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- Effects of intrathecal opioids combined with low-dose naloxone on motilin and its receptor in a rat model of postoperative pain. [JOURNAL ARTICLE]
- Life Sci 2014 Apr 10.
To investigate the effects of intrathecal morphine and fentanyl combined with low-dose naloxone on expression of motilin and its receptor in a rat model of postoperative pain.An intrathecal catheter was implanted, and saline, opioids (morphine and fentanyl) and naloxone were inrathecally administered 7days later. An incisional pain model was established to induce pain behaviors in rats by unilateral plantar incision. Thermal hyperalgesia and mechanical allodynia were measured by using a radiant heat and electronic Von Frey filament, respectively. Expression of motilin in hippocampus, stomach, duodenum, and plasmawas determined by ELISA; and expression of motilin receptor in hippocampus was detected by western blot assay.Motilin and its receptor were detected in hippocampus. Acute incisional pain increased motilin expression in hippocampus and duodenum, while decreasing its expression in gastric body and plasma. Postoperative analgesia with morphine+fentanyl upregulated the expression of motilin in hippocampus; however, motilin was downregulated in peripheral sites. Naloxone at 1ng/kg restored motilin to baseline levels. Acute pain, morphine+fentanyl, and naloxone all induced the expression of motilin receptor in hippocampus.Acute pain, postoperative analgesia with opioids, and naloxone significantly impacted the expression of hippocampal and peripheral motilin. Variation trends in all sites were not identical. Intrathecal injection of low-dose naloxone upregulated paw withdrawal thermal latency and enhanced the analgesic effects of opioids. The findings presented here provide a new basis for central and peripheral regulation in GI motility, clinical postoperative analgesia, and management of analgesic complications.
- Unexpected Variation of the Codeine/Morphine Ratio Following Fatal Heroin Overdose. [JOURNAL ARTICLE]
- J Anal Toxicol 2014 Apr 11.
Postmortem samples from 14 cases of suspected heroin overdose were subjected to a preliminary systematic toxicological analysis in order to highlight the presence of unknown exogenous compounds (e.g., drugs of abuse, alcohol) that may have played a role in the mechanism of death. This analysis unveiled histories of poly-drug use in seven of the cases under investigation. Moreover, the concentrations of morphine and codeine in the brain were also investigated, and the results were compared with the data obtained from the blood specimens. The concentration of morphine in blood ranged from 33 to 688 ng/mL, while the concentration of codeine ranged from 0 to 193 ng/mL. However, in the brain, the concentration of morphine was found to be between 85 and 396 ng/g, while the levels of codeine ranged from 11 to 160 ng/g. The codeine/morphine ratio in the blood ranged from 0.043 to 0.619; however, in the brain, the same ratio was found to be between 0.129 and 0.552. In most cases, a significantly higher codeine/morphine ratio was found in the brain, suggesting the accumulation of codeine in brain tissue due its high lipophilicity as compared with morphine.
- Effects of Peritoneal Ropivacaine Nebulization for Pain Control After Laparoscopic Gynecologic Surgery. [JOURNAL ARTICLE]
- J Minim Invasive Gynecol 2014 Apr 8.
This trial evaluated the effects of peritoneal cold nebulization of ropivacaine on pain control after gynecologic laparoscopy.Evidence obtained from a properly designed, randomized, double-blind, placebo-controlled trial (Canadian Task Force classification I).San Gerardo Hospital of Monza, Italy, a tertiary care center.One hundred and thirty five adult women, ASA I-III, scheduled for operative laparoscopy.patients were randomized to receive either nebulization of ropivacaine 30 mg before surgery (PREOPERATIVE); nebulization of ropivacaine 30 mg after surgery (POSTOPERATIVE); instillation of ropivacaine 100 mg before surgery (INSTILLATION) or saline (CONTROL). Nebulization was performed using the Aeroneb Pro device (Aerogen, Galway, Ireland).Pain scores, morphine consumption, and ambulation time were collected in post anesthesia care unit and at 4, 6 and 24 hours, postoperatively. 118 patients completed the study. Patients in the PREOPERATIVE group referred lower pain Numeric Ranking Scale values compared with those in the CONTROL group (net difference 2 points, 95%CI 0.3 to 3.1 at 4 hours, 1 to 3 at 6 hours; and 0.7 to 3 at 24 hours, p=0.01) Patients in the PREOPERATIVE group consumed significantly less morphine than those in the CONTROL group (net difference 7 mg, 95%CI 0.7 to 13, p=0.02). Greater number of patients receiving nebulization walked without assistance within 12 hours after awakening than those in the INSTILLATION and CONTROL groups (net difference 15%, 95%CI 6 to 24%, p=0.001).Cold nebulization of ropivacaine before surgery reduced postoperative pain, morphine consumption, and was associated with earlier walking without assistance.
- Opioid/NMDA receptors blockade reverses the depressant-like behavior of foot shock stress in the mouse forced swimming test. [JOURNAL ARTICLE]
- Eur J Pharmacol 2014 Apr 10.
Opioid and glutamatergic receptors have a key role in depression following stress. In this study, we assessed opioid and glutamatergic receptors interaction with the depressant-like behavior of acute foot-shock stress in the mouse forced swimming test. Stress was induced by intermittent foot shock stimulation during 30minutes and swim periods were afterwards conducted by placing mice in separated glass cylinders filled with water for 6min. The immobility time during the last 4min of the test was considered. Acute foot-shock stress significantly increased the immobility time of mice compared to non-stressed control group (P≤0.01). Administration of non-selective opioid receptors antagonist, naltrexone (1 and 2mg/kg, i.p.), and the selective non-competitive NMDA receptor antagonist, MK-801 (0.05mg/kg, i.p.), and the selective serotonin reuptake inhibitor, fluoxetine (5mg/kg), significantly reduced the immobility time in stressed animals (P≤0.01). Lower doses of MK-801 (0.01mg/kg), naltrexone (0.3mg/kg), NMDA (75mg/kg) and morphine(5mg/kg) had no effect on foot-shock stressed mice. Combined treatment of sub-effective doses of naltrexone and MK-801 significantly showed an antidepressant-like effect (P≤0.001). On the other hand, co-administration of non-effective doses of NMDA and morphine with effective doses of naltrexone and MK-801 reversed the anti-immobility effect of these drugs. Taken together, we have for the first time demonstrated the possible role of opioid/NMDA receptors signaling in the depressant-like effect of foot-shock stress, and proposed the use of drugs that act like standard anti-depressants in stress-induced depression.
- The effect of prolonged exposure to morphine on canine cerebral 5-HT2A receptors measured with (123)I-R91150 SPECT. [JOURNAL ARTICLE]
- Eur Neuropsychopharmacol 2014 Mar 26.
Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20mg twice daily for 10 days) with (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (P≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system.
- Perioperative epidural analgesia in children undergoing major abdominal tumor surgery - a single center experience. [Journal Article]
- J Pediatr Surg 2014 Apr; 49(4):551-5.
The purpose of this study was to assess the use of continuous epidural analgesia in pediatric patients undergoing major abdominal tumor surgery.Children undergoing major abdominal tumor surgery at our institution between 2008 and 2012 (n=40) received continuous epidural analgesia via an epidural catheter. Surgical trauma scores, pain scores, and clinical data of the children were compared to a pair-matched historical control group operated on between 2002 and 2007 without epidural analgesia.Pain levels in the study group on day 1 and 3 after surgery were lower compared to the control group. The differences did, however, not reach statistical significance (p=0.15 and 0.09). Children in the study group received significantly fewer additional doses of piritramide or morphine (45% versus 82%, p<0.001). Despite significantly higher surgical trauma scores in the study group (p=0.018), there were no statistical differences regarding clinical parameters, such as mechanical ventilation time, time on intensive care unit, and total hospital stay. There were no catheter-related complications.Continuous epidural analgesia is beneficial for children undergoing complex abdominal tumor surgery with regard to pain levels, postoperative recovery, and general clinical course. Expertise of the managing team, a careful patient selection, and a continuous quality assessment are essential for success.
- No correlation between minimal electrical charge at the tip of the stimulating catheter and the efficacy of the peripheral nerve block catheter for brachial plexus block: a prospective blinded cohort study. [JOURNAL ARTICLE]
- BMC Anesthesiol 2014 Apr 11; 14(1):26.
Stimulating catheters offer the possibility of delivering an electrical charge via the tip of the catheter. This may be advantageous as it allows verifying if the catheter tip is in close proximity to the target nerve, thereby increasing catheter performance. This prospective blinded cohort study was designed to investigate whether there is a correlation between the minimal electrical charge at the tip of the stimulating catheter, and the efficacy of the peripheral nerve block (PNB) catheter as determined by 24 h postoperative morphine consumption.Forty adult patients with ASA physical health classification I-III scheduled for upper extremity surgery under combined continuous interscalene block and general anesthesia were studied. Six patients were excluded from analysis.After inserting a stimulating catheter as if it were a non-stimulating catheter for 2-5 cm through the needle, the minimal electrical charge necessary to obtain an appropriate motor response was determined. A loading dose of 20 mL 0.75% ropivacaine was then administered, and postoperative analgesia was provided by a continuous infusion of ropivacaine 0.2% 8 mL.h-1 via the brachial plexus catheter, and an intravenous morphine patient-controlled analgesia (PCA) device.Main outcome measures include the minimal electrical charge (MEC) at the tip of the stimulating catheter necessary to elicit an appropriate motor response, and the efficacy of the PNB catheter as determined by 24 h postoperative PCA morphine consumption.Mean (SD) [range] MEC at the tip of the stimulating catheter was 589 (1414) [30 - 5000] nC. Mean (SD) [range] 24 h morphine consumption was 8.9 (9.9) [0-29] mg. The correlation between the MEC and 24 h postoperative morphine consumption was Spearman's Rho rs = -0.26, 95% CI -0.56 to 0.09.We conclude that there is no proportional relation between MEC at the tip of the blindly inserted stimulating catheter and 24 h postoperative morphine consumption.Trial registration: Trialregister.nl identifier: NTR2328.
- Safety and accuracy of robot-assisted versus fluoroscopy-guided pedicle screw insertion for degenerative diseases of the lumbar spine: a matched cohort comparison. [JOURNAL ARTICLE]
- J Neurosurg Spine 2014 Apr 11.
Object Recent years have been marked by efforts to improve the quality and safety of pedicle screw placement in spinal instrumentation. The aim of the present study is to compare the accuracy of the SpineAssist robot system with conventional fluoroscopy-guided pedicle screw placement. Methods Ninety-five patients suffering from degenerative disease and requiring elective lumbar instrumentation were included in the study. The robot cohort (Group I; 55 patients, 244 screws) consisted of an initial open robot-assisted subgroup (Subgroup IA; 17 patients, 83 screws) and a percutaneous cohort (Subgroup IB, 38 patients, 161 screws). In these groups, pedicle screws were placed under robotic guidance and lateral fluoroscopic control. In the fluoroscopy-guided cohort (Group II; 40 patients, 163 screws) screws were inserted using anatomical landmarks and lateral fluoroscopic guidance. The primary outcome measure was accuracy of screw placement on the Gertzbein-Robbins scale (Grade A to E and R [revised]). Secondary parameters were duration of surgery, blood loss, cumulative morphine, and length of stay. Results In the robot group (Group I), a perfect trajectory (A) was observed in 204 screws (83.6%). The remaining screws were graded B (n = 19 [7.8%]), C (n = 9 [3.7%]), D (n = 4 [1.6%]), E (n = 2 [0.8%]), and R (n = 6 [2.5%]). In the fluoroscopy-guided group (Group II), a completely intrapedicular course graded A was found in 79.8% (n = 130). The remaining screws were graded B (n = 12 [7.4%]), C (n = 10 [6.1%]), D (n = 6 [3.7%]), and E (n = 5 [3.1%]). The comparison of "clinically acceptable" (that is, A and B screws) was neither different between groups (I vs II [p = 0.19]) nor subgroups (Subgroup IA vs IB [p = 0.81]; Subgroup IA vs Group II [p = 0.53]; Subgroup IB vs Group II [p = 0.20]). Blood loss was lower in the robot-assisted group than in the fluoroscopy-guided group, while duration of surgery, length of stay, and cumulative morphine dose were not statistically different. Conclusions Robot-guided pedicle screw placement is a safe and useful tool for assisting spine surgeons in degenerative spine cases. Nonetheless, technical difficulties remain and fluoroscopy backup is advocated.
- Epidemiological trends and the advances of treatments of amphetamine-type stimulants (ATS) in China. [Journal Article]
- Am J Addict 2014 May; 23(3):313-7.
Amphetamine-type stimulants (ATS) have quickly spread and been widely abused in many parts of the world, particularly in China. This review focuses on and describes the epidemiological trends and the advances of treatments of ATS in China.A descriptive study based on literature identified from searches of the China National Knowledge Infrastructure (1979-2013), PubMed databases, hand-picked references, and online references with emphasis on epidemiology, treatment and traditional Chinese medicine. This review covers some traditional Chinese treatments and their complementary Western approaches.The epidemiological trends of ATS in China have led to its being 2.2 times the rate of morphine abuse and second only to marijuana abuse. The treatment programs in China have used traditional herbal approaches as well as acupuncture, often in combination with Western medications such as fluoxetine for depression associated with ATS abuse. Other herbal treatments have reversed the cardiac arrhythmias associated with ATS intoxication, and acupuncture has been used successfully for the protracted depressive and somatic symptoms of ATS withdrawal over a period of 3 months.These traditional Chinese treatments may be increasingly available to the world, but will remain a consistent complementary therapy for ATS in China and the Far East, where ATS has become such a prevalent problem. (Am J Addict 2014;23:313-317).
- High levels of opioid analgesic co-prescription among methadone maintenance treatment clients in British Columbia, Canada: Results from a population-level retrospective cohort study. [Journal Article]
- Am J Addict 2014 May; 23(3):257-64.
The non-medical use of prescription opioids (PO) has increased dramatically in North America. Special consideration for PO prescription is required for individuals in methadone maintenance treatment (MMT). Our objective is to describe the prevalence and correlates of PO use among British Columbia (BC) MMT clients from 1996 to 2007.This study was based on a linked, population-level medication dispensation database. All individuals receiving 30 days of continuous MMT for opioid dependence were included in the study. Key measurements included the proportion of clients receiving >7 days of a PO other than methadone during MMT from 1996 to 2007. Factors independently associated with PO co-prescription during MMT were assessed using generalized linear mixed effects regression.16,248 individuals with 27,919 MMT episodes at least 30 days in duration were identified for the study period. Among them, 5,552 individuals (34.2%) received a total of 290,543 PO co-prescriptions during MMT. The majority (74.3%) of all PO dispensations >7 days originated from non-MMT physicians. The number of PO prescriptions per person-year nearly doubled between 1996 and 2006, driven by increases in morphine, hydromorphone and oxycodone dispensations. PO co-prescription was positively associated with female gender, older age, higher levels of medical co-morbidity as well as higher MMT dosage, adherence, and retention.A large proportion of MMT clients in BC received co-occurring PO prescriptions, often from physicians and pharmacies not delivering MMT. Experimental evidence for the treatment of pain in MMT clients is required to guide clinical practice. (Am J Addict 2014;23:257-264).