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Expression of the mu-opioid receptor (MOR) is associated with poor long-term outcomes in various types of cancer. The association between MOR expression and clinical outcomes in laryngeal squamous cell carcinoma (LSCC) is not clear.This retrospective study included patients who underwent laryngectomy for LSCC. The expression pattern of the MOR protein and OPRM1 gene in tumours and corresponding adjacent non-carcinoma specimens was measured. Propensity score matching was used to minimise bias. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were intraoperative sufentanil consumption, grade of surgical complications according to the Clavien-Dindo classification, and hospital length of stay.A total of 207 LSCC patients were enrolled. After propensity score matching, there was a significant difference in DFS between groups at 1, 3, and 5 yr (60.2% vs 81.2%, P=0.019; 39.4% vs 50.2%, P=0.026; 37.5% vs 42.5%, P=0.023, respectively) in patients with high MOR expression. The OS rates at 1, 3, and 5 yr were significantly lower in the high MOR expression group (81.2% vs 93.2%, P=0.027; 57.7% vs 78.3%, P0.001; 42.5% vs 60.3%, P0.001, respectively). The multivariate analysis indicated that high MOR expression was associated with worse DFS and OS (hazard ratio: 1.52, 95% confidence interval: 1.07, 2.25, P=0.034; hazard ratio: 1.42, 95% confidence interval: 1.17, 2.34, P=0.032).High MOR expression may be associated with poor prognosis in patients with LSCC, suggesting that MOR could be used as a valuable molecular biomarker to predict prognosis of LSCC patients.

To explore the efficacy and safety of etoposide + cisplatin (EP) and irinotecan + cisplatin (IP) sequential chemotherapy combined with radiotherapy in the treatment of extensive-stage small-cell lung cancer (SCLC).A total of 108 patients with extensive-stage SCLC were divided into the EP+IP group (n=54, sequential IP chemotherapy), and the EP group (n=54, EP chemotherapy). The changes in the level of serum tumor markers and the number of circulating tumor cells (CTCs) in the peripheral blood were compared between the two groups of patients before and after treatment. The patients were followed up to record the survival status and tumor progression.The overall effective rate for bone metastases in the EP+IP group was significantly higher than that in the EP group. The EP+IP group displayed significantly lower levels of serum VEGF, Ki-67 and peripheral blood CTCs than the EP group. In addition, the follow-up results manifested that the median overall survival (OS) in the EP+IP group and the EP group were 16.2 months and 12.7 months, respectively, and the median progression-free survival (PFS) was 8.4 months and 5.9 months, respectively. The 2-year OS was 13.0% and 7.4%, respectively. Furthermore, the log-rank test illustrated that the OS and PFS in the EP+IP group were significantly superior to those in the EP group.EP and IP sequential chemotherapy combined with radiotherapy is more effective than EP chemotherapy combined with radiotherapy in the treatment of extensive-stage SCLC. The former can markedly reduce the levels of serum tumor markers and peripheral blood CTCs, increase the long-term survival of patients and reduce the occurrence of blood-related adverse reactions.

Background Delayed neurocognitive recovery after surgery is associated with poor outcome. Most surgeries require general anesthesia, of which sevoflurane and propofol are the most commonly used inhalational and intravenous anesthetics. The authors tested the primary hypothesis that patients with laparoscopic abdominal surgery under propofol-based anesthesia have a lower incidence of delayed neurocognitive recovery than patients under sevoflurane-based anesthesia. A second hypothesis is that there were blood biomarkers for predicting delayed neurocognitive recovery to occur. Methods A randomized, double-blind, parallel, controlled study was performed at four hospitals in China. Elderly patients (60 yr and older) undergoing laparoscopic abdominal surgery that was likely longer than 2 h were randomized to a propofol- or sevoflurane-based regimen to maintain general anesthesia. A minimum of 221 patients was planned for each group to detect a one-third decrease in delayed neurocognitive recovery incidence in propofol group compared with sevoflurane group. The primary outcome was delayed neurocognitive recovery incidence 5 to 7 days after surgery. Results A total of 544 patients were enrolled, with 272 patients in each group. Of these patients, 226 in the propofol group and 221 in the sevoflurane group completed the needed neuropsychological tests for diagnosing delayed neurocognitive recovery, and 46 (20.8%) in the sevoflurane group and 38 (16.8%) in the propofol group met the criteria for delayed neurocognitive recovery (odds ratio, 0.77; 95% CI, 0.48 to 1.24; P = 0.279). A high blood interleukin-6 concentration at 1 h after skin incision was associated with an increased likelihood of delayed neurocognitive recovery (odds ratio, 1.04; 95% CI, 1.01 to 1.07; P = 0.007). Adverse event incidences were similar in both groups. Conclusions Anesthetic choice between propofol and sevoflurane did not appear to affect the incidence of delayed neurocognitive recovery 5 to 7 days after laparoscopic abdominal surgery. A high blood interleukin-6 concentration after surgical incision may be an independent risk factor for delayed neurocognitive recovery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Dopamine and dopamine receptor D1 (DRD1), a member of the dopamine receptor family, have been indicated to play important roles in cancer progression, but dopamine secretion in hepatocellular carcinoma (HCC) and the effects of DRD1 on HCC remain unclear. This study was designed to explore the contribution of the dopaminergic system to HCC and determine the relationship between DRD1 and prognosis in HCC patients. Methods The dopamine metabolic system was monitored using enzyme‐linked immunosorbent assays (ELISAs). The expression of DRD1 was detected by microarray analysis, immunohistochemistry (IHC), and quantitative real‐time PCR (qRT‐PCR). Stable DRD1 knockout and overexpression cell lines were established for investigation. Transwell, colony formation, and Cell Counting Kit 8 (CCK8) assays were performed to assess the malignant behaviors of cancer cells. The cAMP/PI3K/AKT/ cAMP response element‐binding (CREB) signaling pathway was evaluated by Western blot. This pathway, which is agitated by DRD1 in striatal neurons, had been proven to participate in tumor progression. Xenograft HCC tumors were generated for in vivo experiments. Results Dopamine secretion increased locally in HCC due to an imbalance in dopamine metabolism, including the upregulation of dopa decarboxylase (DDC) and the downregulation of monoamine oxidase A (MAOA). Dopamine promoted the proliferation and metastasis of HCC. DRD1 was highly expressed in HCC tissues and positive DRD1 expression was related to a poor prognosis in HCC patients. The upregulation of DRD1 agitated malignant activities, including proliferation and metastasis in HCC by regulating the cAMP/PI3K/AKT/CREB pathway, and the downregulation of DRD1 had opposing effects. The effects of dopamine on HCC was reversed by depleting DRD1. SCH23390, a selective DRD1 antagonist, inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo. Conclusion Dopamine secretion was locally increased in HCC and promoted HCC cell proliferation and metastasis. DRD1 was found to exert positive effects on HCC progression and play a vital role in the dopamine system, and could be a potential therapeutic target and prognostic biomarker for HCC.

Antitubulin chemotherapeutics agents, such as paclitaxel, are effective chemotherapy drugs for cancer treatment. However, painful neuropathy is a major adverse effect limiting the wider application of chemotherapeutics. In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or AKAP150flox/flox in rodents alleviated the pain behavior induced by paclitaxel, and partly restored the decreased calcineurin (CN) phosphatase activity after paclitaxel treatment. Paclitaxel decreased the expression of anti-inflammatory cytokine interleukin-4 (IL-4), and intrathecal injections of IL-4 effectively alleviated paclitaxel-induced hypersensitivity and the frequency of dorsal root ganglion (DRG) neurons action potential. The decreased CN enzyme activity, resulted in reduced protein expression of nuclear factor of activated T cells 2 (NFAT2) in cell nuclei. Chromatin immunoprecipitation showed that, NFAT2 binds to the IL-4 gene promoter regulating the protein expression of IL-4. Overexpression of NFAT2 by intrathecal injection of the AAV5-NFAT2-GFP virus alleviated the pain behavior induced by paclitaxel via increasing the expression of IL-4. Knocked down AKAP150 by siRNA or AAV5-Cre-GFP partly restored the expression of IL-4 in DRG. Our results indicated that regulation of IL-4 via the CN/NFAT2 pathway mediated by AKAP150 could be a pivotal treatment target for paclitaxel-induced neuropathic pain and or other neuropsychiatric disorders.

Chemotherapy-induced peripheral neuropathy is a serious adverse effect of chemotherapeutic agents such as paclitaxel. JTC-801, a nociceptin/orphanin FQ opioid peptide (NOP) receptor antagonist, has been reported to attenuate neuropathic pain in several pain models. However, the therapeutic significance and function of JTC-801 in chemotherapy-induced peripheral neuropathy remain unclear. In this study, we determined the effect of JTC-801 on neuropathic pain induced by paclitaxel, and we explored the potential mechanism in the dorsal root ganglion (DRG). The behavioral test showed that single or multiple systemic administrations of JTC-801 significantly alleviated mechanical allodynia in paclitaxel-treated rats. Using Western blot analysis and immunohistochemistry, we found that paclitaxel increased the expression of phosphatidylinositol 3-kinase (PI3K) and phospho-Akt (p-Akt) in the DRG. Double immunofluorescence staining indicated that p-Akt was expressed in neurons in the DRG. Multiple injections of JTC-801 significantly inhibited the activation of Akt and decreased the expression of inflammatory cytokines. The data suggest that JTC-801 alleviates mechanical allodynia associated with paclitaxel-induced neuropathic pain via the PI3K/Akt pathway.

Background Opioid receptors are implicated in cancer progression and long-term patient outcomes. However, the prognostic significance, underlying mechanisms, and therapeutic value of mu-opioid receptor (MOP) in hepatocellular carcinoma (HCC) remain unclear. Methods MOP expression in human biopsy HCC samples was evaluated using RNA microarrays, quantitative real-time polymerase chain reaction (qRT-PCR), and immunochemical analyses. Molecular and cellular techniques, including siRNA-mediated depletion and lentiviral vector-mediated overexpression, were used to elucidate the functions and mechanisms of MOP. The effect of the MOP agonist morphine in HCC was evaluated both in vitro and in vivo. The therapeutic value of MOP inhibitors in HCC progression and metastasis was investigated with in vitro experiments and subcutaneous and orthotopic HCC mouse models in vivo. Results Through microarray analysis and qRT-PCR, we identified that MOP is highly expressed in human HCC tumours. High MOP expression in HCC tumours was confirmed by immunocytochemistry and correlated with aggressive clinicopathological features and a worse prognosis. Depletion of MOP suppressed cell proliferation, migration, and invasion, whereas overexpression of MOP promoted cell growth and metastasis in human HCC cell lines. Both clinical and biological evidence revealed that MOP-mediated epithelial-mesenchymal transition promotes HCC metastasis and poor prognosis. Morphine promotes cell proliferation, migration, and invasion in vitro and in vivo in mouse models. More importantly, MOP inhibitors suppressed cell growth, invasion, and metastasis in vitro and in the subcutaneous and orthotopic xenograft models. Conclusions MOP plays a key oncogenic function in hepatocarcinogenesis. Its overexpression is associated with poor prognosis in patients with HCC. Furthermore, MOP inhibitors may be a promising strategy for HCC therapy.

Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often induce peripheral neuropathic pain. It is usually permanent and seriously harmful to cancer patients' quality of life and can result in the hampering of clinical treatments. Currently, there is no definitive therapy, and many of the drugs approved for the treatment of other neuropathic pain have shown little or no analgesic effect. It is therefore vital to find new and novel therapeutic strategies for patients suffering from chemotherapeutic agent-induced neuropathic pain to improve patients' quality of life. This study shows that intrathecal injections of dexmedetomidine (DEX), or intraperitoneally administered ulinastatin (UTI) significantly reduces Sprague Dawley rats' mechanical allodynia induced by VCR via upregulation of interleukin-10 expression and activating the α2-adrenergic receptor in dorsal root ganglion (DRG). Moreover, when combined there is a synergistic interaction between DEX and UTI, which acts against VCR-induced neuropathic pain. This synergistic interaction between DEX and UTI may be partly attributed to a common analgesic pathway in which the upregulation of interleukin -10 plays an important role via activating α2-adrenergic receptor in rat dorsal root ganglion. The combined use of DEX and UTI does not affect the rat's blood pressure, heart rate, sedation, motor score, spatial learning, or memory function. All of these show that the combined use of DEX and UTI is an effective method in relieving VCR-induced neuropathic pain in rats. Perspective This article documents the synergistic interaction between 2 widely used drugs, DEX and UTI, against VCR-induced neuropathic pain. The results provide a potential target and novel drug administrated method for the clinical treatment of chemotherapy-induced peripheral neuropathic pain.

Associations between anesthetic management and cancer recurrence or long-time survival remain uncertain. In this study, we compared the effects of postoperative epidural morphine analgesia with that of postoperative IV fentanyl analgesia on cancer recurrence and long-term survival in patients undergoing resection of hepatocellular carcinoma.A retrospective cohort study was performed on patients with hepatocellular carcinoma receiving hepatic resection at this institution (n = 1846, 1997-2007). Recurrence-free survival and long-term survival were assessed using Kaplan-Meier survival estimates and compared using a multivariate Cox proportional hazards regression, adjusted with propensity scores.Eight hundred nineteen patients met the inclusion criteria and were divided into 2 groups: patients receiving postoperative epidural analgesia with morphine (EA, n = 451) and patients receiving postoperative IV analgesia with fentanyl (IA, n = 368). The median time of follow-up for all patients was 4.2 years (2-9). The rates of recurrence of cancer (37.7% vs 30.7%, P = 0.036) and death (40.6% vs 30.4%, P = 0.003) were higher in the EA group versus IA group. Recurrence-free survival was similar in both the EA and IA groups (hazards ratio 2.224, 95% confidence interval, 0.207-23.893, P = 0.509). Using a multivariate Cox proportional hazards regression adjusted with propensity scores, independent risk factors for long-term survival in patients after resection of hepatocellular carcinoma were ASA physical status, tumor diameter, preoperative α-fetoprotein (+) as well as postoperative epidural analgesia with morphine.Compared with postoperative IV analgesia with fentanyl, postoperative epidural analgesia with morphine was associated with increased cancer recurrence and death but had no significant effect on recurrence-free survival in patients undergoing resection of hepatocellular carcinoma.

The aims of this study were to evaluate the anti-inflammatory and analgesic effects of bufalin, a major component of “Chan-su.” We used a carrageenan-induced paw edema model to assess the anti-inflammatory activity of this compound, and Western blot analysis detected NF-κB signaling during this effect. The antinociceptive activities were evaluated by acetic acid-induced writhing, formalin, and hot-plate tests; open-field test investigated effects on the central nervous system. Our data showed that bufalin (0.3 and 0.6 mg/kg, i.p.) potently decreased carrageenan-induced paw edema. Bufalin down regulated the expression levels of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β(IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α) during these treatments. Further studies demonstrated that bufalin significantly inhibited the activation of NF-κB signaling. Bufalin also reduced acetic acid-induced writhing and the licking time in the formalin test and increased hot-plate reaction latencies. Naloxone pretreatment (2 mg/kg, i.p.) in the early phases of the formalin test and hot-plate test significantly attenuated the bufalin-induced antinociception effects, which suggests the involvement of the opioid system. A reduction in locomotion was not observed in the open-field test after bufalin administration. Taken together, bufalin treatment resulted in in vivo anti-inflammatory and analgesic effects, and bufalin may be a novel, potential drug for the treatment of inflammatory diseases.

Background Opioid receptors have become increasingly implicated in cancer progression and long-term patient outcomes. However, the expression and significance of the κ-opioid receptor (KOR) in hepatocellular carcinoma (HCC) remain unclear. Methods In this study, KOR mRNA expression was analysed by real-time quantitative PCR in 64 pairs of HCC tumour tissues and adjacent non-tumour tissues, and KOR protein expression was analysed by immunohistochemistry in 174 HCC patients. We investigated the correlation between KOR expression and clinicopathological parameters to illustrate the potential prognostic significance of KOR expression in HCC. Results KOR mRNA expression was significantly down-regulated in 79.69% (51 of 64) of the HCC tumour samples, and KOR expression in tumour tissue was significantly lower than that in adjacent non-tumour tissues (P

Several ionic channels, receptors and enzymes have been reported to be affected by amiloride. It is known to act on pharmacological target sites that are implicated in pain processing. Tizanidine is a centrally acting alpha2-adrenoceptor agonist used in the treatment of muscle spasms. The effectiveness of the antinociceptive interaction of amiloride and tizanidine was investigated using the rat formalin test., BACKGROUND: Amiloride has been reported to produce a wide variety of actions, thereby affecting several ionic channels and a multitude of receptors and enzymes. Intrathecal α2-adrenergic receptor agonists produce pronounced analgesia, and amiloride modulates α2-adrenergic receptor agonist binding and function, acting via the allosteric site on the α2A-adrenergic receptor. OBJECTIVES: To investigate the antinociceptive interaction of intrathecal amiloride and the α2-adrenoceptor agonist tizanidine using a rat formalin test. METHODS: Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters and were tested for paw flinching using formalin injection. Biphasic painful behaviour was recorded. Amiloride, tizanidine or an amiloride-tizanidine mixture was administered 10 min before formalin injection. To characterize any interactions, isobolographic analysis was performed. The effects of a pretreatment using intrathecally administered yohimbine was also tested. RESULTS: Intrathecally administered amiloride (12.5 μg to 100 μg) and tizanidine (0.5 μg to 5 μg), given separately, produced a significant dose-related suppression of the biphasic responses in the formalin test. Isobolographic analysis revealed that the combination of intrathecal amiloride and tizanidine synergistically reduced phase I and II activities. Intrathecally administered yohimbine antagonized or attenuated the antinociceptive effect of amiloride, tizanidine and the amiloride-tizanidine mixture. Intrathecally administered amiloride synergistically interacts with tizanidine to reduce the nociceptive response in the formalin test, most likely by activating α2-adrenoceptors in the spinal cord. CONCLUSIONS: Although intrathecal tizanidine produced pronounced analgesia, antinociceptive doses of intrathecal tizanidine also produced several side effects, including bradycardia and sedation. Amiloride produced antinociceptive action against the thermal nociceptive test without side effects in rats.

BACKGROUND: Previous studies have shown that anaesthetic technique can affect outcomes of cancer surgery. We investigated the association between anaesthetic technique and patient outcomes after elective hepatectomy for hepatocellular carcinoma. METHODS: This was a retrospective single-centre cohort study of patients who received elective hepatectomy for hepatocellular carcinoma from January 2005 to December 2014. Patients were grouped according to propofol or desflurane anaesthesia. Kaplan–Meier analysis was performed and survival curves were constructed from the date of surgery to death. After propensity matching, univariable and multivariable Cox regression models were used to compare hazard ratios for death. Subgroup analyses were performed for tumour–node–metastasis staging and distant metastasis and local recurrence. RESULTS: A total of 492 patients (369 deaths, 75.0%) with desflurane anaesthesia and 452 (139 deaths, 30.8%) with propofol anaesthesia were eligible for analysis. After propensity matching, 335 patients remained in each group. In the matched analysis, propofol anaesthesia had a better survival with hazard ratio of 0.47 (95% confidence interval, 0.38–0.59; P

The antinociceptive effect produced by spinal injection of clonidine (an alpha(2)-adrenergic agonist) is mediated by a cholinergic mechanism. We aimed in the current study to evaluate the antinociceptive interaction between intrathecally administered ouabain, an inhibitor of Na(+), K(+)-ATPase, and clonidine. We used rats chronically implanted with lumbar intrathecal catheters to examine the ability of intrathecal clonidine and ouabain and the mixtures of clonidine-ouabain to alter tail-flick latency. To characterize the interaction, isobolographic analysis was performed. Intrathecal clonidine (0.5-10 microg) and ouabain (0.1-5 microg) produced significant dose- and time-dependent antinociception in the tail-flick tests. The median effective dose (ED(50)) values for intrathecally administered ouabain and clonidine were 2.3 microg and 4.7 microg, respectively. The experimental point for the ouabain-clonidine combination decreased significantly (P.05) below the lines of additivity. Isobolographic analysis exhibited a synergistic interaction after the coadministration of ouabain and clonidine. No motor impairment was observed in the animals after intrathecal administration of the combination of ouabain and clonidine or clonidine alone. Intrathecal pretreatment with atropine but not yohimbine blocked the antinociceptive effect of ouabain and attenuated its interaction with spinal clonidine. These results suggest that the synergistic interaction of ouabain and clonidine were probably mediated, at least in part, via an enhancement of cholinergic transmission in the spinal nociceptive processing system.Although intrathecal clonidine produces pronounced analgesia, antinociceptive doses of intrathecal clonidine produce several side effects, including hypotension, bradycardia, and sedation. This article presents antinociceptive synergistic interaction between clonidine and ouabain on thermal nociceptive tests in the rat.

Background Intestinal ischemia–reperfusion injury (IRI) is a clinical challenge with high morbidity and mortality, leading to intestine damage, systemic inflammation, and multiorgan failure. Previous research has shown that the inhaled anesthetic sevoflurane protects various organs from IRI. However, whether sevoflurane protects against intestinal IRI and which application condition is the most effective are not completely clear. Thus, we investigated the effects of sevoflurane on intestinal IRI with sevoflurane given before, during or after intestinal ischemia, and the role of phosphatidylinositol 3 kinases (PI3K)/Akt pathway in these effects. Methods Rat model of intestinal ischemia–reperfusion (IR) was used in this study. The superior mesenteric artery was clamped for 60 minutes followed by 120 minutes of reperfusion. Sevoflurane at 0.25, 0.5, and 1.0 minimum alveolar concentration (MAC) was inhaled for 30 minutes before, during, or after ischemic insult. LY294002, a PI3K inhibitor, was injected intraperitoneally before sevoflurane inhalation. Results Intestinal IR caused a significant decrease of mean arterial blood pressure, severe intestinal mucosa injury and epithelial cell apoptosis, downregulation of the levels of phospho-Akt and phospho-Bad proteins. Exposure to 0.5 or 1.0 MAC sevoflurane before or after intestinal ischemia or 0.5 MAC during intestinal ischemia significantly ameliorated IR-induced histopathologic changes and decreased Chiu's scores. Pretreatment with 0.5 MAC sevoflurane also inhibited intestinal IR-induced increase of terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling–positive cells and activation of caspase-3 and restored expression of phospho-Akt and phospho-Bad. LY294002 partly blocked the protective effects induced by 0.5 MAC sevoflurane pretreatment. Conclusion Our results suggest that sevoflurane inhalation at clinical related concentration before, during, or after ischemia protects against IR-induced intestinal injury. The pretreatment-induced protection was partly mediated by inhibiting intestinal mucosal epithelial apoptosis via activation of the PI3K/Akt pathway.

Background The Na+,K+-adenosine triphosphatase is a ubiquitous enzyme system that maintains the ion gradient across the plasma membrane of a variety of cell types, including cells in the central nervous system. We investigated the antinociceptive effect of intrathecally administered ouabain and examined its potential interaction with spinal morphine and lidocaine. Methods Using rats chronically implanted with lumbar intrathecal catheters, the ability of intrathecally administered ouabain, morphine, and lidocaine and of mixtures of ouabain-morphine and ouabain-lidocaine to alter tail-flick latency was examined. To characterize any interactions, isobolographic analysis was performed. The effects of pretreatment with intrathecally administered atropine or naloxone also were tested. Results Intrathecally administered ouabain (0.1-5.0 microg), morphine (0.2-10.0 microg), and lidocaine (25-300 microg) given alone produced significant dose- and time-dependent antinociception, but systemic administration of ouabain did not produce such an effect. The median effective dose (ED50) values for intrathecally administered ouabain, morphine, and lidocaine were 2.3, 5.0, and 227.0 microg, respectively. Isobolographic analysis exhibited a synergistic interaction after the coadministration of ouabain and morphine. With ouabain and lidocaine, there was no such evidence of synergism. Intrathecally administered atropine, but not naloxone, completely blocked the antinociceptive effect of ouabain and attenuated its interaction with spinally administered morphine. Conclusions Intrathecally administered ouabain produces antinociception, at least in part, via an enhancement of cholinergic transmission in the spinal nociceptive processing system. The results of the interaction of ouabain with morphine and lidocaine suggest that modulation of Na+-,K+-electrochemical gradients and thus subsequent release of neurotransmitters in the spinal cord are likely to play important roles in the spinal antinociceptive effect of intrathecally administered ouabain.

The effect of thoracic epidural analgesia (TEA) on anastomotic leakage (AL) after anterior resection for colorectal cancer is controversial. The aim of this study was to evaluate the risk factors including TEA for the occurrence of AL after anterior resection for colorectal cancer. This retrospective study included 1,312 patients with colorectal cancer who underwent anterior resection between 2000 and 2011 at the Cancer Center, Sun Yat-sen University. Univariate and multivariate logistics analyses were performed to determine the risk factors, including TEA, for AL. Additionally, we evaluated the effect of TEA on outcome parameters. AL occurred in 118 (9 %) of the 1,312 patients. In univariate analysis, the American Society of Anesthesiologists (ASA) score, history of hypertension, episodes of hypotension, anastomosis technique, tumor localization, anesthesia duration, and perioperative blood transfusion were significant risk factors for AL. Multivariate analysis showed that ASA (P = 0.001), perioperative blood transfusion (P

The beta2-adrenergic receptor (Beta2-AR) is overexpressed and highly associated with poor prognosis in many malignancies. Nevertheless, the role of Beta2-AR in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. The aim of this study is to investigate the expression of Beta2-AR and its clinicopathological/prognostic value in HCC patients after curative resection. Semiquantitative reverse transcription PCR (RT-PCR) and real-time quantitative PCR (qPCR) were used to measure Beta2-AR RNA expression in 60 pairs of HCC tumors and matched nontumorous tissues. Beta2-AR expression was detected in HCC cell lines by Western blot analysis. Furthermore, we investigated Beta2-AR expression in correlation with the clinicopathological features and analyzed the potential prognostic significance of Beta2-AR in 192 HCC patients by immunohistochemistry (IHC). Upregulation of Beta2-AR mRNA was significantly higher in HCC tumor tissues than in their paired nontumorous liver specimens. The expression of Beta2-AR protein was detected in five HCC cell lines. Positive Beta2-AR protein expression was significantly associated with a high α-fetoprotein (AFP) level (P = 0.001), large tumor size (P

In this study, we aimed to evaluate the antinociceptive interaction between intrathecally administered amiloride and morphine or clonidine. Using rats chronically implanted with lumbar intrathecal catheters, we examined the ability of intrathecal amiloride, morphine, clonidine, and mixtures of amiloride-morphine and amiloride-clonidine to alter tail-flick latency. To characterize any interactions, isobolographic analysis was performed. The effects of pretreatment with intrathecally administered naloxone or yohimbine were tested. Intrathecal administration of amiloride (25–150 μg), morphine (.25–10 μg), or clonidine (.5–10 μg) alone produced significant dose-dependent antinociception in the tail-flick test. The median effective dose (ED 50 ) values for intrathecally administered amiloride, morphine, and clonidine were 120.5 μg, 5.0 μg, and 4.4 μg, respectively. Isobolographic analysis exhibited a synergistic interaction after coadministration of amiloride-morphine and amiloride-clonidine. Intrathecal pretreatment with naloxone (10 μg) completely blocked the antinociceptive effects of morphine and the amiloride-morphine mixture. Intrathecal pretreatment with yohimbine (20 μg) completely blocked the antinociceptive effect of clonidine and antagonized the effect of the amiloride-clonidine mixture. There was no motor dysfunction or significant change in blood pressure or heart rate after the intrathecal administration of amiloride, amiloride-morphine, and amiloride-clonidine. The synergistic effect observed after the coadministration of amiloride and morphine or clonidine suggests a functional interaction among calcium channels, μ-receptors and α 2 -receptors at the spinal cord level of the nociceptive processing system. Perspective Although intrathecal morphine and clonidine produces pronounced analgesia, antinociceptive doses of intrathecal morphine and clonidine produce several side effects, including hypotension, bradycardia, sedation, and tolerance. This article presents antinociceptive synergistic interaction between amiloride and morphine, amiloride, and clonidine on thermal nociceptive tests in the rat.