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Aims We previously demonstrated that intrathecal IL-1β upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase ( iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide ( NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1β-induced nociception in rats. Methods The pretreatment effects of MK-801 (5 μg), minocycline (20 μg), and SB203580 (5 μg) on intrathecal IL-1β (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies. Results IL-1β increased phosphorylation of NR-1 (p- NR1) subunit of N-methyl-D-aspartate receptors in neurons and microglia, reduced glutamate transporters ( GTs; glutamate/aspartate transporter by 60.9%, glutamate transporter-1 by 55.0%, excitatory amino acid carrier-1 by 39.8%; P<.05 for all), and increased glutamate (29%-133% increase from 1.5 to 12 hours; P<.05) and NO (44%-101% increase from 4 to 12 hours; P<.05) levels in cerebrospinal fluid. MK-801 significantly inhibited all the IL-1β-induced responses; however, minocycline and SB203580 blocked the IL-1β-downregulated GTs and elevated glutamate but not the upregulated p- NR1. Conclusion The enhanced glutamatergic response and neuron-glia interaction potentiate the intrathecal IL-1β-activated P-p38/ iNOS/ NO signaling and thermal hyperalgesia. [ABSTRACT FROM AUTHOR]

ABSTRACT We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system [ABSTRACT FROM AUTHOR]

Background: We investigated the analgesic efficacy of bilateral superficial cervical plexus block in patients undergoing thyroidectomy and to determine whether it reduces the adverse effects of general anesthesia. Methods: We prospectively recruited 162 patients who underwent elective thyroid operations from March 2006 to October 2007. They were randomly assigned to receive a bilateral superficial cervical block (12 ml per side) with isotonic saline (group A; n = 56), bupivacaine 0.5% (group B; n = 52), or levobupivacaine 0.5% (group C; n = 54) after induction of general anesthesia. The analgesic efficacy of the block was assessed with: intraoperative anesthetics (desflurane), numbers of patients needing postoperative analgesics, the time to the first analgesics required, and pain intensity by visual analog scale (VAS). Postoperative nausea and vomiting (PONV) for 24 h were also assessed by the “PONV grade.” We also compared hospital stay, operative time, and discomfort in swallowing. Results: There were no significant differences in patient characteristics. Each average end-tidal desflurane concentration was 5.8, 3.9, and 3.8% in groups A, B, and C, respectively ( p < 0.001). Fewer patients in groups B and C required analgesics (A: B: C = 33:8:7; p < 0.001), and it took longer before the first analgesic dose was needed postoperatively (group A: B: C = 82.1:360.8:410.1 min; p < 0.001). Postoperative pain VAS were lower in groups B and C for the first 24 h postoperatively ( p < 0.001). Incidences of overall and severe PONV were lower, however, there were not sufficient numbers of patients to detect differences in PONV among the three groups. Hospital stay was shorter in group B and group C ( p = 0.011). There was no significant difference in operative time and postoperative swallowing pain among the three groups. Conclusions: Bilateral superficial cervical plexus block reduces general anesthetics required during thyroidectomy. It also significantly lowers the severity of postoperative pain during the first 24 h and shortens the hospital stay. [ABSTRACT FROM AUTHOR]

Previously we showed that coadministration of dextromethorphan (DM) with morphine attenuates morphine-rewarding effect. Here we further investigated if DM is effective in reversing or treating drug-seeking effect when given after subchronic morphine treatment. The conditioned place preference (CPP) test was used to investigate the rewarding and drug-seeking effects of morphine. Rats were injected and conditioned with morphine for 6 days and then withdrawn from morphine for 4 days and treated with saline or DM during this period. Subchronic morphine induced a significant place preference for the drug-paired compartment. DM treatment during the morphine withdrawal period significantly reversed the preference from the drug-paired compartment to saline-paired compartment. Both nucleus accumbens (NAc) and VTA were proven to be the sites involved in the action of DM. Behavioral sensitization occurred in both morphine group and DM treatment group determined by the locomotor activity before and after subchronic morphine treatment. The dopamine (DA) turnover rate in the NAc, dorsal striatum (DS) and medial prefrontal cortex (mPFC) was increased after subchronic morphine treatment. DM treatment reversed the increase of DA turnover rate in the NAc but not in the DS or mPFC. These data suggest that DM might have potential in the treatment of morphine addiction. Synapse 61:420-428, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase ( nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREBSerine-133), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28-29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREBSerine-133, and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We previously reported increased release of the excitatory amino acid (EAA) neurotransmitters, glutamate and aspartate, during the early stage of experimental osteoarthritis (OA). Our present objective was to study the effect of intraarticular injection of hyaluronic acid (HA) on OA development, and to analyze concomitant changes in EAA levels in dialysates of anterior cruciate ligament-transected (ACLT) knee joints. OA was induced in Wistar rats by ACLT of one hindlimb; the knee of the other hindlimb was used as the sham-operated control. HA group ( n = 12) were injected intraarticularly in the ACLT knee with 1 mg of HA once a week for 5 consecutive weeks, starting at 8 weeks after surgery. Saline group ( n = 12) were injected as above with normal saline. The sham-operated group, underwent arthrotomy, but not ACLT, and received no treatment ( n = 14). Twenty weeks after surgery, knee joint dialysates were collected by microdialysis and EAA levels assayed by high-performance liquid chromatography, and gross morphological examination and histopathological evaluation were performed on the medial femoral condyles and synovia. Rats receiving intraarticular HA injections showed a significantly lower degree of cartilage degeneration on the medial femoral condyle at both the macroscopic level and on the Mankin grading scale than rats receiving saline injections. Intraarticular HA treatment also suppressed synovitis. Moreover, glutamate and aspartate levels were significantly reduced in the HA group compared to the saline group. Intraarticular injection of HA limits articular cartilage and synovium damage and OA formation, and, in parallel, reduces EAA levels in ACLT joint dialysates. This study suggests that the underlying mechanism of the anti-inflammatory effect of HA is to inhibit glutamate and aspartate release in ACLT knee joints, which attenuates the early development of OA. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [ABSTRACT FROM AUTHOR]

Abstract: Changes in excitatory amino acid (EAA) levels were examined in the knee joint dialysates of rats with early osteoarthritis (OA). Early OA was induced by anterior cruciate ligament (ACL) transection in one knee and the contralateral knee was used as the sham-operated control, the side for ACL transection being assigned randomly. Twenty weeks after operation, knee joint dialysates were collected by microdialysis and assayed for EAAs by high performance liquid chromatography. The rats were then sacrificed for histopathological examination. Hematoxylin/eosin and Safranin-O staining showed cartilage fibrillation, clustering of chondrocytes, and a reduction in matrix proteoglycans at week 20 in the ACL-transected knee, but not in the sham-operated knee. Levels of glutamate and aspartate in dialysates from the ACL-transected knee were significantly increased by 92±20.3% or 57±17.5%, respectively, compared to those in the contralateral sham-operated knee. This increase may contribute to the pathogenesis of early OA. [Copyright &y& Elsevier]

Previous studies showed that ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, provides a preemptive analgesic effect and preemptive analgesia improves postoperative pain management. The aim of this study was to examine whether premedication with dextromethorphan (DM) improves postoperative pain management after upper abdominal surgery. Sixty (American Society of Anesthesiologists class 1 and 2 of either gender) patients scheduled for upper abdominal surgery were included in the study. Patients were randomly assigned to one of four groups: control, DM-10, DM-20, and DM-40. In the control group, chlorpheniramine maleate (CPM, 20 mg) was injected immediately before induction of anesthesia intramuscularly (IM). In the DM-10, DM-20, and DM-40 groups, patients were premedicated with DM 10 mg, 20 mg, and 40 mg IM, respectively. After operation, patient-controlled analgesia (PCA) with morphine was given for pain relief. The time to the first PCA trigger, morphine consumption, pain scores, and analgesic-related side effects were recorded at 1, 2, 4, 24, 48, and 72 hours after surgery. The time to first PCA trigger for the control group was 17.8 ± 1.4 minutes, for group DM-10 20.2 ± 1.6 minutes, for group DM-20 32.4 ± 1.9 minutes, and for DM-40 77.9 ± 6.5 minutes. The morphine delivered and PCA triggering frequency were 5.5 ± 0.5/11.3 ± 0.8 times for the controls, 5.5 ± 0.4/14.1 ± 1.3 times for DM-10, 3.1 ± 0.3/6.3 ± 1.2 times for DM-20, and 0.2 ± 0.1/0.3 ± 0.2 times for DM-40 during the first hour after operation. For the first day, the figures are 19.9 ± 1.2/23.9 ± 1.4 for the controls, 15.6 ± 1.2/17.3 ± 2.4 for DM-10, 12.6 ± 0.7/15.9 ± 1.6 for DM-20, and 5.0 ± 0.21/5.6 ± 0.9 for DM-40. On the first day, the cough pain scores were 6.67 ± 0.23, 6.53 ± 0.16, 6.67 ± 0.23, and 5.73 ± 0.18 for the controls, DM-10, DM-20, and DM-40 groups, respectively. All data showed dose-dependent better pain relief in DM-premedicated patients. We conclude that DM premedication offers preemptive analgesia and reduces postoperative pain and morphine requirement. [ABSTRACT FROM AUTHOR]

< 0.001) and decreased pethidine consumption (17.2 ± 7.0 vs. 76.3 ± 17.4 mg) ( p < 0.001) were observed in the TEA group than in the GA group, respectively. A worse visual analog scale (VAS) pain score was observed in the GA group (5.7 ± 0.6) than in TEA patients (4.3 ± 0.4) ( p < 0.01). The average bed rest time was significantly shorter in the TEA group (16.9 ± 0.9 hours) ( p < 0.01) than in the GA group (27.1 ± 4.1 hours). Overall satisfaction scores were significantly higher in the TEA group (4.4 ± 0.1) ( p < 0.01) than in the GA group (3.5 ± 0.2). Side effects were observed at a higher frequency in the GA group (16/32) ( p < 0.0001) than in the TEA group (3/32). The frequency of pethidine injection for pain relief was significantly lower in the TEA group (8/32) ( p < 0.0001) than in the GA group (24/32). The total hospital cost (NT 64,392 ± 3,523 vs. NT 53,806 ± 2,817) ( p= 0.0342) and anesthesia cost (NT 7,968 ± 246 vs. NT 5,268 ± 262) ( p < 0.0001) are also significantly lower in the TEA group than the GA group. In conclusion, TEA provided better postoperative pain relief and recovery and lower cost than GA for MRM surgery. [ABSTRACT FROM AUTHOR]

Purpose: Although difficult laryngeal exposure (DLE) is a common problem encountered after procedures using a rigid laryngoscope, to date, no anticipatory physical indicators have been formally noted as reliable predictors of DLE. The purpose of this paper is to identify useful and reliable indicators by which to predict, with acceptable accuracy, the occurrence of DLE following rigid laryngoscopy., Study Design: Fifty-six patients, each of whom had undergone a rigid laryngoscope procedure, were classified as belonging to either the DLE group (n = 19) or the control group (n = 37) for purposes of this prospective study., Methods: All patients were given a physical examination, which encompassed the following nine measures: age, sex, modified Mallampati index (MMI), body mass index (BMI), hyoid-mental distance (HMD), thyroid-mental distance (TMD), thyroid-mandible angle (TMA), horizontal thyroid distance (HTD), and vertical thyroid distance (VTD). Stepwise regression was employed on patient data to identify those with DLE. RESULTS The ages of patients in the DLE group ranged from 35 to 79 years, with a mean of 51.3 years. Among the nine variables, we found sex (P =.045, odds ratio = 69.159) and TMA (P =.004, odds ratio = 1.510) to be "reliable" DLE predictors. Using these two variables, 94.6% of study case patients could have been correctly classified preoperatively. Based on our comparison of case results, we found that a TMA value greater than 120 degrees in men and 130 degrees in women indicates a strong likelihood of DLE. CONCLUSIONS TMA is a sensitive, reliable, and useful predictor of DLE in both men and women. The combination of sex and TMA provide important initial clinical indicators that can alert a clinician regarding DLE probability.