Pasquale Scaramozzino

Reference Values of Mechanical and Thermal Pain Tests in a Pain-Free Population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain‐free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body‐mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short‐Form 36 (SF‐36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain-free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.

Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment

&NA; During the last decade, a multi‐modal approach has been established in human experimental pain research for assessing pain thresholds and responses to various experimental pain modalities. Studies have concluded that differences in responses to pain stimuli are mainly related to variation between individuals rather than variation in response to different stimulus modalities. In a factor analysis of 272 consecutive volunteers (137 men and 135 women) who underwent tests with different experimental pain modalities, it was determined whether responses to different pain modalities represent distinct individual uncorrelated dimensions of pain perception. Volunteers underwent single painful electrical stimulation, repeated painful electrical stimulation (temporal summation), test for reflex receptive field, pressure pain stimulation, heat pain stimulation, cold pain stimulation, and a cold pressor test (ice water test). Five distinct factors were found representing responses to 5 distinct experimental pain modalities: pressure, heat, cold, electrical stimulation, and reflex‐receptive fields. Each of the factors explained approximately 8% to 35% of the observed variance, and the 5 factors cumulatively explained 94% of the variance. The correlation between the 5 factors was near null (median ρ = 0.00, range −0.03 to 0.05), with 95% confidence intervals for pairwise correlations between 2 factors excluding any relevant correlation. Results were almost similar for analyses stratified according to gender and age. Responses to different experimental pain modalities represent different specific dimensions and should be assessed in combination in future pharmacological and clinical studies to represent the complexity of nociception and pain experience. Responses to different experimental pain modalities represent different specific dimensions, supporting multimodal pain assessment for clinical and research purposes.

A direct search procedure to optimize combinations of epidural bupivacaine, fentanyl, and clonidine for postoperative analgesia.

Background The authors applied an optimization model (direct search) to find the optimal combination of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate for continuous postoperative epidural analgesia. Methods One hundred ninety patients undergoing 48-h thoracic epidural analgesia after major abdominal surgery were studied. Combinations of the variables of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate were investigated to optimize the analgesic effect (monitored by verbal descriptor pain score) under restrictions dictated by the incidence and severity of side effects. Six combinations were empirically chosen and investigated. Then a stepwise optimization model was applied to determine subsequent combinations until no decrease in the pain score after three consecutive steps was obtained. Results Twenty combinations were analyzed. The optimization procedure led to a reduction in the incidence of side effects and in the mean pain scores. The three best combinations of bupivacaine dose (mg/h), fentanyl dose (&mgr;g/h), clonidine dose (&mgr;g/h), and infusion rate (ml/h) were: 9-21-5-7, 8-30-0-9, and 13-25-0-9, respectively. Conclusions Given the variables investigated, the aforementioned combinations may be the optimal ones to provide postoperative analgesia after major abdominal surgery. Using the direct search method, the enormous number of possible combinations of a therapeutic strategy can be reduced to a small number of potentially useful ones. This is accomplished using a scientific rather than an arbitrary procedure.

The nociceptive withdrawal reflex: Normative values of thresholds and reflex receptive fields

Assessments of spinal nociceptive withdrawal reflexes can be used in human research both to evaluate the effect of analgesics and explore pain mechanisms related to sensitization. Before the reflex can be used as a clinical tool, normative values need to be determined in large scale studies. The aim of this study was to determine the reference values of spinal nociceptive reflexes and subjective pain thresholds (to single and repeated stimulation), and of the area of the reflex receptive fields (RRF) in 300 pain‐free volunteers. The influences of gender, age, height, weight, body‐mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short‐Form 36 (SF‐36) were analyzed by multiple regressions. The 95% confidence intervals were determined for all the tests as normative values. Age had a statistically and quantitatively significant impact on the subjective pain threshold to single stimuli. The reflex threshold to single stimulus was lower on the dominant compared to the non‐dominant side. Depression had a negative impact on the subjective pain threshold to single stimuli. All the other analyses either did not reveal statistical significance or displayed quantitatively insignificant correlations. In conclusion, normative values of parameters related to the spinal nociceptive reflex were determined. This allows their clinical application for assessing central hyperexcitability in individual patients. The parameters investigated explore different aspects of sensitization processes that are largely independent of demographic characteristics, cognitive and affective factors.

Adding Sodium Bicarbonate to Lidocaine Enhances the Depth of Epidural Blockade

It is controversial whether adding CO2 or sodium bicarbonate to local anesthetics enhances the depth of epidural blockade.Repeated electrical stimulation is a reliable test for assessing epidural analgesia and evokes temporal summation. We used this test to investigate the analgesic effect of lidocaine, with or without CO2 or bicarbonate. Twenty-four patients undergoing epidural blockade with 20 mL lidocaine 2% at L2-3 were randomly divided into three groups: lidocaine hydrochloride, lidocaine CO2, and lidocaine plus 2 mL sodium bicarbonate 8.4%. Pain threshold after repeated electrical stimulation (five impulses at 2 Hz), pinprick, and cold test were performed at S1 and L4. Motor block was assessed. The addition of bicarbonate resulted in higher pain thresholds (P < 0.0001), faster onset of action (P = 0.009), and higher degree of motor block (P = 0.004) compared with lidocaine hydrochloride. We found no significant differences between lidocaine CO2 and hydrochloride. Most of these results were not confirmed by pinprick and cold tests. We conclude that the addition of sodium bicarbonate to lidocaine enhances the depth of epidural blockade, increases inhibition of temporal summation, and hastens the onset of block. Pinprick and cold are inadequate tests for comparing drugs for epidural anesthesia. Implications: We measured pain perception during epidural anesthesia by delivering electrical stimuli to the knee and foot. We found that the addition of sodium bicarbonate to the local anesthetic lidocaine enhances analgesia. We observed no effect of adding carbon dioxide to lidocaine. (Anesth Analg 1998;86:341-7)

Epidural fentanyl, adrenaline and clonidine as adjuvants to local anaesthetics for surgical analgesia: meta‐analyses of analgesia and side‐effects

Background: The risk/benefit ratio of adding fentanyl, adrenaline and clonidine to epidural local anaesthetics for improving intraoperative analgesia is unclear. This meta‐analysis was performed to clarify this issue.

Factors associated with hypotension and bradycardia after epidural blockade

In order to identify patient-, anesthesia-, and surgery-related factors influencing the probability of hypotension and bradycardia after epidural blockade, an observational study was conducted on 1050 nonpregnant patients. Backward stepwise logistic regression was performed on the variables hypotension (systolic blood pressure <90 mm Hg) and bradycardia (heart rate <or=to45 bpm). Hypotension and bradycardia occurred in 158 and 24 patients, respectively. The probability of hypotension increased when epidural fentanyl was administered (odds ratio [OR] = 2.18; 95% confidence interval [CI] = 1.16-4.11), with body weight and spread of epidural analgesia, and decreased when a tourniquet was used (OR = 0.01, CI = 0.01-0.02) and bupivacaine instead of carbonated lidocaine was administered (OR = 0.28, CI = 0.14-0.60). Sensitivity and specificity of the model were 89% and 88%, respectively. The probability of bradycardia was less in women (OR = 0.05, CI = 0.01-0.41) and when a tourniquet was used (OR = 0.04, CI = 0.02-0.09). Sensitivity and specificity were 50% and 97%, respectively. In conclusion, our analysis can contribute to identification of patients at high risk to develop hypotension and bradycardia after epidural blockade. If bupivacaine instead of carbonated lidocaine is used and epidural fentanyl is not administered a decrease in the incidence of hypotension may be anticipated. (Anesth Analg 1996;83:1033-40)

A Multifactorial analysis of the spread of epidural analgesia

The controversies about the factors determining the spread of epidural analgesia are partly due to inappropriate methodology or sample size of previous studies. We performed a multivariate regression analysis on 803 ASA class 1–2 non–atherosclerotic adults, undergoing lumbar epidural anaesthesia according to a predefined standardised procedure. The spread of epidural analgesia is more accurately studied by analysing dose/ segment (R2 = 0.671) instead of spread (R2 = 0.271) as dependent variable. The impact of local anaesthetic (2% lidocaine C02 or 0.5% bupivacaine) and addition of adrenaline is not significant. Spread significantly increases with increasing age, weight, body–mass index, dose of local anaesthetic, addition of fentanyl, higher site of injection, and decreasing body height. The impact of age and dose is higher under the age of 40 and at doses lower than 20 ml. Increasing the total dose increases the dose needed to block one spinal segment. Unknown idiosyncratic factors still determine a certain proportion of the sample variance. The addition of adrenaline to lidocaine and the use of bupivacaine improve the predictability of spread. In conclusion, we found clinically significant correlations between a group of factors and epidural spread. Alternative anaesthetic solutions lead to different degrees of predictability.

Investment irreversibility and finance constraints

This paper analyzes the investment behavior of firms in the presence of irreversibility and of a dividend payout constraint. Estimation of investment equations for a panel of U.K. firms shows that the Q model performs well over regions of the sample space where neither constraint is likely to be binding. The constraints are able to account for the empirical significance of cash flow variables for the remaining firms in the sample. Copyright 1997 by Blackwell Publishing Ltd

The Inflationary Consequences of a Currency Changeover: Evidence from the Michelin Red Guide

This paper examines the inflationary consequences of a currency changeover in a simple model of the catering market. It is shown that the change in cash denomination acts as a coordination device shifting the industry to a high-price equilibrium. Empirical evidence based on data from the Michelin Red Guide strongly supports the predictions of our model against competing explanations. A permanent change in relative prices has taken place in Euroland, with strong redistributional effects in favour of some segments of the catering sector.