposure, and the brain tissues were harvested for biochemical analysis. Cognitive functions were evaluated by the open field, fear conditioning, and Morris water maze (MWM) tests on P39, P41-43, and P50-57, respectively. In the present study, repeated neonatal sevoflurane exposure resulted in hippocampus-dependent cognitive impairments as assessed by fear conditioning and MWM tests. The cognitive impairments were associated with the increased DNMTs and hypermethylation of brain-derived neurotrophic factor (BDNF) and Reelin genes, and subsequent down-regulation of BDNF and Reelin genes, which finally led to the decrease of dendritic spines in the hippocampal pyramidal neurons in adolescent rats. Notably, pretreatment with 5-AZA reversed these sevoflurane-induced abnormalities. In conclusion, our results suggest that hypermethylation of hippocampal BDNF and Reelin is involved in neonatal sevoflurane exposure-induced cognitive impairments.

Dexmedetomidine alleviates anxiety-like behaviors and cognitive impairments in a rat model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that has substantial health implications, including high rates of health morbidity and mortality, as well as increased health-related costs. Although many pharmacological agents have proven the effects on the development of PTSD, current pharmacotherapies typically only produce partial improvement of PTSD symptoms. Dexmedetomidine is a selective, short-acting α2-adrenoceptor agonist, which has anxiolytic, sedative, and analgesic effects. We therefore hypothesized that dexmedetomidine possesses the ability to prevent the development of PTSD and alleviate its symptoms. By using the rat model of PTSD induced by five electric foot shocks followed by three weekly exposures to situational reminders, we showed that the stressed rats displayed pronounced anxiety-like behaviors and cognitive impairments compared to the controls. Notably, repeated administration of 20µg/kg dexmedetomidine showed impaired fear conditioning memory, decreased anxiety-like behaviors, and improved spatial cognitive impairments compared to the vehicle-treated stressed rats. These data suggest that dexmedetomidine may exert preventive and protective effects against anxiety-like behaviors and cognitive impairments in the rats with PTSD after repeated administration.