A practical guide and perspectives on the use of experimental pain modalities with children and adolescents

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

• 1  Milgram S. Behavioral study of obedience. J. Abnorm. Soc. Psychol.67(4),371–378 (1963).
  CASGoogle Scholar
• 2  King S, Chambers CT, Huguet A et al. The epidemiology of chronic pain in children and adolescents revisited: a systematic review. Pain152(12),2729–2738 (2011).
  MedlineGoogle Scholar
• 3  Stevens BJ, Abbott LK, Yamada J et al. Epidemiology and management of painful procedures in children in Canadian hospitals. CMAJ183(7),E403–E410 (2011).
  MedlineGoogle Scholar
• 4  von Baeyer CL, Baskerville S, McGrath PJ. Everyday pain in three-to five-year-old children in day care. Pain Res. Manag.3(2),111–116 (1998).
  Google Scholar
• 5  Charlton JE. Core Curriculum for Professional Education in Pain. IASP Press, Seattle, WA, USA (2005).
  Google Scholar
• 6  Noel M, Birnie KA. Ethical challenges in pediatric pain research. Pediatr. Pain Lett.12,1–5 (2010).
  Google Scholar
• 7  Birnie KA, Noel M, Chambers CT, von Baeyer CL, Fernandez CV. The cold pressor task: is it an ethically acceptable pain research method in children? J. Pediatr. Psychol.36(10),1071–1081 (2011).
  MedlineGoogle Scholar
• 8  Fisher CB, Kornetsky SZ, Prentice ED. Determining risk in pediatric research with no prospect of direct benefit: time for a national consensus on the interpretation of federal regulations. Am. J. Bioeth.7(3),5–10 (2007).
  MedlineGoogle Scholar
• 9  Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council. Tri-council policy statement: ethical conduct for research involving humans (2010). http://pre.ethics.gc.ca/pdf/eng/tcps2/TCPS_2_FINAL_Web.pdf
  Google Scholar
• 10  World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects (2008). www.wma.net/en/30publications/10policies/b3/17c.pdf
  Google Scholar
• 11  Myers CD, Tsao JC, Glover DA, Kim SC, Turk N, Zeltzer LK. Sex, gender, and age: contributions to laboratory pain responding in children and adolescents. J. Pain7(8),556–564 (2006).
  MedlineGoogle Scholar
• 12  Dufton LM, Konik B, Colletti R et al. Effects of stress on pain threshold and tolerance in children with recurrent abdominal pain. Pain136(1–2),38–43 (2008).
  MedlineGoogle Scholar
• 13  Caes L, Vervoort T, Eccleston C, Vandenhende M, Goubert L. Parental catastrophizing about child’s pain and its relationship with activity restriction: the mediating role of parental distress. Pain152(1),212–222 (2011).
  Medline CASGoogle Scholar
• 14  Caes L, Vervoort T, Trost Z, Goubert L. Impact of parental catastrophizing and contextual threat on parents’ emotional and behavioral responses to their child’s pain. Pain153(3),687–695 (2012).
  MedlineGoogle Scholar
• 15  Chambers CT, Craig KD, Bennett SM. The impact of maternal behavior on children’s pain experiences: an experimental analysis. J. Pediatr. Psychol.27(3),293–301 (2002).
  MedlineGoogle Scholar
• 16  Walker LS, Williams SE, Smith CA, Garber J, Van Slyke DA, Lipani TA. Parent attention versus distraction: impact on symptom complaints by children with and without chronic functional abdominal pain. Pain122(1–2),43–52 (2006).
  MedlineGoogle Scholar
• 17  Lu Q, Tsao JC, Myers CD, Kim SC, Zeltzer LK. Coping predictors of children’s laboratory-induced pain tolerance, intensity, and unpleasantness. J. Pain8(9),708–717 (2007).
  MedlineGoogle Scholar
• 18  Dahlquist LM, Weiss KE, Law EF et al. Effects of videogame distraction and a virtual reality type head-mounted display helmet on cold pressor pain in young elementary school-aged children. J. Pediatr. Psychol.35(6),617–625 (2010).
  MedlineGoogle Scholar
• 19  Moore DJ, Keogh E, Crombez G, Eccleston C. Methods for studying naturally occurring human pain and their analogues. Pain154(2),190–199 (2013).
  MedlineGoogle Scholar
• 20  Feuerstein M, Barr RG, Francoeur TE, Houle M, Rafman S. Potential biobehavioral mechanisms of recurrent abdominal pain in children. Pain13(3),287–298 (1982).
  Medline CASGoogle Scholar
• 21  Neziri AY, Curatolo M, Nüesch E et al. Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment. Pain152(5),1146–1155 (2011).
  MedlineGoogle Scholar
• 22  Nielsen CS, Staud R, Price DD. Individual differences in pain sensitivity: measurement, causation, and consequences. J. Pain10(3),231–237 (2009).
  MedlineGoogle Scholar
• 23  Blankenburg M, Boekens H, Hechler T et al. Reference values for quantitative sensory testing in children and adolescents: developmental and gender differences of somatosensory perception. Pain149,76–88 (2010).▪▪ Establishes feasibility and reference values for pressure and thermal pain stimuli with children and adolescents as part of the quantitative sensory testing protocol.
  Medline CASGoogle Scholar
• 24  Wollgarten-Hadamek I, Hohmeister J, Zohsel K, Flor H, Hermann C. Do school-aged children with burn injuries during infancy show stress-induced activation of pain inhibitory mechanisms? Eur. J. Pain15(4),423.e1–10 (2011).
  Google Scholar
• 25  Reid GJ, McGrath PJ, Lang BA. Parent–child interactions among children with juvenile fibromyalgia, arthritis, and healthy controls. Pain113(1–2),201–210 (2005).
  MedlineGoogle Scholar
• 26  Hines EA Jr. Reaction of the blood pressure of 400 school children to a standard stimulus. JAMA108(15),1249–1250 (1937).
  Google Scholar
• 27  Zeltzer LK, Fanurik D, LeBaron S. The cold pressor pain paradigm in children: feasibility of an intervention model (part II). Pain37(3),305–313 (1989).
  Medline CASGoogle Scholar
• 28  LeBaron S, Zeltzer L, Fanurik D. An investigation of cold pressor pain in children (part I). Pain37(2),161–171 (1989).
  Medline CASGoogle Scholar
• 29  Birnie KA, Petter M, Boerner KE, Noel M, Chambers CT. Contemporary use of the cold pressor task in pediatric pain research: a systematic review of methods. J. Pain13(9),817–826 (2012).▪ Systematic review of methodological variability in cold pressor task use with pediatric samples and provides an update to earlier guidelines.
  MedlineGoogle Scholar
• 30  von Baeyer CL, Piira T, Chambers CT, Trapanotto M, Zeltzer LK. Guidelines for the cold pressor task as an experimental pain stimulus for use with children. J. Pain6(4),218–227 (2005).▪▪ Guidelines directing standardized and ethical use of the cold pressor task with children.
  MedlineGoogle Scholar
• 31  Trapanotto M, Pozziani G, Perissinotto E, Barbieri S, Zacchello F, Benini F. The cold pressor test for the pediatric population: refinement of procedures, development of norms, and study of psychological variables. J. Pediatr. Psychol.34(7),749–759 (2009).
  MedlineGoogle Scholar
• 32  Tsao JC, Evans S, Seidman LC, Zeltzer LK. Experimental pain responses in children with chronic pain and in healthy children: how do they differ? Pain Res. Manag.17(2),103–109 (2012).
  MedlineGoogle Scholar
• 33  Williams AE, Heitkemper M, Self MM, Czyzewski DI, Shulman RJ. Endogenous inhibition of somatic pain is impaired in girls with irritable bowel syndrome compared with healthy girls. J. Pain14(9),921–930 (2013).
  MedlineGoogle Scholar
• 34  Moon EC, Chambers CT, McGrath PJ. ‘He says, she says’: a comparison of fathers’ and mothers’ verbal behavior during child cold pressor pain. J. Pain12(11),1174–1181 (2011).
  MedlineGoogle Scholar
• 35  Noel M, Chambers CT, McGrath PJ, Klein RM, Stewart SH. The influence of children’s pain memories on subsequent pain experience. Pain153(8),1563–1572 (2012).
  MedlineGoogle Scholar
• 36  Petter M, Chambers CT, MacLaren Chorney J. The effects of mindfulness-based attention on cold pressor pain in children. Pain Res. Manag.18(1),39–45 (2013).
  MedlineGoogle Scholar
• 37  Vervoort T, Trost Z, Van Ryckeghem DM. Children’s selective attention to pain and avoidance behaviour: the role of child and parental catastrophizing about pain. Pain154(10),1979–1988 (2013).
  MedlineGoogle Scholar
• 38  Schmitz AK, Vierhaus M, Lohaus A. Pain tolerance in children and adolescents: sex differences and psychosocial influences on pain threshold and endurance. Eur. J. Pain17(1),124–131 (2013).
  MedlineGoogle Scholar
• 39  Evans S, Seidman LC, Tsao JC, Lung KC, Zeltzer LK, Naliboff BD. Heart rate variability as a biomarker for autonomic nervous system response differences between children with chronic pain and healthy control children. J. Pain Res.6,449–457 (2013).
  MedlineGoogle Scholar
• 40  Dahlquist LM, McKenna KD, Jones KK, Dillinger L, Weiss KE, Ackerman CS. Active and passive distraction using a head-mounted display helmet: effects on cold pressor pain in children. Health Psychol.26(6),794–801 (2007).
  MedlineGoogle Scholar
• 41  Dahlquist LM, Weiss KE, Clendaniel LD, Law EF, Ackerman CS, McKenna KD. Effects of videogame distraction using a virtual reality type head-mounted display helmet on cold pressor pain in children. J. Pediatr. Psychol.34(5),574–584 (2009).
  MedlineGoogle Scholar
• 42  Wohlheiter KA, Dahlquist LM. Interactive versus passive distraction for acute pain management in young children: the role of selective attention and development. J. Pediatr. Psychol.38(2),202–212 (2013).
  MedlineGoogle Scholar
• 43  Stuber M, Hilber SD, Mintzer LL, Castaneda M, Glover D, Zeltzer L. Laughter, humor and pain perception in children: a pilot study. Evid. Based Complement Alternat. Med.6(2),271–276 (2009).
  MedlineGoogle Scholar
• 44  Tsao JC, Myers CD, Craske MG, Bursch B, Kim SC, Zeltzer LK. Role of anticipatory anxiety and anxiety sensitivity in children’s and adolescents’ laboratory pain responses. J. Pediatr. Psychol.29(5),379–388 (2004).
  MedlineGoogle Scholar
• 45  Weiss KE, Dahlquist LM, Wohlheiter K. The effects of interactive and passive distraction on cold pressor pain in preschool-aged children. J. Pediatr. Psychol.36(7),816–826 (2011).
  MedlineGoogle Scholar
• 46  Mitchell LA, MacDonald RA, Brodie EE. Temperature and the cold pressor test. J. Pain5(4),233–237 (2004).
  MedlineGoogle Scholar
• 47  Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain intensity rating scales. Pain152(10),2399–2404 (2011).
  MedlineGoogle Scholar
• 48  Hirsch MS, Liebert RM. The physical and psychological experience of pain: the effects of labeling and cold pressor temperature on three pain measures in college women. Pain77(1),41–48 (1998).
  Medline CASGoogle Scholar
• 49  Williams DA, Thorn BE. Can research methodology affect treatment outcome? A comparison of two cold pressor test paradigms. Cognit. Ther. Res.10(5),539–545 (1986).
  Google Scholar
• 50  Jackson T, Pope L, Nagasaka T, Fritch A, Iezzi T, Chen H. The impact of threatening information about pain on coping and pain tolerance. Br. J. Health Psychol.10,441–451 (2005).
  MedlineGoogle Scholar
• 51  Wolf S, Hardy JD. Studies on pain. Observations on pain due to local cooling and on factors involved in the ‘cold pressor’ effect. J. Clin. Invest.20(5),521–533 (1941).
  Medline CASGoogle Scholar
• 52  Coldwell SE, Kaakko T, Gärtner-Makihara AB et al. Temporal information reduces children’s pain reports during a multiple-trial cold pressor procedure. Behav. Ther.33(1),45–63 (2003).
  Google Scholar
• 53  Tsao JC, Glover DA, Bursch B, Ifekwunigwe M, Zeltzer LK. Laboratory pain reactivity and gender: relationship to school nurse visits and school absences. J. Dev. Behav. Pediatr.23(4),217–224 (2002).
  MedlineGoogle Scholar
• 54  Walker LS, Williams SE, Smith CA et al. Validation of a symptom provocation test for laboratory studies of abdominal pain and discomfort in children and adolescents. J. Pediatr. Psychol.31(7),703–713 (2006).▪▪ Describes the development and use of the water load symptom provocation test with children.
  MedlineGoogle Scholar
• 55  Mertz H, Naliboff B, Munakata J, Niazi N, Mayer EA. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology109(1),40–52 (1995).
  Medline CASGoogle Scholar
• 56  Koch KL, Bingaman S, Muth E, Ouyang A. Effects of physiological gastric distention on nausea, stomach fullness, satiety and gastric myoelectrical activity in patients with irritable bowel syndrome. Gastroenterology4,A763 (1997).
  Google Scholar
• 57  Sood MR, Schwankovsky LM, Rowhani A et al. Water load test in children. J. Pediatr. Gastroenterol. Nutr.35(2),199–201 (2002).
  MedlineGoogle Scholar
• 58  Schurman JV, Friesen CA, Andre L et al. Diagnostic utility of the water load test in children with chronic abdominal pain. J. Pediatr. Gastroenterol. Nutr.44(1),51–57 (2007).
  MedlineGoogle Scholar
• 59  Williams SE, Blount RL, Walker LS. Children’s pain threat appraisal and catastrophizing moderate the impact of parent verbal behavior on children’s symptom complaints. J. Pediatr. Psychol.36(1),55–63 (2011).
  MedlineGoogle Scholar
• 60  Anderson JL, Acra S, Bruehl S, Walker LS. Relation between clinical symptoms and experimental visceral hypersensitivity in pediatric patients with functional abdominal pain. J. Pediatr. Gastroenterol. Nutr.47(3),309–315 (2008).▪ Provides evidence for the relationship of pain responding during the water load symptom provocation test to clinical pain and real-world outcomes.
  MedlineGoogle Scholar
• 61  Zohsel K, Hohmeister J, Flor H, Hermann C. Somatic pain sensitivity in children with recurrent abdominal pain. Am. J. Gastroenterol.103(6),1517–1523 (2008).
  MedlineGoogle Scholar
• 62  Hermann C, Hohmeister J, Demirakça S, Zohsel K, Flor H. Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain125(3),278–285 (2006).
  MedlineGoogle Scholar
• 63  Meier PM, Berde CB, DiCanzio J, Zurakowski D, Sethna NF. Quantitative assessment of cutaneous thermal and vibration sensation and thermal pain detection thresholds in healthy children and adolescents. Muscle Nerve24(10),1339–1345 (2001).
  Medline CASGoogle Scholar
• 64  Walker LS, Sherman AL, Bruehl S, Garber J, Smith CA. Functional abdominal pain patient subtypes in childhood predict functional gastrointestinal disorders with chronic pain and psychiatric comorbidities in adolescence and adulthood. Pain153(9),1798–1806 (2012).
  MedlineGoogle Scholar
• 65  Ruscheweyh R, Stumpenhorst F, Knecht S, Marziniak M. Comparison of the cold pressor test and contact thermode-delivered cold stimuli for the assessment of cold pain sensitivity. J. Pain11(8),728–736 (2010).
  MedlineGoogle Scholar
• 66  Moloney NA, Hall TM, Doody CM. Reliability of thermal quantitative sensory testing: a systematic review. J. Rehabil. Res. Dev.49(2),191–207 (2012).
  MedlineGoogle Scholar
• 67  Bar-Shalita T, Vatine JJ, Seltzer Z, Parush S. Psychophysical correlates in children with sensory modulation disorder (SMD). Physiol. Behav.98(5),631–639 (2009).
  Medline CASGoogle Scholar
• 68  Hohmeister J, Demirakça S, Zohsel K, Flor H, Hermann C. Responses to pain in school-aged children with experience in a neonatal intensive care unit: cognitive aspects and maternal influences. Eur. J. Pain13(1),94–101 (2009).
  MedlineGoogle Scholar
• 69  Goubert L, Vervoort T, Cano A, Crombez G. Catastrophizing about their children’s pain is related to higher parent-child congruency in pain ratings: an experimental investigation. Eur. J. Pain13(2),196–201 (2009).
  Medline CASGoogle Scholar
• 70  Payne LA, Seidman LC, Lung KC, Zeltzer LK, Tsao JC. Relationship of neuroticism and laboratory pain in healthy children: does anxiety sensitivity play a role? Pain154(1),103–109 (2013).
  MedlineGoogle Scholar
• 71  Hashkes PJ, Friedland O, Jaber L, Cohen HA, Wolach B, Uziel Y. Decreased pain threshold in children with growing pains. J. Rheumatol.31(3),610–613 (2004).
  MedlineGoogle Scholar
• 72  Duarte MA, Goulart EM, Penna FJ. Pressure pain threshold in children with recurrent abdominal pain. J. Pediatr. Gastroenterol. Nutr.31(3),280–285 (2000).
  Medline CASGoogle Scholar
• 73  Chaves TC, Nagamine HM, de Sousa LM, de Oliveira AS, Regalo SC, Grossi DB. Differences in pain perception in children reporting joint and orofacial muscle pain. J. Clin. Pediatr. Dent.37(3),321–327 (2013).
  Medline CASGoogle Scholar
• 74  Soee AB, Skov L, Kreiner S, Tornoe B, Thomsen LL. Pain sensitivity and pericranial tenderness in children with tension-type headache: a controlled study. J. Pain Res.6,425–434 (2013).
  MedlineGoogle Scholar
• 75  Wolfe F, Smythe HA, Yunus MB et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Arthritis Rheum.33(2),160–172 (1990).
  Medline CASGoogle Scholar
• 76  Smith MT, Wickwire EM, Grace EG et al. Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder. Sleep32(6),779–790 (2009).
  MedlineGoogle Scholar
• 77  Fernández-de-Las-Peñas C, Cuadrado ML, Arendt-Nielsen L, Ge HY, Pareja JA. Increased pericranial tenderness, decreased pressure pain threshold, and headache clinical parameters in chronic tension-type headache patients. Clin. J. Pain23(4),346–352 (2007).
  MedlineGoogle Scholar
• 78  Riley JL, Robinson ME, Wise EA, Myers CD, Fillingim RB. Sex differences in the perception of noxious experimental stimuli: a meta-analysis. Pain74(2–3),181–187 (1998).
  MedlineGoogle Scholar
• 79  Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): Its relevance for acute and chronic pain states. Curr. Opin. Anaesthesiol.23(5),611–615 (2010).
  MedlineGoogle Scholar
• 80  Cathcart S, Petkov J, Winefield AH, Lushington K, Rolan P. Central mechanisms of stress-induced headache. Cephalalgia30(3),285–295 (2010).
  Medline CASGoogle Scholar
• 81  Seifert F, Kiefer G, DeCol R, Schmelz M, Maihöfner C. Differential endogenous pain modulation in complex-regional pain syndrome. Brain132,788–800 (2009).
  MedlineGoogle Scholar
• 82  Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J. Pain13,936–944 (2012).
  MedlineGoogle Scholar
• 83  Tsao JC, Seidman LC, Evans S, Lung KC, Zeltzer LK, Naliboff BD. Conditioned pain modulation in children and adolescents: effects of sex and age. J. Pain14(6),558–567 (2013).▪ Provides an example of conditioned pain modulation in children using pressure pain and a cold water conditioning stimulus.
  MedlineGoogle Scholar
• 84  Goffaux P, Lafrenaye S, Morin M, Patural H, Demers G, Marchand S. Preterm births: can neonatal pain alter the development of endogenous gating systems? Eur. J. Pain12(7),945–951 (2008).
  MedlineGoogle Scholar
• 85  van Wijk G, Veldhuijzen DS. Perspective on diffuse noxious inhibitory controls as a model of endogenous pain modulation in clinical pain syndromes. J. Pain11(5),408–419 (2010).
  MedlineGoogle Scholar
• 86  Nir RR, Yarnitsky D, Honigman L, Granot M. Cognitive manipulation targeted at decreasing the conditioning pain perception reduces the efficacy of conditioned pain modulation. Pain153(1),170–176 (2012).
  MedlineGoogle Scholar
• 87  US Department of Health and Human Services. Protection of human subjects research 45 CFR 46.408 (2009). www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.408
  Google Scholar
• 88  Wendler DS. Assent in paediatric research: theoretical and practical considerations. J. Med. Ethics32(4),229–234 (2006).
  Medline CASGoogle Scholar
• 89  Tait AR, Voepel-Lewis T, Malviya S. Participation of children in clinical research: factors that influence a parent’s decision to consent. Anesthesiology99,819–825 (2003).
  MedlineGoogle Scholar
• 90  Chang PF, Arendt-Nielsen L, Chen AC. Dynamic changes and spatial correlation of EEG activities during cold pressor test in man. Brain Res. Bull.57(5),667–675 (2002).
  MedlineGoogle Scholar
• 91  Diatchenko L, Nackley AG, Slade GD et al. Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain125(3),216–224 (2006).
  Medline CASGoogle Scholar
• 92  Mogil JS. Pain genetics: past, present and future. Trends Genet.28(6),258–266 (2012).
  Medline CASGoogle Scholar
• 93  Reimann F, Cox JJ, Belfer I et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc. Natl Acad. Sci. USA107(11),5148–5153 (2010).
  Medline CASGoogle Scholar
• 94  Rahim-Williams B, Riley JL, Williams KK et al. A quantitative review of ethnic group differences in experimental pain response: do biology, psychology, and culture matter? Pain Med.13,522–540 (2012).
  MedlineGoogle Scholar
• 95  Allen LB, Lu Q, Tsao JCI et al. Sex differences in the association between cortisol concentrations and laboratory pain responses in healthy children. Gender Med.6,193–207 (2009).
  MedlineGoogle Scholar
• 96  Evans S, Lu Q, Tsao JCI et al. The role of coping and race in healthy children’s experimental pain responses. J. Pain Manag.1,151–162 (2008).
  MedlineGoogle Scholar
• 97  Keenan K, Hipwell AE, Hinze AE et al. The association of pain and depression in preadolescent girls: moderation by race and pubertal stage. J. Pediatr. Psychol.34,727–737 (2009).
  MedlineGoogle Scholar
• 98  Wilson AC, Holley AL, Palermo TM. Applications of laboratory pain methodologies in research with children and adolescents: emerging research trends. Pain154(8),1166–1169 (2013).▪ Recent discussion of future directions for pediatric experimental pain research.
  MedlineGoogle Scholar