G. David Champion

The Faces Pain Scale for the self-assessment of the severity of pain experienced by children: development, initial validation, and preliminary investigation for ratio scale properties.

&NA; Altogether 553 children (195 first graders, mean age 6.8 years, and 358 third graders, mean age 8.7 years) participated in the development of a self‐report measure to assess the intensity of childrens pain. The first step was the derivation, from childrens drawings of facial expressions of pain, of 5 sets of 7 schematic faces depicting changes in severity of expressed pain from no pain to the most pain possible. With the set of faces that achieved the highest agreement in pain ordering, additional studies were conducted to determine whether the set had the properties of a scale. In one study, children rank‐ordered the faces on 2 occasions, separated by 1 week. All 7 faces were correctly ranked by 64% (retest 1 week later, 61%) of grade 1 children and by 86% (retest 89%) of grade 3 children. In a second study, the faces were presented in all possible paired combinations. All 7 faces were correctly placed by 62% (retest 86%) of the younger and by 75% (retest 71%) of the older subjects. A third study asked children to place faces along scale: a procedure allowing a check on the equality of intervals. The fourth study checked on whether pain was acting as an underlying construct for ordering the faces in memory. We asked whether children perceived the set as a scale by asking if memory for an ordered set of faces was more accurate than for a random set. The final study checked, with 6‐year‐old children, the test‐retest reliability of ratings for recalled experiences of pain. Overall, the faces pain scale incorporates conventions used by children, has achieved strong agreement in the rank ordering of pain, has indications that the intervals are close to equal, and is treated by children as a scale. The test‐retest data suggest that it may prove to be a reliable index over time of self‐reported pain.

Stereoselective disposition of ibuprofen enantiomers in synovial fluid

The simultaneous disposition of the enantiomers of ibuprofen in synovial fluid and plasma was studied in eight patients with arthritis. Concentrations of the active S‐enantiomer in synovial fluid exceeded those of the R‐enantiomer at all times in all patients with the ratio of S to R concentrations being 2.1 ± 0.3 (mean ± SE). Synovial fluid concentrations fluctuated much less than in plasma and exceeded plasma concentrations from 5.4 ± 0.3 hours for R‐ibuprofen and 5.5 ± 0.6 hours for S‐ibuprofen. Pharmacokinetic analysis suggested that, although the enantiomers diffuse into synovial fluid primarily in the unbound form, there may be significant diffusion of the enantiomers out of synovial fluid in the protein‐bound form in some patients. Interpatient differences in the disposition of the enantiomers of ibuprofen in synovial fluid were evident and may contribute to the interindividual variability in response to treatment with ibuprofen.

Children’s ratings of the intensity and unpleasantness of post-operative pain using facial expression scales

This study explored whether global unidimensional self‐report pain scales based on facial expression help children separately estimate the sensory and affective magnitude of post‐operative pain. Ninety paediatric elective surgery patients (in two age groups: 5–9 and 10–15 years) used each of four scales to estimate pain intensity and pain affect during the first 2 days after surgery. The four scales were: Faces Pain Scale (FPS), Facial Affective Scale (FAS), and the Coloured Analogue Scale (CAS) (one for intensity and one for unpleasantness). As hypothesised, ratings on the FPS correlated more highly with analogue scale ratings for intensity than for unpleasantness, whereas ratings on the FAS correlated more highly with those on the analogue scale for unpleasantness than for intensity. Factor analysis indicated that although all measures loaded on a single dimension of distress, there was an additional weaker factor corresponding to a unique contribution of the FAS. No systematic age effects were observed. It was concluded that the FPS and the FAS may partly measure different aspects of the postoperative pain experience in children, although shared instrument variance may obscure true estimates of covariation in ratings of intensity and affective magnitude. The clinical relevance of the present results remains to be determined.

Needle pain severity in children: Does the relationship between self-report and observed behaviour vary as a function of age?

Reactions to needle pain were observed in children aged 3 to 17 years undergoing venipuncture. The primary aim was to determine whether agreement between observer ratings and childrens self-report of pain varied as a function of the age of the child. A second aim was to explore which factors predicted whether a child spontaneously chose to watch the needle, and whether looking behaviour was related to pain ratings. Results showed that correlations between behavioural and self-report measures were strongest for the 3- to 7-year-olds and weakest for the 12- to 17-year-olds. While the best predictor of self-report ratings was facial reaction for both the 8- to 11- and 12- to 17-year-olds, vocal and verbal reactions were also significant predictor variables for the 3- to 7-year-olds. The profile of a “non-looker” was a child who was older and had experienced few needles, who expected pain and was anxious about the procedure.

A comparison of the Faces Pain Scale and the Facial Affective Scale for children's estimates of the intensity and unpleasantness of needle pain during blood sampling.

To what degree can facial expression scales help children differentiate between the sensory and emotional aspects of the pain experience? This study examined the relationship between childrens ratings on the Faces Pain Scale (an intensity measure), the Facial Affective Scale (an affective measure), and a paired mechanical visual analogue (MVAS) method for measuring the intensity and unpleasantness of pain. It was predicted that ratings on the Faces Pain Scale should correlate best with the MVAS measure of pain intensity rather than unpleasantness. Likewise, ratings on the Facial Affective Scale should correlate best with the MVAS measure of pain unpleasantness (assumed to reflect an emotional dimension) rather than intensity. Eighty children scheduled for blood sampling were selected in two age groups: 4 to 6, and 7 to 10 years. Children rated needle pain using each pain scale. As hypothesized, ratings on the Faces Pain Scale correlated more highly with the MVAS ratings for intensity (r = 0.77) than for unpleasantness (r = 0.52). A smaller reverse finding was confirmed for the Facial Affective Scale which correlated more highly with the MVAS for unpleasantness (r = 0.64) than for intensity (r = 0.51). Factor analysis indicated that ‘pain dimension’ (intensity vs affect) was a relatively weak factor as compared with shared instrument variance (two MVAS vs two face scales). No systematic age effects were observed. In conclusion, the Faces Pain Scale and the Facial Affective Scale may partly measure different aspects of the pain experience in children, although it remains to be determined to what degree the obtained differences are clinically meaningful.

Evaluation of a Brief Parent Intervention Teaching Coping-Promoting Behavior for the Infant Immunization Context A Randomized Controlled Trial

This study was designed to investigate whether a brief intervention encouraging parental coping-promoting talk within the treatment room would have beneficial effects on infant pain responses to an immunization injection. Infant-parent dyads were recruited from a 6-month immunization clinic and randomized to an intervention group (n = 25) or standard care control group (n = 25). Parents in the intervention group received an information sheet describing adult verbalizations associated with better pain outcomes for infants. The immunization procedure was videotaped. Parents in the intervention condition made significantly more coping-promoting statements than parents in the control condition. Infants in the control condition cried significantly longer than infants in the intervention condition. Coping-promoting and distress-promoting statements did not differ in terms of affective quality. Infants whose parents had rated them as more difficult in temperament cried longer following the injection. Teaching parents to engage in coping-promoting behaviors within the infant treatment room is an effective, low-cost intervention.

The Cellular Metabolism and Effects of Gold Complexes

Leads to the cellular effects of the anti-arthritic gold complexes may come from the determination of their metabolism by target cells and, possibly, cells in the immediate environment of the target cells. Polymorphonuclear leukocytes (PMN) and mononuclear cells (monocytes and lymphocytes) are present in inflamed joints of patients with rheumatoid arthritis and these cells have been widely used in pharmacological studies on the gold complexes. It is suggested that the cellular effects of the gold complexes are mediated by the production of aurocyanide. According to this hypothesis, PMN metabolize small quantities of thiocyanate to cyanide which, in turn, converts gold complexes, such as aurothiomalate, to aurocyanide (dicyanogold(I)) which inhibits the functions of PMN and other cells. There is now considerable evidence for this hypothesis from in vitro studies but there is little in vivo work to back up the hypothesis. One of the few in vivo studies which tested the hypothesis involved the examination of the activity of aurothiomalate in the treatment of polyarthritis in Hooded Wistar rats. Activity of aurothiomalate is only shown in animals which received thiocyanate. Hydrogen cyanide is a constituent of cigarette smoke and the aurocyanide formed by the interaction with gold complexes and inhaled hydrogen cyanide rapidly diffuses into red blood cells. Because of the metabolism of hydrogen cyanide to thiocyanate in the liver, there are higher plasma levels of thiocyanate in smokers than in non-smokers. Smokers may have a greater incidence of side effects than non-smokers but there appears to be little difference in therapeutic response, possibly because there is sufficient thiocyanate in extracellular fluid, even in non-smokers, to support the conversion of gold complexes to aurocyanide. The relationship between the metabolism and effects of the orally active gold complex, auranofin are less clear. Auranofin itself is taken up by cells with the loss of the ligands bound to gold while its inhibitory activity against the oxidative burst of PMN decreases with increasing cell density. For example, the lucigenin-dependent chemiluminescence of 106 PMN/ml is 46 percent of control at 0.5 μM auranofin but only 2.2 percent in 2.105 PMN/ml in the presence of the same concentration of auranofin. A potentially active gold complex is a plasma component which is taken up by red blood cells.

Commentary: Multiple Pains as Functional Pain Syndromes

Pain in various parts of the body is reported by many children and adolescents, especially girls. Kroner-Herwig, Gassmann, van Gessel, and Vath (2011, this issue) report on a large community study of youth aged 10–17 years in which 66% of the female respondents and 41% of the males reported pain in two or more body locations within the last 6 months. Headache, abdominal pain, and back pain were the most frequent of these locations. Kroner-Herwig et al. used multiple regression techniques to identify associations as potential predictors of these pains, finding small contributions of psychosocial variables and large contributions of age, sex, and prior pain. Many interesting questions are raised by the findings of Kroner-Herwig et al., for example: (a) Why do multiple pains often cluster or occur sequentially within individuals as they do? (b) What is the basis of the large sex or gender differences in prevalence of pain? (c) Could multiple pains in adolescence predict later chronic pain and psychological illness? We focus in this commentary on the first of these questions. In addressing this question, we briefly survey adult studies related to various functional pain syndromes, finding that they have many shared features and risk factors. We examine twin studies showing shared genetic influences among functional pain syndromes as well as anxiety and depression. We conclude with a portrayal of functional pain syndromes as largely comprising different manifestations of an underlying propensity or vulnerability to respond to stressors with the experience and report of pain, rather than separate disorders. The main constructs discussed in this commentary are summarized in Figure 1. Why do Multiple Pains often Cluster or Occur Sequentially as they do?

Systematic Review of Self-Report Measures of Pain Intensity in 3- and 4-Year-Old Children: Bridging a Period of Rapid Cognitive Development

Claims are made for the validity of some self-report pain scales for 3- and 4-year-old children, but little is known about their ability to use such tools. This systematic review identified self-report pain intensity measures used with 3- and/or 4- year-old participants (3-4yo) and considered their reliability and validity within this age span. The search protocol identified research articles that included 3-4yo, reported use of any pain scale, and included self-reported pain intensity ratings. A total of 1,590 articles were screened and 617 articles met inclusion criteria. Of the included studies, 98% aggregated self-report data for 3-4yo with data for older children, leading to overestimates of the reliability and validity of self-report in the younger age group. In the 14 studies that provided nonaggregated data for 3-4yo, there was no evidence for 3-year-old and weak evidence for 4-year-old children being able to use published self-report pain intensity tools in a valid or reliable way. Preschool-age children have been reported to do better with fewer than the 6 response options offered on published faces scales. Simplified tools are being developed for young children; however, more research is needed before these are adopted. PERSPECTIVE Some self-report pain scales have been promoted for use with 3- and 4-year-old children, but this is on the basis of studies that aggregated data for younger and older children, resulting in overestimates of reliability and validity for the preschool-age children. Scales with fewer response options show promise, at least for 4-year-old children.

Auranofin inhibits the activation pathways of polymorphonuclear leukocytes at multiple sites

In order to characterize the mechanism by which the anti-rheumatic gold complex auranofin (AF) affects the functions of resting and activated polymorphonuclear leukocytes (PMN) the following studies were performed: (1) The effect of AF on the major processes involved in the respiratory burst of PMN: glucose transport and phosphorylation; hexose monophosphate (HMP) shunt activity in intact cells and in a cell-free system; superoxide production by particulate fractions and intact PMN measured as lucigenin-dependent chemiluminescence. (2) A comparison of the effects of AF added to the PMN before, at the time of, or subsequent to the stimulants [N-formyl-methionyl-leucyl phenylalanine (FMLP), concanavalin A (ConA), calcium ionophore (A23187) and phorbol myristate acetate (PMA)]. (3) The effect of AF on PMN activated by two stimulates (PMA, ConA) added sequentially. AF (0.1-10 microM) caused a dose-dependent inhibition of lucigenin-dependent chemiluminescence regardless of the activator (FMLP, ConA, A23187, PMA) when AF was added before the activator. In contrast, when AF was added to PMN after stimulation, it inhibited only the chemiluminescence of PMN stimulated by PMA. Furthermore, the chemiluminescence was largely unaffected by AF in sequentially activated PMN. The relative sensitivity to AF of the various processes studied indicates that blockade of the activation signal appears to be responsible for inhibition of the respiratory burst of PMN.