The anticonvulsant gabapentin, proven effective for neuropathic pain in two large, placebo-controlled clinical trials, is widely used for treatment of chronic pain. Preclinical studies have ...demonstrated analgesic and antiallodynic effects in models involving neuronal sensitization and nerve injury, without affecting acute pain transmission. The aim of the present study was to link data from animal models and clinical trials for chronic pain by investigating the effect of gabapentin on acute nociception and experimentally induced cutaneous hyperalgesia in healthy volunteers.
The human experimental hyperalgesia model, the heat-capsaicin sensitization model, was induced in 25 healthy male volunteers. Subjects received oral gabapentin (1,200 mg) or placebo after heat-capsaicin sensitization was established on the forearm. The primary outcome measures were the sizes of the areas of secondary hyperalgesia to von Frey hair and brush stimulation on the forearm. Secondary outcome measures were as follows: (1) size of secondary hyperalgesia area in response to brief thermal sensitization procedure on the thigh; (2) heat pain detection thresholds in normal and sensitized skin; and (3) painfulness of 1 min of 45 degrees C stimulation in normal skin.
Oral gabapentin profoundly suppressed established cutaneous sensitization on the forearm and prevented development of cutaneous sensitization on the thigh. Thermal nociception in normal skin was unchanged. Side effects were modest.
The results link preclinical findings with results from clinical trials of neuropathic pain. The results further suggest that gabapentin may prove effective in acute pain disorders involving neuronal sensitization, such as postoperative pain and acute herpetic pain, and could prove effective in prevention of chronic pain.
This study examines important developmental differences in patterns of activation in the prefrontal cortex during performance of a Go-No-Go paradigm using functional magnetic resonance imaging ...(fMRI). Eighteen subjects (9 children and 9 adults) were scanned using gradient echo, echo planar imaging during performance of a response inhibition task. The results suggest four general findings. First, the location of activation in the prefrontal cortex was not different between children and adults, which is similar to our earlier pediatric fMRI results of prefrontal activation during a working memory task (Casey et al., 1995). Second, the volume of activation was significantly greater for children relative to adults. These differences in volume of activation were observed predominantly in the dorsal and lateral prefrontal cortices. Third, although inhibitory processes have typically been associated with more ventral or orbital frontal regions, the current study revealed activation that was distributed across both dorsolateral and orbitofrontal cortices. Finally, consistent with animal and human lesion studies, activity in orbital frontal and anterior cingulate cortices correlated with behavioral performance (i.e., number of false alarms). These results further demonstrate the utility of this methodology in studying pediatric populations.
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was investigated at the velocity filter SHIP at GSI, Darmstadt, with the intention to study production and decay properties of isotopes of element 120. Three ...correlated signals were measured, which occurred within a period of 279ms. The heights of the signals correspond with the expectations for a decay sequence starting with an isotope of element 120. However, a complete decay chain cannot be established, since a signal from the implantation of the evaporation residue cannot be identified unambiguously. Measured properties of the event chain are discussed in detail. The result is compared with theoretical predictions. Previously measured decay properties of even element super-heavy nuclei were compiled in order to find arguments for an assignment from the systematics of experimental data. In the course of this review, a few tentatively assigned data could be corrected. New interpretations are given for results which could not be assigned definitely in previous studies. The discussion revealed that the cross-section for production of element 120 could be high enough so that a successful experiment seems possible with presently available techniques. However, a continuation of the experiment at SHIP for a necessary confirmation of the results obtained in a relatively short irradiation of five weeks is not possible at GSI presently. Therefore, we decided to publish the results of the measurement and of the review as they exist now. In the summary and outlook section we also present concepts for the continuation of research in the field of super-heavy nuclei.
Background: We have reviewed opioid‐related adverse events in studies of opioid sparing with cyclooxygenase‐2 (COX‐2) inhibitors compared with placebo in postoperative pain.
Methods: Randomized, ...controlled trials were evaluated. Outcome measures were significant reduction in consumption of supplementary opioids with the COX‐2 inhibitors and reported opioid‐related adverse events (nausea, vomiting, constipation, dizziness, sedation, pruritus and/or urinary retention) 0–24 h after surgery.
Results: Nineteen studies including 26 comparisons of four COX‐2 inhibitors (rofecoxib, celecoxib, parecoxib and valdecoxib) were evaluated, in which significant opioid‐sparing averaging about 35% with COX‐2 inhibitors and opioid‐related adverse events were reported. The trials were in general of high quality (median Oxford quality score 4) but the reporting quality of adverse events was poor. Opioid‐related adverse events, i.e. vomiting, constipation and pruritus, were only significantly reduced with COX‐2 inhibitors in four of the 26 comparisons. Quantitative analysis of combined data revealed a significantly reduced risk for only dizziness; the clinical relevance was minor as the number needed to treat (NNT) was about 33.
Conclusion: The limitation of this review is the lack of quality of data of adverse events from the original trials. Although supplementary opioid consumption in all trials was significantly reduced by on average 35% with the COX‐2 inhibitors, it was only sporadically possible to demonstrate a clinically important reduction in opioid‐related adverse events. Data did not support the common opinion that opioid‐sparing with COX‐2 inhibitors provides much clinical beneficial effect with respect to opioid‐related adverse events. Future studies have to increase the awareness and proper reporting of adverse events in the postoperative period.
Background
The analgesic effect of the adductor canal block (ACB) after knee surgery has been evaluated in a number of trials. We hypothesized that the ACB would provide substantial pain relief to ...patients responding with moderate to severe pain after arthroscopic knee surgery.
Methods
Fifty subjects with moderate to severe pain after arthroscopic knee surgery were enrolled in this placebo‐controlled, blinded trial. All subjects received two ACBs; an initial ACB with either 30 ml ropivacaine 7.5 mg/ml (n = 25) (R group) or saline (n = 25) (C group) and after 45 min a second ACB with the opposite study medication, according to randomization. Primary outcome was pain during 45 degrees active flexion of the knee at 45 min after the first block, assessed on a 0–100 mm visual analogue scale. Secondary outcome measures were: pain at rest and during flexion of the knee, worst pain experienced during a 5‐m walk, patient's evaluation of muscle strength during walk, and amount of sufentanil administered during the 90‐min study period.
Results
Regarding primary outcome, mean pain score difference between groups was 34 (95% CI: 25 to 44) mm, P < 0.001, in favour of the R group. At rest, mean pain score difference was 32 (23 to 41) mm, P < 0.001, and during walk: 21 (6 to 36) mm, P = 0.01 in favour of the R group. There were no differences between groups regarding other secondary outcome measures.
Conclusion
The ACB is a relevant option for patients with moderate to severe pain after arthroscopic knee surgery.
Background
The association between pain and psychological characteristics has been widely debated. Thus, it remains unclear whether an individual's psychological profile influences a particular pain ...experience, or if previous pain experience contributes to a certain psychological profile. Translational studies performed in healthy volunteers may provide knowledge concerning psychological factors in healthy individuals as well as basic pain physiology. The aim of this review was to investigate whether psychological vulnerability or specific psychological variables in healthy volunteers are predictive of the level of pain following experimental pain models.
Methods
A systematic search on the databases, PubMed, Embase, Cochcrane library, and Clinicaltrials.gov was performed during September 2014. All trials investigating the association between psychological variables and experimental pain in healthy volunteers were considered for inclusion.
Results
Twenty‐nine trials met the inclusion criteria, with a total of 2637 healthy volunteers. The included trials investigated a total of 45 different psychological tests and 27 different types of pain models. The retrieved trials did not present a sufficiently homogenous group to perform meta‐analysis. The collected results were diverse. A total of 16 trials suggested that psychological factors may predict the level of pain, seven studies found divergent results, and six studies found no significant association between psychological variables and experimental pain.
Conclusion
Psychological factors may have predictive value when investigating experimental pain. However, due to substantial heterogeneity and methodological shortcomings of the published literature, firm conclusions are not possible.
Background
The number of surgical procedures is increasing, and knowledge of surgical risk factors, post‐operative mortality and serious adverse events (SAE) is essential. The aim with our study was ...to determine the risk of a composite outcome of post‐operative: death; myocardial infarction; pulmonary embolism; stroke; gastrointestinal bleeding; dialysis or reoperation.
Methods
Data of surgical procedures in the period from January 1, 2012 to June 30, 2012 were retrieved from the Danish Anaesthesia Database (DAD). Follow‐up of all patients undergoing hip or knee replacement, abdominal or gynaecological surgery was conducted retrieving data from The Danish Civil Registration System and the National Patient Register. Total observation time was from January 1, 2012 to June 6, 2013.
Results
A total7449 adult patients were included in the final analysis. The risk of the composite outcome during a follow‐up until 342 days after inclusion of the last patient was estimated to 8.3%, 95% Confidence Intervals (CI) (7.8–9.0), with a median observation time of 437 days (IQR 387–485, range 0–522). The risk of the composite outcome within 90‐ and 180‐day follow‐up of each patient was 4.8% (4.4–5.3) and 5.9% (5.4–6.5), respectively. Mortality within longest follow‐up as well as 90 and 180 days post‐operatively was 3.6% (3.1–4.0), 1.7% (1.4–2.0), and 2.2% (1.9–2.6), respectively.
Conclusion
We found a risk of one or more events in the composite outcome within 342 days after inclusion of the last patients of 8.3% (7.8–9.0). The results are applicable in estimations of adequate sample sizes in future clinical trials investigating effects of interventions on SAEs.
The relative importance of different nociceptive mechanisms for the intensity, duration, and character of postoperative pain is not well established. It has been suggested that sensitization of ...dorsal horn neurones may contribute to pain in the postoperative period. We hypothesized that wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia share a common mechanism, sensitization of central neurones, and consequently, that the short-acting opioid remifentanil would have comparable effects on hyperalgesia in both conditions.
In a randomized, controlled, double-blind trial, we assessed mechanical hyperalgesia in skin bordering the surgical wound, and an area of experimentally heat-induced secondary hyperalgesia on the thigh, in 12 patients who underwent abdominal hysterectomy within 5 days prior to the investigation. Observations were made before and during a drug challenge with remifentanil, which has been demonstrated to reduce the area of heat-induced secondary hyperalgesia in volunteers.
The area of skin with surgically-induced mechanical hyperalgesia, the area of heat-induced secondary hyperalgesia, and pain during cough, were significantly reduced during remifentanil infusion compared with placebo (P = 0.008, P = 0.006, and P = 0.002, respectively). The relative reduction (% of baseline) of the area of skin with surgically-induced hyperalgesia and heat-induced secondary hyperalgesia during infusion of remifentanil was significantly associated (R2 = 0.72, P = 0.001).
Although remifentanil is not a highly targeted "antihyperalgesic," these results support the hypothesis that both wound hyperalgesia in postoperative patients and experimentally heat-induced secondary hyperalgesia may share common mechanisms, and that central neuronal sensitization may contribute to some aspects of postoperative pain. Antihyperalgesic drugs should be further developed and evaluated in clinical trials of postoperative pain.
Background
Adductor‐canal‐blockade is a new technique for pain relief after knee surgery. This block could cause nerve injury and the aim of this follow‐up study was to determine the prevalence of ...saphenous nerve injury in patients receiving adductor‐canal‐blockade for pain treatment after total knee arthroplasty.
Methods
All patients included in two former studies of adductor‐canal‐blockade following total knee arthroplasty were invited to participate in this follow‐up study 3–6 months after surgery. We examined the cutaneous area on the medial aspect of the lower leg (medial crural branch of the saphenous nerve), as well as the anterior, posterior, lateral and infrapatellar part of the affected and contralateral lower leg. Sensory function was tested with pinprick (sharp and blunt needle), temperature discrimination (cold disinfectant swabs) and light brush.
Results
We included 97 patients. None of the patients 0–5.3% (99% confidence interval) had sensory changes related to temperature or light brush corresponding to the medial crural branch of the saphenous nerve, but 10 patients could not discriminate between blunt and sharp stimulation with a needle. In the infrapatellar area of the operated knee, 76 patients could not discriminate between blunt and sharp stimulation with a needle, 81 patients could not discriminate between cold and warmth, and 82 patients displayed an altered sensation to light brush.
Conclusion
We found no indications of saphenous nerve injury caused by the adductor‐canal‐blockade at the mid‐thigh level. However, 84% of the patients had signs of injury to the infrapatellar branch of the saphenous nerve in the operated leg. Such findings are well‐known complications to the surgical procedure.
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