Pain Reactivity and Plasma β-Endorphin in Children and Adolescents with Autistic Disorder

International audienceBackground: Reports of reduced pain sensitivity in autism have prompted opioid theories of autism and have practical care ramifications. Our objective was to examine behavioral and physiological pain responses, plasma β-endorphin levels and their relationship in a large group of individuals with autism.Methodology/Principal Findings: The study was conducted on 73 children and adolescents with autism and 115 normal individuals matched for age, sex and pubertal stage. Behavioral pain reactivity of individuals with autism was assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and child psychiatrist during blood drawing), and compared to controls during venepuncture. Plasma β-endorphin concentrations were measured by radioimmunoassay. A high proportion of individuals with autism displayed absent or reduced behavioral pain reactivity at home (68.6%), at day-care (34.2%) and during venepuncture (55.6%). Despite their high rate of absent behavioral pain reactivity during venepuncture (41.3 vs. 8.7% of controls, P<0.0001), individuals with autism displayed a significantly increased heart rate in response to venepuncture (P<0.05). Moreover, this response (Δ heart rate) was significantly greater than for controls (mean±SEM; 6.4±2.5 vs. 1.3±0.8 beats/min, P<0.05). Plasma β-endorphin levels were higher in the autistic group (P<0.001) and were positively associated with autism severity (P<0.001) and heart rate before or after venepuncture (P<0.05), but not with behavioral pain reactivity.Conclusions/Significance: The greater heart rate response to venepuncture and the elevated plasma β-endorphin found in individuals with autism reflect enhanced physiological and biological stress responses that are dissociated from observable emotional and behavioral reactions. The results suggest strongly that prior reports of reduced pain sensitivity in autism are related to a different mode of pain expression rather than to an insensitivity or endogenous analgesia, and do not support opioid theories of autism. Clinical care practice and hypotheses regarding underlying mechanisms need to assume that children with autism are sensitive to pain

Molecular signaling within growth plates of the radius and tibia after periosteal stripping: an experimental study in lambs

Periosteal transection and elevation is a standard treatment for angular limb deformities in foals. It is used to correct axis deviations in the limbs at an early age to assure that the foals grow up with straight limbs to improve their chances to reach their full potential as future athletes. Although clinically proven, its mechanisms of action were never elucidated on a more basic scientific level. In this experimental study the molecular response to periosteal stripping was investigated within the growth plate and adjacent perichondrium. The study was based on the hypothesis that a growth restraining feedback loop related to Indian hedgehog (Ihh), parathyroid hormone related protein (PTHrP) and parathyroid hormone receptors (PTHR) was responsible for the corrective effect of periosteal stripping. Twelve 3 months old lambs underwent periosteal stripping of the distal lateral radius and tibia on one side. The contralateral side served as non-operated controls. Two animals each group were sacrificed at 2, 6, 10, 14, 18 and 21 days after surgery and the growth plates with minimal adjacent bone tissue were harvested for histological investigations. After decalcification, paraffin-embedded sections with routine hematoxylin-eosin stains were prepared to assess morphology and length of growth plates, whereas immunohistochemistry of Ihh, PTHrP, PTHR and the two cytokines fibroblast- (FGF) and transforming growth factor (TGF) was performed to study different protein expression between operated limbs and controls. The results indicate that periosteal stripping caused an up-regulation of Ihh in the early pre- and hypertrophic zone of the growth plate, followed by an increase of PTHrP mainly in the perichondrium, while an increase of PTHR was noticed in all zones, although highest in the perichondrium and hypertrophic zones. The growth factors FGF and TGF were upregulated in all zones, but FGF in response to periosteal stripping was more intensely expressed in the proliferative zone and the highest peak of TGF was found in the perichondrium. Length measurements of the various growth zones revealed significant negative correlations between the proliferative and pre-and hypertrophic zones, indicating that indeed a negative feed back loop after periosteal stripping exists coupled by the Ihh/PTHrP/PTHR cascade.The hypothesis that periosteal stripping had an effect on the Ihh/PTHrP/PTHR related feedback loop in epiphyseal growth was confirmed in this experimental study in lambs. Since these mechanisms are very basic and similar in most species, it can be safely assumed that the effects in foals are similar. In fact, the asymmetric mechanical load in animals suffering from axis deviation may even increase the enhancing effect of length correction