Inadequate pain relief after lower limb joint replacement surgery has been a well-recognised limiting factor affecting post-operative mobilisation and length of hospital stay. Multimodal local wound infiltration with local anaesthetics, adrenaline and non-steroidal anti-inflammatory agents can lower the opiate intake, reduce the length of stay and enhance early mobilisation in knee replacement patients. A retrospective review of 64 patients undergoing primary total knee replacement was undertaken. Thirty-two patients (cases) had their wounds infiltrated with ropivacaine, adrenaline and ketorolac by the operating surgeon, intraoperatively. Subsequently, a 19G wound catheter placed into the knee joint. They received two further top-up doses of the same combination at 10 and 20 h post-operatively. This group was compared with a control group of 32 patients who did not receive any local infiltration. Both groups were comparable in terms of BMI and age. Post-operative opiate drug consumption in first 48 h after surgery, length of hospital stays and time taken to mobilise after surgery were recorded. There was significant reduction in opiate consumption in the treatment group with an average consumption of 49.35 mg of morphine compared to 71.48 mg in the control group (p = 0.004). The median length of hospital stay was significantly reduced from 5 days in the control group to 4 days in the treatment group (p = 0.03). The patients in the treatment group mobilised around 19 h earlier (p = 0.001). No major post-operative complications were encountered in either group. Wound infiltration is an effective and safe technique that promotes early rehabilitation and discharge of patients following primary total knee replacement.

Opioid prescribing for chronic noncancer pain is increasing, but there is limited knowledge about longer-term outcomes of people receiving opioids for conditions such as back pain. This study aimed to explore the relationship between prescribed opioids and disability among patients consulting in primary care with back pain. A total of 715 participants from a prospective cohort study, who gave consent for review of medical and prescribing records and completed baseline and 6month follow-up questionnaires, were included. Opioid prescription data were obtained from electronic prescribing records, and morphine equivalent doses were calculated. The primary outcome was disability (Roland-Morris Disability Questionnaire [RMDQ]) at 6months. Multivariable linear regression was used to examine the association between opioid prescription at baseline and RMDQ score at 6months. Analyses were adjusted for potential confounders using propensity scores reflecting the probability of opioid prescription given baseline characteristics. In the baseline period, 234 participants (32.7%) were prescribed opioids. In the final multivariable analysis, opioid prescription at baseline was significantly associated with higher disability at 6-month follow-up (P<.022), but the magnitude of this effect was small, with a mean RMDQ score of 1.18 (95% confidence interval: 0.17 to 2.19) points higher among those prescribed opioids compared to those who were not. Our findings indicate that even after adjusting for a substantial number of potential confounders, opioids were associated with slightly worse functioning in back pain patients at 6-month follow-up. Further research may help us to understand the mechanisms underlying these findings and inform clinical decisions regarding the usefulness of opioids for back pain.

BACKGROUND:

The quantification of pain intensity in vivo is essential for identifying the mechanisms of various types of pain or for evaluating the effects of different analgesics. A variety of behavioral tests for pain measurement have been devised, but many are limited because animals are physically restricted, which affects pain sensation. In this study, pain assessment was attempted with minimal physical restriction, and voluntary movements of unrestrained animals were used to evaluate the intensities of various types of pain.

RESULTS:

The number of times animals reared or total distances traveled was measured using a motion-tracking device and found to be markedly reduced in carrageenan-induced inflammatory, acetic acid-induced visceral, and streptozotocin-induced neuropathic pain tests. These two voluntary movement parameters were found to be highly correlated with paw withdrawal latency from irradiating heat. In addition, these parameters were markedly reversed by morphine and by non-steroidal anti-inflammatory drugs in inflammatory pain models. These parameters were also useful to detect hypoalgesia in TRPV1-/- mice.

CONCLUSIONS:

These results suggest that parameters of voluntary movement, such as, number of rearing and total distance moved, are effective indicators of pain intensity for many types of pain and that they can be used to evaluate degree of pain perception.

PURPOSE:

To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms.

METHODS:

A total of 109 patients treated with morphine were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT, OPRM1 and UGT2B7 genes. The plasma concentration of morphine and of M3G/M6G metabolites were evaluated by means of reversed phase high-performance liquid chromatography coupled with mass spectrometry.

RESULTS:

An association between average morphine consumption during the first 24 postoperative hours by patient-controlled analgesia (PCA) and COMT haplotypes was found. Specifically, patients with the diplotype for average pain intensity (APS/APS) required the lowest morphine doses compared to the other subjects (p = 0.011). The APS haplotype contains an adenine corresponding to methionine, instead of valine, at position 158 of the COMT protein. Met/Met homozygous patients consumed significantly lower morphine doses than other subjects (p = 0.014); accordingly, Val158Met genotyping alone might be used in the clinical setting to predict PCA morphine need. Considering both COMT Val158Met and OPRM1 A118G polymorphisms, carriers of both the Met/Met and AA genotypes required less morphine than other subjects, although the difference was not significant. The analysis of UGT2B7 revealed the occurrence of two common haplotypes (G_C_C_A_C and A_T_T_G_T) that did not prove to be related with plasma morphine and M3G/M6G concentration.

CONCLUSIONS:

By considering COMT, OPRM1, and UGT2B7 genotypes, as well as pharmacokinetic results, only COMT polymorphisms appear to be predictive of morphine need in postoperative pain therapy.

The anticonvulsant effects of agmatine, an endogenous polyamine and a metabolite of L-arginine, have been shown in various experimental seizure models. Agmatine also potentiates the anti-seizure activity of morphine. The present study aimed to investigate a possible involvement of nitric oxide (NO) pathway in the protection by agmatine and morphine co-administration against pentylenetetrazole (PTZ) -induced seizure in male mice. To this end, the thresholds for the clonic seizures induced by the intravenous administration of PTZ, a GABA antagonist, were assessed. Intraperitoneal administration of morphine at lower dose (1mg/kg) increased the seizure threshold. Also intraperitoneal administration of agmatine (5 and 10mg/kg) increased the seizure threshold significantly. Combination of subeffective doses of morphine and agmatine led to potent anticonvulsant effects. Non-effective doses of morphine (0.1 and 0.5mg/kg) were able to induce anticonvulsant effects in mice pretreated with agmatine (3mg/kg). Concomitant administration of either the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (1, 5mg/kg, i.p.) or the selective NOS inhibitor 7-NI (15, 30mg/kg, i.p.), with an ineffective combination of morphine (0.1mg/kg) plus agmatine (1mg/kg) produced significant anticonvulsant impacts. Moreover, the NO precursor, L-arginine (30, 60mg/kg, i.p.), inhibited the anticonvulsant action of agmatine (3mg/kg) plus morphine (0.5mg/kg) co-administration. Our results indicate that pretreatment of animals with agmatine enhances the anticonvulsant effects of morphine via a mechanism which may involve the NO pathway.

STUDY OBJECTIVE:

To determine the risk factors of perioperative complications and the impact of intrathecal morphine (ITM) in major vascular surgery.

DESIGN:

Retrospective analysis of a prospective cohort. SETTINGS: Operating room, intensive care unit, and Postanesthesia Care Unit of a university hospital.

MEASUREMENTS:

Data from 595 consecutive patients who underwent open abdominal aortic surgery between January 1997 and December 2011 were reviewed. Data were stratified into three groups based on the analgesia technique delivered: systemic analgesia (Goup SA), thoracic epidural analgesia (Group TEA), and intrathecal morphine (Group ITM). Preoperative patient characteristics, perioperative anesthetic and medical interventions, and major nonsurgical complications were recorded.

MAIN RESULTS:

Patients managed with ITM (n=248) and those given thoracic epidural analgesia (n=70) required lower doses of intravenous (IV) sufentanil intraoperatively and were extubated sooner than those who received systemic analgesia (n=270). Total inhospital mortality was 2.9%, and 24.4% of patients experienced at least one major complication during their hospital stay. Intrathecal morphine was associated with a lower risk of postoperative morbidity (OR 0.51, 95% CI 0.28 - 0.89), particularly pulmonary complications (OR 0.54, 95% CI 0.31 - 0.93) and renal dysfunction (OR 0.52, 95% CI 0.29 - 0.97). Other predictors of nonsurgical complications were ASA physical status 3 and 4 (OR 1.94, 95% CI 1.07 - 3.52), preoperative renal dysfunction (OR 1.61, 95% CI 1.01 - 2.58), prolonged surgical time (OR 1.78, 95% CI 1.16 - 2.78), and the need for blood transfusion (OR 1.77, 95% CI 1.05 - 2.99).

CONCLUSION:

This single-center study showed a decreased risk of major nonsurgical complications in patients who received neuraxial analgesia after abdominal aortic surgery.

Neuropeptide S (NPS) is a newly identified ligand for the previously discovered G-protein coupled receptor 154 now named NPSR. Recently, it has been found that NPSR gene expression is altered during ethanol withdrawal. In this study we tried to elucidate if NPSR gene expression is modified in response to morphine withdrawal and its protracted abstinence. To induce opioid dependence Wistar rats were treated for seven days with morphine. Twelve hours and 7 days after the last morphine administration brains were removed and the expression of NPSR mRNA was analyzed by in situ hybridization (ISH). Succesful induction of opioid dependence was confirmed by the naloxone-precipitated withdrawal test 2hours after the last morphine administration. Moreover, 7 days after the last morphine dose animals were checked for signs of anxiety and for intracerebroventricular (ICV) NPS (0.3 and 1.0 nmol) induced anxiolytic effects by elevated plus maze (EPM). Results showed that in morphine treated rats strong somatic signs of naloxone-precipated withdrawal occurred. ISH data revealed changes in NPSR gene expression in the ventral tegmental area as well as in the basolateral amygdaloid and bed nucleus of stria terminalis at 12hours and 7 days into abstinence, respectively. At seven days into abstinence post dependent animals showed higher levels of anxiety than controls which were significantly attenuated by NPS. These results demonstrated that morphine dependence induction led to i) changes in NPSR mRNA expression; ii) increased anxiety; iii) more potent anxiolytic-like effect of NPS.

BACKGROUND/PURPOSE:

In a recent study, we found that baicalin exhibited a potent analgesic effect on carrageenan-evoked thermal hyperalgesia. The underlining mechanisms may be associated with inhibition of inflammatory mediator overproduction, including proinflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). In the present study, we examined the effect of baicalin on the antinociceptive effect of morphine and histone deacetylase 1 (HDAC1) expression in the spinal cord dorsal horn in neuropathic pain rats.

METHODS:

Neuropathic pain was induced by tight ligation of the left L5 spinal nerve of the rats. An intrathecal catheter was implanted for drug administration. Nociception was assessed by using the plantar test with the Hargreaves radiant heat apparatus, and the von Frey test with the dynamic plantar anesthesiometer. Spinal cords were removed for histone acetyl-H3 and HDAC1 western blot analysis at the end of the nociceptive assessment.

RESULTS:

The results showed that hyperalgesia and allodynia were observed in the spinal nerve ligated (SNL) left hindlimb; it was companied by histone-H3 deacetylation and HDAC1 overexpression on the ipsilateral side of the spinal cord dorsal horn. Intrathecal injection of baicalin (10 μg) significantly attenuated the allodynia and hyperalgesia, and enhanced the antinociceptive effect of morphine (15 μg). Moreover, baicalin reversed the histone-H3 acetylation and suppressed HDAC1 expression on the ipsilateral side of the spinal cord dorsal horn of SNL rats.

CONCLUSION:

The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.

Kinsbourne syndrome is a rare neurological disorder that primarily affects children previously healthy and aged between 6 and 36 months. It is characterized by opsoclonus (rapid, irregular, horizontal and vertical eye movements) and myoclonus that may affect trunk, limbs or face, and cerebellar ataxia. It may be considered a paraneoplastic syndrome by association with neuroblastomas, hepatoblastomas and, rarely, ganglioneuromas. The aim of this paper was to present the most relevant aspects of Kinsbourne syndrome, as well as the technique used for resection of mediastinal tumor in a child with this syndrome.Child, 1 year and 5 months, with a diagnosis of posterior mediastinal tumor and Kinsbourne syndrome. Premedicated with oral midazolam. Anesthesia induced with sevofl urane, nitrous oxide, fentanyl, and rocuronium. Maintenance of anesthesia with sevofl urane, nitrous oxide, fentanyl, and rocuronium. Neuromuscular block reversal with neostigmine combined with atropine. Postoperative analgesia with the use of dipyrone, morphine, and ketoprofen. Taken to the intensive care unit extubated, with stable hemodynamic and respiratory parameters. ICU discharge four days after surgery and hospital discharged on the seventh postoperative day without complications. Anatomopathological examination revealed ganglioneuroblastoma.Kinsbourne syndrome is a rare neurological disorder. The drugs used in our patient proved safe and allowed an uneventful anesthesia. Drugs that trigger or aggravate opsoclonus and myoclonus, such as ketamine and etomidate, should be avoided in these patients.

A statistical tool equipped with Plackett-Burman design (PBD) and central composite design (CCD) was used for fast stacking analysis of ten frequently consumed drugs, namely codeine, morphine, methamphetamine, ketamine, alprazolam, clonazepam, diazepam, flunitrazepam, nitrazepam and oxazepam, by capillary electrophoresis (CE). This statistical design is expected to help quick analysis with few procedures, avoiding tedious work required because of the large number of variables or parameters. A large volume sample stacking (LVSS)-sweeping CE is developed for concentrating and analyzing the 10 abused drugs. First, phosphate buffer (50mM, pH 2.3) containing methanol was filled into a capillary and then the extracted urine sample was loaded (1psi, 200s) to enhance sensitivity. The sweeping and separating steps were completed simultaneously by phosphate buffer (50mM, pH 2.3) containing methanol and sodium dodecyl sulfate, within 15min. Better resolution was obtained by the experimental design than the "one factor at a time" (OFAT) approach. During method validation, calibration plots were linear (r>0.998), over a range of 25-1500ng/mL for the six benzodiazepines, methamphetamine and ketamine, and 50-3000ng/mL for codeine and morphine. The RSD of precision and absolute RE of accuracy in intra-day and inter-day assays were below 14.54% and 16.61%, respectively. The minimum limits for detection (S/N=3) of analytes were in the range of 7.5-30ng/mL. This stacking method increased sensitivity more than 200-fold and can be applied for detection of the presence of methamphetamine in an abuser's urine (3600ng/mL), which was confirmed by GC-MS. The method is considered feasible for fast screening of abused drugs in urine.