Back Pain without Disease or Substantial Injury in Children and Adolescents: A Twin Family Study Investigating Genetic Influence and Associations.

This twin family study first aimed to investigate the evidence for genetic factors predicting the risk of lifetime prevalence of non-specific low back pain of at least three months duration (LBP (life)) and one-month current prevalence of thoracolumbar back pain (TLBP (current)) using a study of children, adolescents, and their first-degree relatives. Secondly, the study aimed to identify associations between pain in the back with pain in other regions and also with other conditions of interest. Randomly selected families (n = 2479) with child or adolescent twin pairs and their biological parents and first siblings were approached by Twins Research Australia. There were 651 complete twin pairs aged 6-20 years (response 26%). Casewise concordance, correlation, and odds ratios were compared for monozygous (MZ) and dizygous (DZ) pairs to enable inference about the potential existence of genetic vulnerability. Multivariable random effects logistic regression was used to estimate associations between LBP (life) or TLBP (current) as an outcome with the potentially relevant condition as predictors. The MZ pairs were more similar than the DZ pairs for each of the back pain conditions (all p values < 0.02). Both back pain conditions were associated with pain in multiple sites and with primary pain and other conditions using the combined twin and sibling sample (n = 1382). Data were consistent with the existence of genetic influences on the pain measures under the equal environments assumption of the classic twin model and associations with both categories of back pain were consistent with primary pain conditions and syndromes of childhood and adolescence which has research and clinical implications.

Biopsychosocial sequelae of chronically painful injuries sustained in motor vehicle accidents contributing to non-recovery: A retrospective cohort study.

BACKGROUND: Claimants with chronically painful injuries sustained in motor vehicle accidents (MVAs) undergo assessment and management influenced by insurance and medico-legal processes defined by a biomedical paradigm which is discordant with best evidence. We aim to demonstrate the impact of biopsychosocial factors on post-MVA sequelae which contribute to non-recovery. METHODS: This was a retrospective cohort study of medico-legal documents and reports on 300 consecutive claimants referred to a pain medicine physician over 7 years (2012-2018) for assessment of painful musculoskeletal injuries post-MVA. One hundred data items were extracted from the medico-legal documents and reports for each claimant and entered into an electronic database. Post-MVA sequelae were analysed using chi-square analysis (OR >2) for significant associations with demographic, pre-MVA and post-MVA variables. Factors with significant associations were entered into a logistic regression model to determine significant statistical predictors of post-MVA sequelae contributing to non-recovery. RESULTS: The claimants were aged 17 to 80 years (mean age 42 years), and approximately half (53%, n=159) were female. The time from MVA to interview averaged 2.5 years. Widespread pain was present in 18% (n=54), and widespread somatosensory signs implying central sensitisation (OR=9.85, p<.001) was the most significant multivariate association. Long-term opiate use post-MVA (32%) was predicted by pre-MVA sleep disturbance (OR=5.08, p=.001), post-MVA major depressive disorder (MDD) (OR=3.02, p=.003) and long-term unemployment (OR=2.22. p=.007). Approximately half (47%, n=142) required post-MVA support from a psychologist or psychiatrist. Post-traumatic stress disorder (PTSD) was diagnosed by a psychiatrist or psychologist in 20% (n=59), yet early identification of risk of PTSD was rare. Pre-MVA, 89.4% (n=268) were studying or employed. Permanent unemployability post-MVA occurred in 35% (n=104) and was predicted by MDD (OR=3.59, p=.001) and antidepressant use (OR=2.17, p=.005). Major social change post-MVA (70%) was predicted by older age (OR=.966, p=.003), depressive symptoms (OR=3.71, p<.001) and opiate use (OR=2.00, p=.039). CONCLUSIONS: Biomedical factors, including older age, impaired sleep and indicators of widespread central sensitisation, and psychological factors, including stress, anxiety and depression, were the most prominent multivariate associations as statistical predictors of major adverse sequelae contributing to non-recovery for claimants with chronic pain post-MVA.

Primary dysmenorrhoea in adolescents and young women: A twin family study of maternal transmission, genetic influence and associations.

AIMS: The extent to which maternal transmission of primary dysmenorrhoea is genetically determined in adolescents and young women has yet to be determined. We aimed to assess heritability and associations relevant to primary pain syndromes using a twin family study. METHODS: Participants were young menstruating female twins, and their oldest sisters and mothers, whose families were registered with Twins Research Australia and previously participated in a twin family study of primary paediatric pain disorders. Questionnaire packs were mailed, assessing current maximum and average menstrual pain intensity, current pain interference with activities and retrospective dysmenorrhea secondary symptoms. RESULTS: The sample comprised 206 twin individuals (57 monozygous (MZ) and 46 dizygous (DZ) pairs) aged 10-22 years, eldest siblings (n = 38) aged 13-28 years and mothers (n = 101) aged 32-61 years. The estimated regression coefficient of the relationship between mother-daughter and twin-sibling dyads indicated significant associations for the measures of dysmenorrhea and supported heritability. Adjusted for age, the within twin-pair correlation for MZ twins was generally more than twice that of DZ twins. Heritability estimates were maximal pain intensity 0.67 (P = 3.8 × 10-11 ), average pain intensity 0.63 (P = 3.7 × 10-10 ), pain interference 0.57 (P = 1.8 × 10-8 ) and retrospective symptoms 0.57 (P = 1.8 × 10-8 ). Twin individuals with a lifetime (three-month) history of iron deficiency and those with painless restless legs syndrome (RLS) were significantly more likely to have more intense pain associated with menstruation. CONCLUSION: Primary dysmenorrhea in adolescents and young women was shown to be relatively strongly genetically influenced and associated especially with a history of iron deficiency and painless RLS which have potential therapeutic implications.

Improved definition of growing pains: A common familial primary pain disorder of early childhood.

Background: Commonly applied diagnostic criteria for growing pains (GP) have evolved without determination by an authoritative representative body. GP and restless legs syndrome (RLS) share anatomical, distributional, temporal, and other clinical features and are associated in individuals over time, in families, and in population samples. In this study, we tested the hypothesis that GP, diagnosed by widely used criteria, is confounded by cases of painful restless legs syndrome (RLS-Painful). Methods: A twin family study of genetic influence and associations of GP using questionnaires was administered by Twins Research Australia. Twins (3-18 years; monozygous 503, dizygous 513), their oldest siblings, mothers, and fathers were randomly selected from the twin registry. Family members completed the questionnaires assessing lifetime prevalence of GP by commonly applied criteria and covariates including the history of iron deficiency and pediatric pain disorders. A GP-Specific phenotype was defined as GP without urge to move the legs. We determined similarities in twin pairs for the GP and GP-Specific phenotypes, family associations, and estimated familial and individual-specific associations for each phenotype. Results: Lifetime prevalence was one-third lower for GP-Specific than for GP among the twin and family members. Monozygous twin pairs were more similar than dizygous twin pairs for GP and for the derived GP-Specific phenotype by three methods, consistent with genetic influence. There were familial associations, but the essential evidence for genetic influence was the twin-cotwin data. GP was associated, in multivariable analyses, with migraine, headaches, recurrent abdominal pain, and iron deficiency, while GP-Specific associations were limited to migraine and headaches. Conclusions: GP is hybrid, one-third of cases having symptoms and associations of RLS, necessarily RLS-Painful. GP-Specific (without symptoms and associations of RLS) could have a genetic etiology. We propose new criteria to facilitate etiological and therapeutic research.

Electrical injury: Chronic pain, somatosensory dysfunction, post traumatic stress and movement disorders.

INTRODUCTION AND AIMS: We aimed in this case series to identify shortcomings in assessment of long-term painful and psychosocial consequences of EI and to demonstrate the value of biopsychosocial assessment and the commonalities in outcomes. METHODS: We retrospectively analyzed 15 cases from 2004 to 2019 of adult claimants assessed in a medico-legal practice for complex chronic pain disorders secondary to EI. Extensive biopsychosocial information, including 165 data items on pre- and post-injury observations, were collected on each. Cutaneous and deep pressure somatosensory examination was performed and questionnaires for psychological evaluation and restless legs syndrome completed. A comprehensive literature review and descriptive analysis was conducted. RESULTS: Pre-injury, most claimants worked (12/15), did not receive government benefits (14/15) and had no primary pain disorder (9/15). EIs were severe (14/15), where chronic post-traumatic pain, typically high impact with nociplastic features, was regional in 5 and widespread in 10. Somatosensory signs in wide distribution in all cases implied central sensitization. Movement disorders included digital dyskinesia (5/15), involuntary muscle contractions (7/15) and restless legs syndrome in 7. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) post-traumatic stress disorder (PTSD) criteria were met in 12/15, and 14/15 experienced depression and impaired sleep. Severe social impacts, notably including loss of employment resulting in financial stresses, were common. CONCLUSIONS: Biological, psychological and social consequences of EI revealed extensive similarities. Disability was generally severe, moreso than indicated in clinical records, influenced by relative paucity of primary pathology, inadequate pain-orientated somatosensory testing and insufficient application of biopsychosocial assessment and management.

Trajectory of Pain, Functional Limitation, and Parental Coping Resources Following Pediatric Short-stay Surgery: Factors Impacting Rate of Recovery.

OBJECTIVES: Although there are many benefits of short-stay hospital admissions for high volume, pediatric surgical procedures, this model of care places greater responsibility on parents for the management of children's pain. This study aimed to document the trajectory of child pain outcomes and a range of parent-reported functional outcomes following discharge from a short-stay surgical admission. Moreover, we aimed to document the trajectory of parental perceived personal coping resources. Second, we assessed whether parental dispositional factors, assessed before hospital discharge, predicted the child's pain intensity and parent-reported functional recovery. METHODS: Participants included children (aged 4 to 14 y) admitted for a short-stay tonsillectomy or appendectomy, and their parents. Parents completed a questionnaire before discharge from hospital. Demographic and surgical information was recorded from medical records. Following discharge, daily assessments of pain and functioning were carried out over a 10-day period using iPods or mobile phones. Predischarge and postdischarge data were obtained for 55 child and parent dyads. RESULTS: Pain intensity scores returned to low levels (2/10 or less) by day 5 for appendectomy and day 10 for tonsillectomy. Parents' perceived personal coping resources increased more slowly following tonsillectomy than appendectomy. Controlling for time since surgery and parental coping resources, parental pain-related catastrophizing was a significant predictor of child pain and functional recovery. DISCUSSION: Short-stay surgery results in parents facing considerable burden in managing their child's pain and functional impairment over a 10-day period. The potential value of screening for parental pain-related catastrophizing before discharge from hospital warrants further consideration and may enable identification of children likely to experience poorer recovery.

Multidimensional Self-report Assessment of Children's Acute Pain in an Inpatient Setting.

OBJECTIVE: This study assessed the feasibility of administering a multidimensional, self-report pain assessment protocol to children in an inpatient, acute pain context, and sought insight into the interrelationships between sensory, affective, and evaluative pain dimensions. METHODS: A total of 132 children (5 to 16 y) experiencing acute pain were recruited from acute pain ward rounds or the short-stay surgical unit. A multidimensional self-report assessment protocol was administered, assessing pain intensity, pain-related affect, bother, perceived unfairness, and pain expectations (for tomorrow and in 1 wk). Duration of protocol administration was assessed and ease of administration was rated. Pain-related behaviors were rated using the Face, Legs, Activity, Cry, and Consolability (FLACC) Scale. RESULTS: The duration of protocol administration was <2.5 minutes, on average, for all age groups. Median ease of protocol administration was 7/10 for 5- to 7-year-olds and 8/10 for older age groups. Pain-related bother was higher for 14- to 16-year-olds, relative to younger age groups, and significantly correlated with perceived unfairness (r=0.59, P<0.01), intensity (r=0.76, P<0.01), and affect (r=0.33, P<0.05). For younger age groups, bother was significantly positively correlated only with pain intensity (rs=0.59 to 0.79, Ps<0.01) and affect (rs=0.4 to 0.71, Ps <0.05). A stepwise multiple regression analysis found multidimensional self-reported information (especially pain intensity and perceived unfairness), accounted for significant additional amount of variance, beyond that explained by age, pain duration, and observed pain behavior. DISCUSSION: Sensory, affective, and evaluative aspects of children's clinical, acute pain experience may be assessed using self-report tools, which provide unique and valuable information about their pain experience.

Ability of 3- to 5-year-old children to use simplified self-report measures of pain intensity.

Little is known about self-report pain intensity scales best suited for young children. We tested the ability of preschool children to use two simplified scales (concrete ordinal and faces). Three- to 5-year-olds (n = 123) were asked to make binary discriminations ('less' vs 'more' pain) between response options using the Simplified Faces Pain Scale and Simplified Concrete Ordinal Scale and to complete a seriation task. Eighty participants were also asked to use the Simplified Concrete Ordinal Scale, with modified verbal anchors, to rate the loudness of tones and to assess practice effects. Binary discrimination accuracy and seriation ability improved with age. When using the Simplified Concrete Ordinal Scale to rate the loudness of tones, even the 3-year-olds performed significantly better than chance, and performance was better in 4- and 5-year-olds. Little evidence supported the ability of 3-year-olds to use either of the simplified tools in the pain context. The 4-year-olds demonstrated greater accuracy in using the Simplified Concrete Ordinal Scale than the Simplified Faces Pain Scale, suggesting that the Simplified Concrete Ordinal Scale may be more appropriate for this age group.

Why Unidimensional Pain Measurement Prevails in the Pediatric Acute Pain Context and What Multidimensional Self-Report Methods Can Offer.

Although pain is widely recognized to be a multidimensional experience and defined as such, unidimensional pain measurement focusing on pain intensity prevails in the pediatric acute pain context. Unidimensional assessments fail to provide a comprehensive picture of a child's pain experience and commonly do little to shape clinical interventions. The current review paper overviews the theoretical and empirical literature supporting the multidimensional nature of pediatric acute pain. Literature reporting concordance data for children's self-reported sensory, affective and evaluative pain scores in the acute pain context has been reviewed and supports the distinct nature of these dimensions. Multidimensional acute pain measurement holds particular promise for identifying predictive markers of chronicity and may provide the basis for tailoring clinical management. The current paper has described key reasons contributing to the widespread use of unidimensional, rather than multidimensional, acute pediatric pain assessment protocols. Implications for clinical practice, education and future research are considered.

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.

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.

Factors associated with infant pain response following an immunization injection.

OBJECTIVES: Specific potential determinants of infant pain response were assessed in the context of a 4- or 6-month immunization injection. The distal influences of gender, gestational and current age, temperament, and early nociceptive stimuli were considered, as well as the proximal influences of parental and nurse coping-promoting statements within the treatment room. STUDY DESIGN: An observational study design was used. Pain responses in 93 infants receiving an immunization injection were videoed and coded using the Neonatal Facial Coding System (NFCS) and duration of crying was recorded. Parent and nurse vocalizations were coded using the Child-Adult Medical Procedure Interaction Scale-Revised. RESULTS: A multiple regression analysis evaluated the influence of the 5 distal and 2 proximal factors on NFCS scores, and found parental coping-promoting statements in the 30 s period before the injection to have the strongest effect on facial pain response (p<0.01). Parents made significantly more coping-promoting statements (p<0.05), and generally talked more (p<0.05), to female infants than male infants. CONCLUSIONS: The findings suggest that parental behavior in the treatment room has a key role in influencing how infants respond to painful procedures.

Efficacy and safety of acetaminophen vs ibuprofen for treating children's pain or fever: a meta-analysis.

OBJECTIVE: To summarize studies testing the efficacy and safety of single-dose acetaminophen and ibuprofen for treating children's pain or fever. DATA SOURCES: Reports were gathered by searching computerized databases (from their inception through May 2002) and registries, relevant journals, and bibliographies of key articles. STUDY SELECTION: Seventeen blinded, randomized controlled trials with children (<18 years) receiving either drug to treat fever or moderate to severe pain. DATA EXTRACTION: Under a fixed-effects model, outcome measures for an initial single dose of ibuprofen vs acetaminophen were the risk ratio for achieving more than 50% of maximum pain relief, effect size for febrile temperature reduction, and risk ratio for minor and major harm. DATA SYNTHESIS: Ibuprofen (4-10 mg/kg) and acetaminophen (7-15 mg/kg) showed comparable efficacy (3 pain relief trials; 186 children). The risk ratio point estimates was 1.14 (95%confidence interval [CI], 0.82-1.58) at 2 hours after receiving the dose, and 1.11 (95% CI, 0.89-1.38) at 4 hours. Ibuprofen (5-10 mg/kg) reduced temperature more than acetaminophen (10-15 mg/kg) at 2, 4, and 6 hours after treatment (respective weighted-effect sizes: 0.19 [95% CI, 0.05-0.33], 0.31 [95% CI, 0.19-0.44], and 0.33 [95% CI, 0.19-0.47]) (9 fever trials; 1078 children). For ibuprofen 10 mg/kg (acetaminophen, 10-15 mg/kg), corresponding effect sizes were 0.34 (95% CI, 0.12-0.56), 0.81 (95% CI, 0.56-1.03), and 0.66 (95% CI, 0.44-0.87). There was no evidence the drugs differed from each other (or placebo) in incidence of minor or major harm (17 safety trials; 1820 children). CONCLUSIONS: In children, single doses of ibuprofen (4-10 mg/kg) and acetaminophen (7-15 mg/kg) have similar efficacy for relieving moderate to severe pain, and similar safety as analgesics or antipyretics. Ibuprofen (5-10 mg/kg) was a more effective antipyretic than acetaminophen (10-15 mg/kg) at 2, 4, and 6 hours posttreatment.

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.

Methotrexate-induced optic neuropathy.

A 53-year-old Caucasian woman with long-standing, well controlled, severe rheumatoid arthritis, treated with methotrexate, salazopyrin, naprosyn, prednisone and plaquenil, presented with progressive visual loss in each eye. She had a past history of non-necrotizing anterior scleritis that was treated with increased doses of prednisone. She developed left then right central scotomas, reduced vision and optic atrophy. Eventually a diagnosis of methotrexate-induced optic atrophy was made.