Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room. For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief

Excitability of Aβ sensory neurons is altered in an animal model of peripheral neuropathy

<p>Abstract</p> <p>Background</p> <p>Causes of neuropathic pain following nerve injury remain unclear, limiting the development of mechanism-based therapeutic approaches. Animal models have provided some directions, but little is known about the specific sensory neurons that undergo changes in such a way as to induce and maintain activation of sensory pain pathways. Our previous studies implicated changes in the Aβ, normally non-nociceptive neurons in activating spinal nociceptive neurons in a cuff-induced animal model of neuropathic pain and the present study was directed specifically at determining any change in excitability of these neurons. Thus, the present study aimed at recording intracellularly from Aβ-fiber dorsal root ganglion (DRG) neurons and determining excitability of the peripheral receptive field, of the cell body and of the dorsal roots.</p> <p>Methods</p> <p>A peripheral neuropathy was induced in Sprague Dawley rats by inserting two thin polyethylene cuffs around the right sciatic nerve. All animals were confirmed to exhibit tactile hypersensitivity to von Frey filaments three weeks later, before the acute electrophysiological experiments. Under stable intracellular recording conditions neurons were classified functionally on the basis of their response to natural activation of their peripheral receptive field. In addition, conduction velocity of the dorsal roots, configuration of the action potential and rate of adaptation to stimulation were also criteria for classification. Excitability was measured as the threshold to activation of the peripheral receptive field, the response to intracellular injection of depolarizing current into the soma and the response to electrical stimulation of the dorsal roots.</p> <p>Results</p> <p>In control animals mechanical thresholds of all neurons were within normal ranges. Aβ DRG neurons in neuropathic rats demonstrated a mean mechanical threshold to receptive field stimulation that were significantly lower than in control rats, a prolonged discharge following this stimulation, a decreased activation threshold and a greater response to depolarizing current injection into the soma, as well as a longer refractory interval and delayed response to paired pulse electrical stimulation of the dorsal roots.</p> <p>Conclusions</p> <p>The present study has demonstrated changes in functionally classified Aβ low threshold and high threshold DRG neurons in a nerve intact animal model of peripheral neuropathy that demonstrates nociceptive responses to normally innocuous cutaneous stimuli, much the same as is observed in humans with neuropathic pain. We demonstrate further that the peripheral receptive fields of these neurons are more excitable, as are the somata. However, the dorsal roots exhibit a decrease in excitability. Thus, if these neurons participate in neuropathic pain this differential change in excitability may have implications in the peripheral drive that induces central sensitization, at least in animal models of peripheral neuropathic pain, and Aβ sensory neurons may thus contribute to allodynia and spontaneous pain following peripheral nerve injury in humans.</p

Dissociation of Motor Task-Induced Cortical Excitability and Pain Perception Changes in Healthy Volunteers

Background: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. Methodology/Principal Findings Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. Conclusions/Significance: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training

Systematic review on the recurrence of postoperative nausea and vomiting after a first episode in the recovery room – implications for the treatment of PONV and related clinical trials

BACKGROUND: Despite the presence of a plethora of publications on the prevention of postoperative nausea and vomiting (PONV) only little is known how to treat established symptoms. Besides the high effort of performing these efficacy trials (much more patients must give their consent than are actually included in a study) and ethical concerns, little is known about the rate of re-occurring PONV/vomiting after placebo. As a consequence investigators will have difficulties defining a clinically relevant effect for the new treatment which is crucial for any planning. A quantitative systematic review was performed in order to provide more reliable estimates of the incidence of re-occurring PONV/vomiting after placebo and to help investigators defining a clinically relevant treatment effect. METHODS: A systematic search of the literature was performed using an extended search strategy of a previous review. Data on the recurrence of PONV (any nausea or emetic symptom) and vomiting (retching or vomiting) was extracted from published reports treating PONV with placebo and unpublished results from two observational trials where no treatment was given. A nonlinear random effects model was used to calculate estimates of the recurrence of symptoms and their 95%-confidence intervals (95%-CI). RESULTS: A total of 29 trials (including the unpublished data) were eligible for the calculations. Depending on the length of observation after administering placebo or no treatment the recurrence rate of PONV was between 65% (95%-CI: 53%...75%) and 84% (95%-CI: 73%...91%) and that of vomiting was between 65% (95%-CI: 44%...81%) and 78% (95%-CI: 59%...90%). CONCLUSION: Almost all trials showed a considerable and consistently high rate of recurrence of emetic symptoms after placebo highlighting the need for a consequent antiemetic treatment. Future (placebo) controlled efficacy trials may use the presented empirical estimates for defining clinically relevant effects and for statistical power considerations

Computer work and musculoskeletal disorders of the neck and upper extremity: A systematic review

<p>Abstract</p> <p>Background</p> <p>This review examines the evidence for an association between computer work and neck and upper extremity disorders (except carpal tunnel syndrome).</p> <p>Methods</p> <p>A systematic critical review of studies of computer work and musculoskeletal disorders verified by a physical examination was performed.</p> <p>Results</p> <p>A total of 22 studies (26 articles) fulfilled the inclusion criteria. Results show limited evidence for a causal relationship between computer work per se, computer mouse and keyboard time related to a diagnosis of wrist tendonitis, and for an association between computer mouse time and forearm disorders. Limited evidence was also found for a causal relationship between computer work per se and computer mouse time related to tension neck syndrome, but the evidence for keyboard time was insufficient. Insufficient evidence was found for an association between other musculoskeletal diagnoses of the neck and upper extremities, including shoulder tendonitis and epicondylitis, and any aspect of computer work.</p> <p>Conclusions</p> <p>There is limited epidemiological evidence for an association between aspects of computer work and some of the clinical diagnoses studied. None of the evidence was considered as moderate or strong and there is a need for more and better documentation.</p

Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP

__Abstract__ Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This article describes the aims and design of a study to evaluate effects and costs of collaborative care with the antidepressant duloxetine for patients with pain symptoms and a depressive disorder, compared to collaborative care with placebo and compared to duloxetine alone

Hypnosis Antenatal Training for Childbirth (HATCh): a randomised controlled trial [NCT00282204]

BACKGROUND: Although medical interventions play an important role in preserving lives and maternal comfort they have become increasingly routine in normal childbirth. This may increase the risk of associated complications and a less satisfactory birth experience. Antenatal hypnosis is associated with a reduced need for pharmacological interventions during childbirth. This trial seeks to determine the efficacy or otherwise of antenatal group hypnosis preparation for childbirth in late pregnancy. METHODS/DESIGN: A single centre, randomised controlled trial using a 3 arm parallel group design in the largest tertiary maternity unit in South Australia. Group 1 participants receive antenatal hypnosis training in preparation for childbirth administered by a qualified hypnotherapist with the use of an audio compact disc on hypnosis for re-enforcement; Group 2 consists of antenatal hypnosis training in preparation for childbirth using an audio compact disc on hypnosis administered by a nurse with no training in hypnotherapy; Group 3 participants continue with their usual preparation for childbirth with no additional intervention. Women > 34 and < 39 weeks gestation, planning a vaginal birth, not in active labour, with a singleton, viable fetus of vertex presentation, are eligible to participate. Allocation concealment is achieved using telephone randomisation. Participants assigned to hypnosis groups commence hypnosis training as near as possible to 37 weeks gestation. Treatment allocations are concealed from treating obstetricians, anaesthetists, midwives and those personnel collecting and analysing data. Our sample size of 135 women/group gives the study 80% power to detect a clinically relevant fall of 20% in the number of women requiring pharmacological analgesia – the primary endpoint. We estimate that approximately 5–10% of women will deliver prior to receiving their allocated intervention. We plan to recruit 150 women/group and perform sequential interim analyses when 150 and 300 participants have been recruited. All participant data will be analysed, by a researcher blinded to treatment allocation, according to the "Intention to treat" principle with comprehensive pre-planned cost- benefit and subgroup analyses. DISCUSSION: If effective, hypnosis would be a simple, inexpensive way to improve the childbirth experience, reduce complications associated with pharmacological interventions, yield cost savings in maternity care, and this trial will provide evidence to guide clinical practice