David Champion

Purpose: Our aims were to investigate in adults, as we have shown in three paediatric samples, associations between a history of iron deficiency (whenever acquired and treated) and history (> 3 months) of primary, overlapping and multisite chronic pain conditions, and to investigate associations between history of iron deficiency, anxiety, and depression. Participants and Methods: We recruited adult twins and their families from the Australian Twin Registry database. Responders addressed questionnaires about lifetime history of iron deficiency > 3 months, diagnosed and treated by a physician, and a history > 3 months of listed pain conditions, anxiety and depression. The emphasis was on life history, not current status, of each of these conditions and such questions were the only practical method. Logistic regression, using generalized estimating equation to account for correlations within twin families, was employed to assess relationships between iron deficiency and pain conditions and the psychological conditions. Results: Of the 1519 adult responders, 1326 addressed the criteria for iron deficiency, and the prevalence was 38.7% in females and 2.4% in males. Iron deficiency as statistical predictor was significantly associated with migraine (Odds ratio (OR)=1.70, p=0.001), headache (OR=1.37, p=0.03), recurrent abdominal pain (OR=1.97, p< 0.001), dysmenorrhea (OR=2.18, p< 0.001), anxiety (OR=1.88, p< 0.001) and depression (OR=2.06, p< 0.001). Iron deficiency, anxiety and depression, as statistical predictors, were univariately and multivariately associated with the number of pain conditions (all p< 0.05). Conclusion: A history of iron deficiency in a community sample of adults was associated with most individual, primary, overlapping and multisite pain conditions tested, and multivariately associated with the number of pain conditions, and with anxiety and depression. We hypothesize, consistent with these results, that previous or current iron deficiency, even when treated, influences pain sensitivity and multiplicity directly and through known effects on anxiety and depression.

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.

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.

The primary pain disorders of childhood are highly prevalent but have infrequently been studied collectively. Genetic influences have been suggested to be causally implicated. Surveys were sent to 3909 Australian twin families, assessing the lifetime prevalence of growing pains, migraine, headache, recurrent abdominal pain, low back pain, and persistent pain (not otherwise specified) in pediatric twins and their immediate family members. Comparisons between monozygous (MZ) and dizygous (DZ) twin pair correlations, concordances and odds ratios were performed to assess the contribution of additive genetic influences. Random-effects logistic regression modelling was used to evaluate relationships between twin individuals and their co-twins, mothers, fathers and oldest siblings with the subject conditions. Twin analyses of responses from 1016 families revealed significant influence of additive genetic effects on the presence of growing pains, migraine, and recurrent abdominal pain. The analyses for headache, low back pain, and persistent pain overall did not conclusively demonstrate that genetic influences were implicated more than shared environmental factors. Regression analyses demonstrated varying levels of significance in relationships between family members and twin individuals for the tested conditions, with strongest support for genetic influences in growing pains and migraine. These data, together with previously published association analyses, suggest common causal influences including genes.

We aimed to evaluate the utility of clinical somatosensory testing (SST), an office adaptation of laboratory quantitative sensory testing, in a biopsychosocial assessment of a pediatric chronic somatic pain sample (N = 98, 65 females, 7–18 years). Stimulus–response tests were applied at pain regions and intra-subject control sites to cutaneous stimuli (simple and dynamic touch, punctate pressure and cool) and deep pressure stimuli (using a handheld pressure algometer, and, in a subset, manually inflated cuff). Validated psychological, pain-related and functional measures were administered. Cutaneous allodynia, usually regional, was elicited by at least one stimulus in 81% of cases, most frequently by punctate pressure. Central sensitization, using a composite measure of deep pressure pain threshold and temporal summation of pain, was implied in the majority (59.2%) and associated with worse sleep impairment and psychological functioning. In regression analyses, depressive symptoms were the only significant predictor of pain intensity. Functional interference was statistically predicted by deep pressure pain threshold and depressive symptoms. Manually inflated cuff algometry had comparable sensitivity to handheld pressure algometry for deep pressure pain threshold but not temporal summation of pain. SST complemented standard biopsychosocial assessment of pediatric chronic pain; use of SST may facilitate the understanding of disordered neurobiology.