title: Pain reactivity and plasma beta-endorphin in children and adolescents with autistic disorder.
abstract: BACKGROUND
  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 beta-endorphin levels and their relationship in a large group of individuals with autism.
  
  
  RESULTS
  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 beta-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 (Delta 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 beta-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
  The greater heart rate response to venepuncture and the elevated plasma beta-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.
authors.affiliation: Laboratoire Psychologie de la Perception, Université Paris Descartes, UMR 8158 CNRS, Paris, France. s.tordjman@ch-guillaumeregnier.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tordjman
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Michel
authors.initials: M
authors.lastname: Botbol
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brailly-Tabard
authors.forename: Fernando
authors.initials: F
authors.lastname: Perez-Diaz
authors.forename: Rozenn
authors.initials: R
authors.lastname: Graignic
authors.forename: Michèle
authors.initials: M
authors.lastname: Carlier
authors.forename: Gérard
authors.initials: G
authors.lastname: Schmit
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Rolland
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonnot
authors.forename: Séverine
authors.initials: S
authors.lastname: Trabado
authors.forename: Pierre
authors.initials: P
authors.lastname: Roubertoux
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bronsard
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000097:blood / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D010146:Pain / Q000503:physiopathology*; D001615:beta-Endorphin / Q000097:blood*
chemical_list: D001615:beta-Endorphin
references.citation: Psychiatry Res. 1992 Feb;41(2):179-86
references.pmid: 1315442
references.citation: J Dev Behav Pediatr. 1999 Aug;20(4):235-43
references.pmid: 10475598
references.citation: Clin J Pain. 1996 Jun;12(2):135-41
references.pmid: 8776553
references.citation: Psychopharmacol Bull. 1993;29(2):221-7
references.pmid: 8290669
references.citation: J Pers. 1951 Jun;19(4):359-75
references.pmid: 14874176
references.citation: BMJ. 1996 Sep 28;313(7060):796
references.pmid: 8842075
references.citation: Pain. 1992 Jan;48(1):45-52
references.pmid: 1738574
references.citation: Pharmacol Biochem Behav. 1978 Aug;9(2):213-20
references.pmid: 568801
references.citation: Clin Pediatr (Phila). 1976 Dec;15(12):1114-9
references.pmid: 991529
references.citation: J Autism Dev Disord. 1994 Oct;24(5):659-85
references.pmid: 7814313
references.citation: Psychiatry Res. 1995 Oct 16;58(3):191-201
references.pmid: 8570775
references.citation: Am J Ment Defic. 1983 Sep;88(2):177-86
references.pmid: 6638079
references.citation: Dev Med Child Neurol. 1998 May;40(5):340-3
references.pmid: 9630262
references.citation: J Child Psychol Psychiatry. 1997 Sep;38(6):705-15
references.pmid: 9315980
references.citation: Neuroendocrinology. 1992 Sep;56(3):419-28
references.pmid: 1331840
references.citation: J Dev Behav Pediatr. 1999 Aug;20(4):244-52
references.pmid: 10475599
references.citation: Lancet. 1994 Aug 27;344(8922):615
references.pmid: 7914981
references.citation: J Dev Behav Pediatr. 1999 Aug;20(4):228-34
references.pmid: 10475597
references.citation: Psychopharmacology (Berl). 1984;82(4):368-70
references.pmid: 6427830
references.citation: Biol Psychiatry. 1983 Jan;18(1):99-101
references.pmid: 6299409
references.citation: Appl Res Ment Retard. 1983;4(1):5-11
references.pmid: 6870234
references.citation: Clin J Pain. 2009 Mar-Apr;25(3):244-52
references.pmid: 19333176
references.citation: Clin J Pain. 1999 Mar;15(1):13-23
references.pmid: 10206563
references.citation: J Autism Dev Disord. 1991 Mar;21(1):83-7
references.pmid: 2037552
references.citation: J Autism Dev Disord. 1997 Apr;27(2):155-63
references.pmid: 9105966
references.citation: Mol Psychiatry. 2001 Jul;6(4):434-9
references.pmid: 11443529
references.citation: Med Hypotheses. 1997 May;48(5):413-4
references.pmid: 9185129
references.citation: Arch Gen Psychiatry. 1985 Aug;42(8):780-3
references.pmid: 4015322
references.citation: Am J Ment Retard. 1994 Mar;98(5):619-31
references.pmid: 8192908
references.citation: Am J Ment Defic. 1985 Sep;90(2):124-9
references.pmid: 2996351
references.citation: Biol Psychiatry. 1990 Nov 1;28(9):773-93
references.pmid: 2175218
references.citation: Brain Dev. 1990;12(1):88-92
references.pmid: 2344033
references.citation: Psychopharmacol Bull. 1990;26(1):130-5
references.pmid: 2196621
references.citation: Isr J Med Sci. 1990 May;26(5):275-7
references.pmid: 2380025
references.citation: Biol Psychiatry. 1999 Jan 15;45(2):158-63
references.pmid: 9951562
references.citation: J Psychiatr Pract. 2006 Mar;12(2):90-102
references.pmid: 16728905
references.citation: Pain. 2000 Jan;84(1):65-75
references.pmid: 10601674
references.citation: J Autism Child Schizophr. 1978 Dec;8(4):477-9
references.pmid: 730668
references.citation: Clin J Pain. 2004 Mar-Apr;20(2):88-97
references.pmid: 14770048
references.citation: J Am Acad Child Adolesc Psychiatry. 1988 Jul;27(4):430-3
references.pmid: 2972691
references.citation: Neuropsychobiology. 1997;35(1):1-4
references.pmid: 9018016
references.citation: Brain Res Bull. 1978 Nov-Dec;3(6):663-7
references.pmid: 318190
references.citation: Encephale. 1999 Mar-Apr;25(2):122-34
references.pmid: 10370885
references.citation: Cephalalgia. 1999 Oct;19(8):725-7
references.pmid: 10570727
references.citation: Arch Gen Psychiatry. 1995 Sep;52(9):766-73
references.pmid: 7654128
references.citation: J Autism Dev Disord. 1987 Jun;17(2):201-16
references.pmid: 3038836
references.citation: Am J Psychiatry. 1994 Dec;151(12):1797-801
references.pmid: 7977888
references.citation: Pediatr Neurol. 1987 Mar-Apr;3(2):83-6
references.pmid: 2977280
references.citation: J Autism Dev Disord. 1992 Jun;22(2):309-19
references.pmid: 1345670
references.citation: Kurume Med J. 1993;40(4):233-41
references.pmid: 8007632
references.citation: Neuroendocrinology. 1989 Oct;50(4):372-81
references.pmid: 2812272
references.citation: J Psychiatr Res. 1994 Mar-Apr;28(2):109-22
references.pmid: 7932274
references.citation: Life Sci. 1979 Nov 12;25(20):1755-60
references.pmid: 575184
references.citation: J Pediatr Psychol. 2000 Jul-Aug;25(5):301-8
references.pmid: 10880060
references.citation: Eur Neuropsychopharmacol. 1999 Jun;9(4):361-6
references.pmid: 10422898