Brain neuronal histamine, through its receptors, is involved in central pain perception. In the present study, the effect of microinjection of histamine, mepyramine (a histamine H(1) receptor antagonist) and ranitidine (a histamine H(2) receptor antagonist) into the dorsal hippocampus was investigated on a model of orofacial pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (1%, 50microl) in the upper lip in rats, and the time spent of face rubbing was measured in 3-min blocks for 45min. Formalin induced a marked biphasic (first phase: 0-3min; second phase: 15-33min) pain. Intra-hippocampal injection of histamine at doses of 0.25, 0.5microg attenuated the second phase, and at a dose of 1microg, histamine suppressed both phases of pain. Intra-hippocampal injections of mepyramine and ranitidine at the same doses of 1, 2 and 4microg produced no effects when used alone. Pretreatments with mepyramine and ranitidine at a same dose of 4microg prevented histamine (1microg)-induced antinociception. These results indicate that the activation of brain neuronal histamine at the levels of the hippocampus may produce antinociception. Hippocampal histamine-induced antinociception may be mediated thorough its H(1) and H(2) receptors.

CONTEXT: Co-occurring pain, fatigue, and sleep disturbance comprise a common symptom cluster in patients with cancer. Treatment approaches that target the cluster of symptoms rather than just a single symptom need to be identified and tested. OBJECTIVE: To synthesize evidence regarding mind-body interventions that have shown efficacy in treating two or more symptoms in the pain-fatigue-sleep disturbance cancer symptom cluster. METHODS: A literature search was conducted using CINAHL, Medline, and PsychInfo databases through March 2009. Studies were categorized based on the type of mind-body intervention (relaxation, imagery/hypnosis, cognitive-behavioral therapy/coping skills training [CBT/CST], meditation, music, and virtual reality), and a preliminary review was conducted with respect to efficacy for pain, fatigue, and sleep disturbance. Mind-body interventions were selected for review if there was evidence of efficacy for at least two of the three symptoms. Forty-three studies addressing five types of mind-body interventions met criteria and are summarized in this review. RESULTS: Imagery/hypnosis and CBT/CST interventions have produced improvement in all the three cancer-related symptoms individually: pain, fatigue, and sleep disturbance. Relaxation has resulted in improvements in pain and sleep disturbance. Meditation interventions have demonstrated beneficial effects on fatigue and sleep disturbance. Music interventions have demonstrated efficacy for pain and fatigue. No trials were found that tested the mind-body interventions specifically for the pain-fatigue-sleep disturbance symptom cluster. CONCLUSIONS: Efficacy studies are needed to test the impact of relaxation, imagery/hypnosis, CBT/CST, meditation, and music interventions in persons with cancer experiencing concurrent pain, fatigue, and sleep disturbance. These mind-body interventions could help patients manage all the symptoms in the cluster with a single treatment strategy.

OBJECTIVES: This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. METHODS: In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). RESULTS: The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. CONCLUSION: This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.

CONTEXT: Peripheral neuropathy is one of the most common complications of diabetes. OBJECTIVES: The purpose of this study was to evaluate the effects of photon stimulation on pain intensity, pain relief, pain qualities, and sensation and quality of life (QOL) in patients with painful diabetic peripheral neuropathy. METHODS: In this randomized, placebo-controlled trial, patients were assigned to receive either four photon stimulations (n=63) or four placebo (n=58) treatments. Pain intensity, pain relief, and pain qualities were assessed using self-report questionnaires. Sensation was evaluated using monofilament testing. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36). Multilevel regression model analyses were used to evaluate between-group differences in study outcomes. RESULTS: No differences, over time, in any pain intensity scores (i.e., pain intensity immediately posttreatment, average pain, worst pain) or pain relief scores were found between the placebo and treatment groups. However, significant decreases, over time, were found in some pain quality scores, and significant improvements in sensation were found in patients who received the photon stimulation compared with placebo. In addition, patients in the treatment group reported significant improvements in SF-36 social functioning and mental health scores. Findings from a responder analysis demonstrated that no differences were found in the percentages of patients in the placebo and treatment groups who received 30% or more or 50% or more reduction in pain scores immediately posttreatment. However, significant differences were found in the distribution of the changes in pain relief scores, with most of the patients in the photon stimulation group reporting a slight (28.6%) to moderate (34.9%) improvement in pain relief from the beginning to the end of the study compared with no change in pain relief (43.1%) in the placebo group. CONCLUSIONS: Four treatments with photon stimulation resulted in significant improvements in some pain qualities, sensation, and QOL outcomes in a sample of patients with a significant amount of pain and disability from their diabetes. A longer duration study is needed to further refine the photon stimulation treatment protocol in these chronically ill patients and to evaluate the sustainability of its effects.

CONTEXT: Persistent pain and sensory disturbances following surgical treatment for breast cancer is a significant clinical problem. The pathogenic mechanisms are complex and may be related to patient characteristics, surgical technique, and adjuvant therapy. OBJECTIVE: To examine prevalence of and factors associated with persistent pain after surgical treatment for breast cancer. Design, Setting, and PATIENTS: A nationwide cross-sectional questionnaire study of 3754 women aged 18 to 70 years who received surgery and adjuvant therapy (if indicated) for primary breast cancer in Denmark between January 1, 2005, and December 31, 2006. A study questionnaire was sent to the women between January and April 2008. MAIN OUTCOME MEASURES: Prevalence, location, and severity of persistent pain and sensory disturbances in 12 well-defined treatment groups assessed an average of 26 months after surgery, and adjusted odds ratio (OR) of reported pain and sensory disturbances with respect to age, surgical technique, chemotherapy, and radiotherapy. RESULTS: By June 2008, 3253 of 3754 eligible women (87%) returned the questionnaire. A total of 1543 patients (47%) reported pain, of whom 201 (13%) had severe pain, 595 (39%) had moderate pain, and 733 (48%) had light pain. Factors associated with chronic pain included young age (18-39 years: OR, 3.62; 95% confidence interval [CI], 2.25-5.82; P < .001) and adjuvant radiotherapy (OR, 1.50; 95% CI, 1.08-2.07; P = .03), but not chemotherapy (OR, 1.01; 95% CI, 0.85-1.21; P = .91). Axillary lymph node dissection (ALND) was associated with increased likelihood of pain (OR, 1.77; 95% CI, 1.43-2.19; P < .001) compared with sentinel lymph node dissection. Risk of sensory disturbances was associated with young age (18-39 years: OR, 5.00; 95% CI, 2.87-8.69; P < .001) and ALND (OR, 4.97; 95% CI, 3.92-6.30; P < .001). Pain complaints from other parts of the body were associated with increased risk of pain in the surgical area (P < .001). A total of 306 patients (20%) with pain had contacted a physician within the prior 3 months for pain complaints in the surgical area. CONCLUSION: Two to 3 years after breast cancer treatment, persistent pain and sensory disturbances remain clinically significant problems among Danish women who received surgery in 2005 and 2006.

BACKGROUND: Few neuroimaging investigations of pain in elderly adults have focused on the hippocampus, a brain structure involved in nociceptive processing that is also subject to involution associated with dementing disorders. The goal of this pilot study was to examine MRI- and magnetic resonance spectroscopy (MRS)-derived hippocampal correlates of pain in older adults. METHODS: A subset of 20 nondemented older adults was drawn from the Einstein Aging Study, a community-based sample from the Bronx, NY. Pain was measured on 3 time scales: 1) acute pain right now (pain severity); 2) pain over the past 4 weeks (Short Form-36 Bodily Pain); 3) chronic pain over the past 3 months (Total Pain Index). Hippocampal data included volume data normalized to midsagittal area and N-acetylaspartate to creatine ratios (NAA/Cr). RESULTS: Smaller hippocampal volume was associated with higher ratings on the Short Form-36 Bodily Pain (r(s) = 0.52, p = 0.02) and a nonsignificant trend was noted for higher ratings of acute pain severity (r(s) = -0.44, p = 0.06). Lower levels of hippocampal NAA/Cr were associated with higher acute pain severity (r(s) = -0.45, p = 0.05). Individuals with chronic pain had a nonsignificant trend for smaller hippocampal volumes (t = 2.00, p = 0.06) and lower levels of hippocampal NAA/Cr (t = 1.71, p = 0.10). CONCLUSIONS: Older adults who report more severe acute or chronic pain have smaller hippocampal volumes and lower levels of hippocampal N-acetylaspartate/creatine, a marker of neuronal integrity. Future studies should consider the role of the hippocampus and other brain structures in the development and experience of pain in healthy elderly and individuals with Alzheimer disease.

Objective: Our goal was to establish the clinical presentation and features of pain attacks in children with recurrent abdominal pain (RAP) and urolithiasis. Methods: We compared the rate of previous appendectomy among 100 consecutive patients with that of 270 control subjects. We also compared the frequency of pain attacks with that reported by children with functional or organic gastrointestinal RAP. Results: Fifty-three patients had no history of dysuria or gross hematuria, and only 35 had hematuria at the first visit; 41 patients were evaluated for urolithiasis only because of a family history of kidney stones associated with RAP. Twenty-nine patients had been previously hospitalized for abdominal symptoms. Sixteen patients and 4 control subjects (1.5%) had undergone a previous appendectomy (P < .0001). Two to 28 months before the diagnosis of urolithiasis, 37 patients underwent abdominal ultrasonography, which did not show urinary stones. Sixty-nine percent of subjects younger than 8 years of age had central/diffuse abdominal pain. The mean frequency of pain attacks was 4 to 9 times lower than in patients with functional or organic gastrointestinal RAP. Conclusions: Because of the inconstant occurrence of dysuria and hematuria, the location of pain in areas other than the flank, and the lack of calculi shown on imaging studies performed after pain attacks, the urologic origin of pain may be overlooked and ineffective procedures performed. The possibility of urolithiasis should be considered in children with RAP who have a family history of urolithiasis and/or infrequent pain attacks, even when dysuria and hematuria are lacking, and in younger children even when pain is not lateral.

BACKGROUND: The WHO's three-step guideline for cancer pain management has been introduced in China; however, there remain large differences in the standards of cancer pain management between China and other developed countries. This survey was carried out to determine the degree of physician knowledge on morphine use and the factors that impede morphine use in clinical practice in China. METHODS: A self-reported questionnaire was designed and administered to randomly selected physicians in four tertiary hospitals in the cities of Changchun and Changsha in China. Statistical analyses were conducted using SPSS statistical software. RESULTS: Two hundred and one clinical physicians participated in the survey. Physicians who reported having received training in cancer pain management and drug use demonstrated a significantly higher mean score of basic knowledge compared to physicians who reported not having received training (9.31 +/- 2.88:8.23 +/- 2.70, u = 2.74, p < 0.001). The top three cited impediments to widespread clinical use of morphine for cancer pain were: (1) lack of professional knowledge and training; (2) fear of opioid addiction; and (3) physicians' personal preferences to select other drugs. CONCLUSIONS: Medical staffs lack the basic knowledge and harbor misconceptions about the clinical use of morphine for cancer pain treatment. Creating training opportunities for medical staffs is necessary to increase their awareness and knowledge of effective cancer pain management.

Summary Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in morbidly obese patients was evaluated using two doses of local anaesthetic. In this randomised, blinded prospective study, 40 ml of atomised 1% (n = 11) or 2% (n = 10) lidocaine was administered with high oxygen flow as carrier. Outcomes included time for intubation, patient tolerance to airway manipulation, haemodynamic parameters, the bronchoscopist's overall satisfaction, and serial serum lidocaine concentrations. Patients receiving lidocaine 1% had a longer mean (SD) time from the start of topicalisation to tracheal tube cuff inflation than those receiving lidocaine 2% (8.6 (0.9) min vs 6.9 (0.5) min, respectively; p < 0.05). Patients in the 1% cohort demonstrated increased responses to airway manipulation (p < 0.0001), reflecting lower bronchoscopist's satisfaction scores (p < 0.03). Haemodynamic responses to topicalisation and airway manipulation were similar in both groups. Peak plasma concentration was lower in the 1% group (mean (SD) 1.4 (0.3) and 3.8 (0.5) mug.ml(-1), respectively; p < 0.001). Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in the morbidly obese is efficacious, rapid and safe. Compared with lidocaine 1%, the 2% dose provides superior intubating conditions.

Aortic aneurysms are frequent in the elderly who often suffer from relevant co-morbidities. In Germany it is estimated that approximately 250,000 patients suffer from an aortic aneurysm. Due to the high risk of cardiac or pulmonary complications operative management poses a challenge to the anesthesiologist. Especially hemodynamic management during aortic cross-clamping requires anesthesiologic know-how and an anticipatory use of vasodilators and catecholamines. Furthermore, the anesthesiologist has to protect renal function. In order to avoid paraplegia due to spinal ischemia cerebrospinal fluid drainage may be necessary in patients with aneurysms of the thoracic aorta. In recent years endovascular repair of aortic aneurysms has been established in addition to conventional open surgery. As a consequence in some patients aortic surgery can be performed under regional or local anesthesia. In special cases thoracic endovascular repair requires a medicinal induction of heart arrest or the reduction of aortic blood flow by overpacing.

In February 2009 a major case of scientific misconduct was discovered. The American pain researcher Dr. S. Reuben had published 21 papers over a period of 15 years that were found to be fraudulent. Suddenly many advances in postoperative pain therapy which had been assumed to be correct seemed questionable. In this review article the lessons which can be learnt from this case are described. This review also reveals that it is almost impossible for reviewers or readers of scientific journals to detect scientific fraud. However, several warning signs can be identified that might be useful when reading clinical papers. In retrospect many of these signs were detectable in Reuben's studies. Based on the fraudulent papers of Reuben it will be shown how and to what extent falsified results can affect other types of literature, such as practice guidelines, meta-analyses, review articles and oral presentations.

Intraosseous (IO) access is used most frequently for emergency care of critically ill infants and children when IV access cannot be rapidly achieved. Despite its efficacy in such situations, applications outside of the emergency room or resuscitation scenario have been limited. Furthermore, although the technique is emphasized in the teaching of those caring for critically ill infants and children in the emergency room or critical care setting, there is limited emphasis on its potential use in the perioperative setting. When peripheral venous access cannot be achieved in the operating room, alternative means of securing vascular access such as central line placement or surgical cutdown are generally successful; however, these techniques may be time consuming. Anyone providing anesthesia care for infants and children may want to become facile with the use of IO infusions for selected indications. We present the history of IO infusions, review the anatomy of the bone marrow space, discuss the potential role of IO infusions in the perioperative period, and analyze its adverse effect profile.

Objectives To determine the incidence of ECG abnormalities in a healthy adults undergoing a surgical extraction of third molar teeth pre-and post-operatively and to study the effect of local anaesthetics, surgical stress and analgesics on cardiac rhythm.Method One hundred and ninety-eight healthy adult patients taking part in a clinical trial of analgesics were randomly selected for this study. All patients required the removal of at least one impacted mandibular wisdom tooth under local anaesthetic. An ECG was taken at a screening visit and repeated post-operatively 30 minutes after analgesia was given. The effects of analgesia were also monitored to ascertain whether any changes were related to pain experience or the analgesic itself.Results ECG abnormalities were detected in 44 patients at the screening visit. Of these patients, 20 showed rsR complex patterns, seven showed non-specific ST elevation, six patients had an abnormal P wave axis, three patients presented with single atrial premature beats and three patients showed a short PR interval. Other minor abnormalities were occasionally seen. The results recorded were of minimal clinical significance and the numbers are in line with previous research. Post-operative abnormalities were seen in 60 patients. Nineteen patients showed rsR complex patterns, sinus arrhythmias were seen in 11 individuals, seven patients showed non-specific ST elevation and six patients had an abnormal P-wave axis. Other minor abnormalities were occasionally seen.Conclusion Although the results were not statistically significant, some of the patients did show clinically relevant abnormalities which necessitated referral to a cardiologist. These included: marked ST elevation; marked ST depression and one case of Right Bundle Branch Block (RBBB).