M.F. Stevens

Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients.

Abstract.Objective:Inflammatory cytokines as well as nitric oxide (NO) play a key role in the pathogenesis of persistent and exaggerated pain states. To document this, we investigated whether a range of cytokines and NO were detectable in the plasma of chronic pain patients and whether cytokine and NO levels correlated with pain severity.Methods:Plasma samples of 94 chronic pain patients and 6 healthy volunteers were obtained. Average pain intensity during the last 24h was assessed on a 11-point numeric rating scale and patients were distributed to three groups: light, moderate and severe pain. The concentrations of TNF-α, GM-CSF, interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, IL-2, IL-4, IL-5, IL-10 and nitrate/nitrite were determined.Results:Patients with light pain demonstrated significantly increased levels of IL-6 compared to controls. In the severe pain group IL-6 and nitrate/nitrite were significantly increased. Serum concentrations of IL-1β, TNF-α, IL-2 and IL-4 were increased but as we adjusted the level of significance at p = 0.0045, most cytokine plasma levels failed to reach statistical significance.Conclusions:Pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IFN-γ, TNF-α) in the plasma correlate with increasing pain intensity. Chronic pain patients show a significant increase in plasma levels of NO in comparison to healthy controls.

Screening of neuropathic pain components in patients with chronic back pain associated with nerve root compression: a prospective observational pilot study (MIPORT)

ABSTRACT Objective: Chronic back pain is characterized by a combination of neuropathic and nociceptive mechanisms of pain generation. The prevalence of the neuropathic pain component is unknown. Thus, in the context of an explorative study, we aimed to determine the prevalence of signs and symptoms indicating neuropathic pain in adult patients treated by orthopaedists. We also aimed to assess the usefulness of handheld computers (PDAs) in data collection. Methods: Prospective epidemiological study in 18 orthopaedic practices or centres throughout Germany. Physician and patient questionnaires (paper/pencil or on handheld computers, PDAs) for patients with back pain of at least 3 months in duration were applied, as well as the von Korff score to assess pain intensity (visual analogue scale, VAS; 0 = no pain, 10 = worst possible pain) and pain characteristics, the Hannover Functional Ability Questionnaire (FFbH-R), and if patients agreed to provide information, the short-form Patient Health Questionnaire (PHQ-D) for depression. Results: For 717 patients, both patient and physician questionnaires were available. Mean patient age was 56 years; pain was predominantly located in the low back (87%). Median current pain intensity on the VAS was 5.0. Confirmed key signs and symptoms indicated neuropathic pain was frequent, e.g. radicular pain radiating beyond the knee towards the foot (40.0%), positive Lasegue sign (18.4%), or absent patellar reflex (17.3%). A third of all patients (33.5%) had ≥ 3 characteristic signs for neuropathic pain. Patient functionality was severely reduced (median 43.3%). There were no relevant differences in outcomes between patients using the paper/pencil method (47%) versus those preferring PDAs (53%). Conclusion: Screening for neuropathic pain in this setting is feasible with simple questionnaires and scales on PDAs. Neuropathic pain is a major contributor to chronic back pain and a frequent component in patients seen by orthopaedists. At least one third of all patients should undergo additional diagnostic measures to confirm the cause of neuropathic pain.

The effect of mirtazapine in patients with chronic pain and concomitant depression

ABSTRACT Objective: To evaluate the safety, tolerability and efficacy of mirtazapine in patients with the primary diagnosis of chronic pain and concomitant depression in an open post-marketing surveillance study. Research design and methods: 594 patients with a primary diagnosis of at least one chronic pain syndrome (minimum duration of 3 months) and the diagnosis of concomitant depression, appropriately made by a neurologist or psychiatrist, were recruited at psychiatric and/or neurological outpatient facilities throughout Germany. The primary efficacy parameter was pain at baseline and endpoint using a patient self-assessment scale. Secondary analyses were performed at baseline, week 1 (day 7 ± 2), week 4 (day 28 ± 4) and at endpoint (day 42 ± 4 or early termination) and included safety and tolerability assessments. Investigators rated the severity of different potential co-morbidities (including depression) with a four-step rating scale (not present, mild, moderate, severe). Results: 594 patients were enrolled and treated with mirtazapine (mean daily dose of 34.5 ± 10.4u2009mg at study endpoint). A statistically significant (u2009p < 0.0001; one sample sign test) reduction of pain from baseline to endpoint was found for the overall population. The percentage of patients free of pain or with only moderate pain increased significantly, irrespective of patients’ age or pain syndromes. Furthermore, we found a substantial improvement from baseline to endpoint regarding co-morbidities such as sleep disturbance, irritability and exhaustion. The number of adverse events was low (< 7%; n = 37), with fatigue (n = 13) and weight gain (n = 11) occurring most frequently. No previously-unknown side effects occurred. One hundred and six patients (18%) discontinued mirtazapine during the study. The main reason was lack of efficacy (6%, n = 33), which may be a reflection of sub-optimal response to the anti-depressant or analgesic effect of the drug, but no appropriate rating scale was used to clarify this question. Only a small number of patients stopped the drug due to adverse events (3%; n = 15). At study endpoint, the majority of physicians and patients rated the overall efficacy and tolerability of mirtazapine as good or very good. Most patients (80%) continued the therapy after 6 weeks. Conclusions: Despite the limitations of an open observational study, our findings suggest that mirtazapine is a safe and well-tolerated drug for use in daily clinical practice. It still remains unclear whether the reduction of pain, the enhancement of the depressed mood or the combination of both effects led to these results. Nevertheless, our data point to a potential beneficial effect of mirtazapine in the treatment of patients with pain and concomitant depression. However, more systematic research, including placebo-controlled studies, and further empirical testing are necessary.

Uniform distribution of skin-temperature increase after different regional-anesthesia techniques of the lower extremity.

Background and Objectives: Skin-temperature increase is a reliable but late indicator of success during regional-anesthesia techniques. The goal of this study is to determine the distribution of skin-temperature changes during different regional techniques. Does skin temperature increase in the whole area innervated by the blocked neural structures or only in certain regions within this area with the capability to react preferentially to sympathetic block (i.e., vessel-rich skin)? Although onset time may vary between different regional-anesthetic techniques, we hypothesized that the distribution of skin warming is equal. Methods: Skin temperature was assessed continuously by infrared thermography in 24 patients who received either combined femoral-nerve and sciatic-nerve block, epidural anesthesia, or spinal anesthesia. Results: Apart from differences in time of onset, no differential spatial distribution of skin-temperature changes could be detected. The earliest and greatest rise of skin temperature occurred at the great toe (10.6°C ± 0.4°C), became smaller proximally, and was negligible above the ankles, irrespective of the type and extent of block. Videothermography revealed that cold blood flows through subcutaneous veins immediately after onset of sympathetic block and initially decreases skin temperature (0.6°C ± 0.3°C) during onset of spinal anesthesia. Conclusion: Irrespective of the applied regional-anesthetic technique, skin-temperature changes are more pronounced distally. Thermography prevents false measurements of skin temperature above subcutaneous veins and displays flow of cold blood as the mechanism of initial skin-temperature drop after regional anesthesia. Measurements of skin-temperature increase cannot be used to evaluate the extent of analgesia or sympathetic block.

A single intravenous dose of prednisolone induces phosphatidylserine externalization, loss of surface marker expression and a 24-h net increase in human peripheral blood lymphocytes ex vivo

To understand how corticosteroids act; a characterization of their effects on lymphocytes is necessary. The effect of in vivo corticosteroids on lymphocyte subpopulations, their surface molecules and externalization of phosphatidylserine (apoptosis) is examined. In a crossover study, a single, intravenous dose of 2xa0mg/kg prednisolone or saline was given to six male adult human volunteers. Blood samples were withdrawn before and 30xa0min, 2, 5, 23 and 29xa0h thereafter. Lymphocyte subsets were determined by FACS analysis. Externalization of phosphatidylserine was measured by Annexin-V; cell fragments were excluded by propidium iodide staining. Lymphocyte number decreased from 2,007xa0±xa0473 to 634xa0±xa0119xa0μl after 5xa0h and rose to 3,112xa0±xa0436xa0μl after 23xa0h. CD4, CD8 and B cell counts declined significantly after 5xa0h (Pxa0≤xa00.01). The expression of CD28 or CD95 on T cells and the natural killer cells were unaffected. There was a significant rebound of lymphocyte numbers above baseline 23xa0h after prednisolone. At baseline 9.9xa0±xa03.8% of cells in the lymphocyte gate did not stain for CD3, CD20 or CD56 (referred to as “null cells”). 5xa0h after application of prednisolone, there was a significant increase of “null cells” (28xa0±xa012%, Pxa0=xa00.018). The percentage of phosphatidylserine positive CD4 cells rose from 8.1xa0±xa03.3 to 19.8xa0±xa08% after intravenous prednisolone, while the percentage of phosphatidylserine positive CD8, B and NK cells remained largely unchanged. Prednisolone induces a most significant depletion of CD4 cells, which to some degree is associated with apoptosis. The net increase of lymphocyte numbers 23xa0h after prednisolone application may be a beneficial late effect of a single i.v. prednisolone shot.

Increase in skin temperature after spinal anesthesia in infants

Background and Objectives: The relatively stable hemodynamics during spinal anesthesia in infants have been attributed to a less active sympathetic nervous system in comparison with adults. Thus, the authors evaluated sympathetic block primarily by measurement of skin temperature and secondarily by determination of noninvasive blood pressure as an indirect sign of sympatholysis. Methods: In 15 infants (postconceptual age: 45.0 ± 4.8 weeks; weight: 4.0 ± 1.2 kg) scheduled for repair of inguinal hernia under spinal anesthesia, skin temperature at the T4 level and at the plantar foot was measured before and after spinal anesthesia. Spinal anesthesia was induced at the L4/L5 interspace with 0.5% hyperbaric bupivacaine 1 mg/kg with 10 μg/kg adrenaline added. Results: Temperature at the plantar foot after spinal anesthesia rose significantly from 33.0°C ± 1.3°C to 34.7°C ± 1.4°C within 10 minutes and to 35.6°C ± 0.9°C after 20 minutes (P < .0001), whereas the temperature at the thorax remained constant at 35°C to 36°C. Systolic and diastolic blood pressure decreased by 15.9 ± 11.4 mm Hg and 9.0 ± 9.2 mm Hg, respectively (P < .01), but remained within normal range in all cases. Conclusions: The authors found a significant increase in skin temperature of the feet within 10 minutes as a sign of sympatholysis, whereas trunk temperature remained constant. Blood pressure decreased but remained within the normal range, despite the observed sympatholysis.

Inactivation of baroafferents leads to loss of barosensitivity without changes in nerve morphology

Baroreceptors are stretch-sensitive mechanoreceptors, which are silenced by preventing distension of the receptor zone. Does chronic inactivation of these peripheral afferents alter their function or morphology? Compound action potentials and morphometry of carotid sinus nerves of 10 rabbits were investigated. The baroafferents were inactivated by embedding the pressure-released carotid sinus into silicon gel. The success of this procedure was validated by the absence of spike activity of the sinus nerve during normal and elevated systemic blood pressure. The contralateral vessels of the same animals were sham-operated and also embedded into silicon, but without prevention of wall movements. After 5, 7, 14 or 28 days the nerves were functionally reinvestigated before and after release of the sinus wall. Afterwards, the morphology of the nerve cross-sections was analysed by morphometry of electron micrographs. Baroafferents did not regain spike activity during immobilisation of the sinus wall. After release of the carotid sinus wall only nerves inactivated for five days regained their pulse synchronous baroreceptor discharge. Following seven days of inactivation, baroreceptor discharge could be elicited by maximal pressure elevation in only one of three nerves. At any time later, the baroreceptor response to arterial pressure changes was lost completely. The activity of the control nerves was preserved after 28 days. No obvious differences in fibre size and myelin thickness were observed between inactivated and control nerves. Inactivation of baroafferents for more than one week leads to a loss of pressure-dependent spike activity. Since morphology did not differ between inactivated and control nerves, it is suggested that changes of baroreceptor endings are responsible for this loss of function.

Incidental recognition of an aspirated tablet in an oesophagectomized patient

case highlights the overall complexity of the management of paraplegia after epidural anaesthesia in a patient unable to undergo MRI scanning. Appendix 4 of the NAP3 report gives an example of an algorithm to manage patients who have weak legs after neuraxial blocks. In addition, it is desirable that the diagnostic pathway is equally predefined, so that patients who are unable to undergo MRI scanning can be diagnosed without delay. Detection and management of epidural haematomas related to anaesthesia in the UK: a national survey of current practice. Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable-cardioverter defibrillators at 1.5 tesla. Editor—We report an incidental recognition of silent aspiration of a tablet given before operation during routine fibreoptic inspection of the double-lumen tube position in a patient with a previous oesophagectomy. A 64-yr-old woman presented with a carcinoma of the middle oesophagus. An abdomino-thoracic oesophagect-omy was combined with the gastric pull-up technique. Two months after the primary intervention, the patient required surgical treatment of a persistent chylothorax. On the day of operation, the patient received her oral medication (including diclofenac 50 mg) without any sedatives. No opioids had been given in the previous 48 h. A rapid-sequence induction was performed and the trachea was intubated with a 37 F left-sided double-lumen tube. The correct positioning of the tube was verified by broncho-scopy and incidentally, a tablet was recognized in the right main bronchus. The tablet was too large to be extracted through the double-lumen tube. Therefore, the tube was replaced by a single-lumen tube (inner diameter 7.0 mm), the tablet was aspirated to the tip of the bronchoscope with the suctioning channel and transferred into the tube. Then, the tube together with the tablet and the broncho-scope were carefully removed. Subsequently, the double-lumen tube was reinserted, the whole bronchial tree was re-inspected and the operation started as scheduled. Laboratory analysis of the tablet revealed that the main component was diclofenac. This result fitted to size and colour of the extracted tablet. Aspiration of gastric content is a common problem after oesophagectomy and responsible for the high incidence of pulmonary complications in these patients. This case demonstrates that asymptomatic aspiration of a solid tablet can occur even nearly 2 months after oesophagectomy. Another important aspect of this case is the difficulty to remove a moist tablet without disintegration within …