Infants who are born prematurely and who have experienced at least 40 days of intensive or special care also have increased brain neuronal responses to noxious stimuli compared to he althy new- borns at the same postmenstrual age. Evoked potentials generated by noxious clin ically-essential heel lances are signifi cantly larger in prematurely-born infants, while r esponses to non-noxious touch stimuli are unaff ected, suggesting a functional change in pa in processing in the brain (Slater et al., 2010b). FMRI of cerebral pain responses in a sim ilar cohort of preterm infants when they have reached school-age (11 \200\22316 years) show that aside from more gen- eral neurodevelopmental consequences, repeated neonatal nocic- e ptive input may result in continued increased sensitivity in central pain pathways into ado lescence. Tonic heat stimuli (of individually adjusted moderate pain intensity) applied to the ex-preterm chil- dren causes signifi cant activation in the thalamus, anterior cingu- l ate cortex, cerebellum, basal ganglia, and PAG that is not observed in full-term hospitaliz ed children or controls. Th e preterms also show signifi cantly higher activation in the S1 , anterior cingulate cortex, and insula than controls. Th is exaggerated brain response is pain specifi c and is not observed during non-painful warmth stimulation (Hohmeister et al. , 2010) Neonatal pain has also been shown to infl uence the generation of new neurons in the dentat e gyrus region of the hippocampus. Rat pups receiving intraplantar injections of the painfu l infl am- matory agent complete Freund \200\231s adjuvant, on P8, had more BrdU- labeled c ells and a higher density of cells expressing doublecortin, both measures of newborn neuron s, in the subgranular zone of the dentate gyrus, thought to be involved in memory formation (Leslie et al., 2011). Th ere is also evidence that neonatal intensive care can alter endog- enous descending cont rol systems. Children, aged between 7 and 11 years, divided into term, preterm exposed to n umerous painful interventions, or preterm exposed to few painful interventions, have compar able pain thresholds but diff er in their responses to condi- tioning cold stimulation. Th us while cold stimulation signifi cantly increases heart rate and decreases thermal pain se nsitivity of term- born children and \200\230preterm less pain \200\231 children, changes in heart rate and pain sensitivity in response to conditioning cold stimulation were not ob served in \200\230preterm more pain \200\231 children. Th ese results suggest that endogen ous pain modulatory mechanisms are not as well developed as those of children not exposed t o noxious insult at birth (Goff aux et al., 2008; Wollgarten-Hadamek et al., 2011) Descending pain control systems in the brainstem can also be infl uenced by early pain expe rience. Infl ammatory pain induced by intraplantar carrageenan at birth induces signifi can t changes in the brainstem endogenous opioid system into adulthood, namely increased beta-e ndorphin and met/leu-enkephalin protein levels and decreased opioid receptor expression in the PAG. Th ese long- lasting alterations in endogenous opioid tone are likely to aff ect l ater pain sensitivity (Laprairie and Murphy, 2009). Th is is supported by the observation t hat focal electrical stimulation of the RVM in adult animals treated neonatally with carrag eenan produced sig- nifi cantly greater descending inhibition of nociceptive responses to n oxious thermal stimuli applied to the hindpaws and the tail, indicating that neonatal tissu e injury and infl ammation produces lasting alterations in descending modulatory systems th at modify nociceptive processing (Zhang et al., 2010). Evidence in human brain \200\224pediatric chronic pain Evidence suggests that central chang es in the brain can occur in older children who develop chronic pain syndromes. Children wi th migraine when undertaking an experimental attentional task, display EEG activity associa ted with an automatic attentional bias towards painful and potentially painful somatosensor y stimuli, perhaps due to alterations in connectivity within the limbic system (Zohsel et a l., 2008). Evidence in human brain \200\224e \200 ects of neonatal intensive care Th e developmental plasticity observed in laboratory animals is sup- ported by structural and functional evide nce of changes in the human infant brain following repeated noxious stimulation. Structural MRI studies suggest that procedural pain in the neonatal intensive care CNS activation to sensory stimulation in pediatric patients (9 \200\22318 years) with compl ex regional pain syndrome (CRPS) aff ecting SECTION 2 biological basis of pediatric pain 80 the lower extremity also reveals changes. In an fMRI study each patient underwent two scann ing sessions: once during an active period of pain (CRPS(+)), and once aft er symptomatic r ecovery (CRPS( \210\222 ). In each session, mechanical (brush) and thermal (cold) stimuli were applied to the aff ected region of the involved limb and the corresponding mirror regi on of the unaff ected limb. Several interesting observations were made in this study but no tably in the CRPS( \210\222 ) state, signifi cant activation diff erences persist despite nearly complete elimination of evoked pain suggesting prolonged changes in CNS pain circuit ry in pediatric patients with CRPS that outlast the illness itself (Lebel et al., 2008). Fitzgerald, M. and Koltzenburg, M. (1986). Th e functional development of descending inhibi tory pathways in the dorsolateral funiculus of the newborn rat spinal cord. Brain Res, 389 , 261 \200\223270 . Fransson, P., Aden, U., Blennow, M., and Lagercrantz, H. (2011). Th e functional architectu re of the infant brain as revealed by resting-state fMRI. Cereb Cortex, 21 (1), 145 \200 \223154 . Gauriau, C. and Bernard, J. F . (2004). A comparative reappraisal of projections from the s uperfi cial laminae of the dorsal horn in the rat: the forebrain. J Comp Neurol, 468 (1), 2 4 \200\22356 . Goff aux, P., Lafrenaye, S., Morin, M., Patural, H., Demers, G., and Marchand, S . (2008). Preterm births: can neonatal pain alter the development of endogenous gating systems? Eur J Pain , 12 (7), 945 \200\223951 . Hathway, G. J., Koch, S., Low, L., and Fitzgerald, M. (2009). The changing balance of brain stem-spinal cord modulation of pain processing over the first weeks of rat postnatal life. J Physiol, 587 (Pt 12), 2927 \200\2232935 . Th ere is an urgent need for more investigative studies of pain processing in the brains of children. Despite the ethical and prac- tical challenges that such studies present, it is important to allow children to participate in well-designed research studies so that they c an benefi t from research advances to the same degree as adult populations (Sava et al., 20 09). Hathway, G. J., Vega-Avelaira, D., and Fitzgerald, M. (2012). A critical period in the supr aspinal control of pain: opioid-dependent changes in brainstem rostroventral medulla functi on in preadolescence. Pain, 153(4), 775 \200\223783. References Apkarian, A. V., Bushnell, M. C., Treede, R.-D., and Zubieta, J.-K. (2005). Huma n brain mechanisms of pain perception and regulation in health and disease. Eur J Pain , 9, 463 \200\223484 . Heinricher, M. M., Tavares, I., Leith, J. L., and Lumb, B. M . (2009). Descending control o f nociception: specifi city, recruitment and plasticity. Brain Res Rev, 60 (1), 214 \200 \223225 . Hohmeister, J., Kroll, A., Wollgarten-Hadamek, I., Zohsel, K., Demirak a, S., Flor, H., et al . (2010). Cerebral processing of pain in school-aged children with neonatal nocicepti ve input: an exploratory fMRI study. Pain , 150 (2), 257 \200\223267 . Arichi, T., Moraux, A., Melendez, A., Doria, V., Groppo, M., Merchant, N., et al. (2010). S omatosensory cortical activation identifi ed by functional MRI in preterm and term infants. Neuroimage, 49 (3), 2063 \200\2232071 . Armstrong-James, M. (1975). The functional status and columnar organization of single cells responding to cutaneous stimulation in neonatal r at somatosensory cortex S1. J Physiol, 246 (3), 501 \200\223538 . Laprairie, J. L. and Murphy, A. Z . (2009). Neonatal injury alters adult pain sensitivity b y increasing opioid tone in the periaqueductal gray. Front Behav Neurosci, 3 , 31 . Lebel, A., Becerra, L., Wallin, D., Moulton, E. A., Morris, S., Pendse, G., et al . (2008). fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pai n syndrome in children. Brain, 131 , 1854 \200\2231879 . Barbaresi, P. (2010). Postnatal development of GABA-immunoreactive neurons and terminals in rat periaqueductal gray matter: a light and electron microscopic study. J Comp Neurol, 518 (12), 2240 \200\2232260 . Barr, G. A . (2011). Formalin-induced c-fos expression in the brain of infant Legrain, V., Iannetti, G. D., Plaghki, L., and Mouraux, A . (2011). Th e pain matrix reload ed: a salience detection system for the body. Prog Neurobiol , 93 (1), 111 \200\223124 . rats. J Pain, 12 (2), 263 \200\223271 . Boucher, T., Jennings, E., and Fitzgerald, M. (1998). Th e onset of diff use noxious inhibi tory controls in postnatal rat pups: a C-Fos study. Neurosci Lett, 257 (1), 9 \200\22312 . Leslie, A. T., Akers, K. G., Martinez-Canabal, A., Mello, L. E., Covolan, L., and Guinsburg , R. (2011). Neonatal infl ammatory pain increases hippocampal neurogenesis in rat pups. Ne urosci Lett , 501 (2), 78 \200\22382 . Li, H. and Crair, M. C . (2011). How do barrels form in somatosensory cortex? Brummelte, S., Grunau, R. E., Chau, V., Poskitt, K. J., Brant. R., Vinall, J., et al . (201 2). Procedural pain and brain development in premature newborns. Ann Neurol , 71(3), 385 \200\223396. Ann N Y Acad Sci , 1225 , 119 \200\223129 . Chan, T., Kyere, K., Davis, B. R., Shemyakin, A., Kabitzke, P. A., Shair, H. N., et al . (2 011) . Th e role of the medial prefrontal cortex in innate fear regulation in infants, juve niles, and adolescents. J Neurosci. 31 (13), 4991 \200\2234999 . Low, L. A. and Fitzgerald, M. (2012). Acute pain and a motivational pathway in adult rats: infl uence of early life pain experience. PLoS ONE, 7(3), e34316. Oberlander, T. F., Grunau, R. E., Fitzgerald, C., and Whitfi eld, M. F. (2002). Does parenc hymal brain injury aff ect biobehavioral pain responses in very low birth weight infants at 32 weeks \200\231 postconceptional age? Pediatrics , 110 (3), 570 \200\223576 . Colonnese, M. and Khazipov, R. (2012). Spontaneous activity in developing sensory circuits: implications for resting state fMRI. Neuroimage , 62(4), 2212 \200\2232221. Davidson, S., Truong, H., and Giesler, G. J. Jr. (2010). Quantitative analysis of spinothal amic tract neurons in adult and developing mouse. J Comp Neurol , 518 (16), 3193 \200\22332 04 . Quairiaux, C., M gevand, P., Kiss, J. Z., and Michel, C. M . (2011). Functional developm ent of large-scale sensorimotor cortical networks in the brain. J Neurosci , 31 (26), 9574 \200\2239584 . Dubois, J., Dehaene-Lambertz, G., Perrin, M., Mangin, J. F., Cointepas, Y., Duchesnay, E., et al . (2008). Asynchrony of the early maturation of white matter bundles in healthy infan ts: quantitative landmarks revealed noninvasively by diff usion tensor imaging. Hum Brain M app, 29 (1), 14 \200\22327 . Eippert, F., Finsterbusch, J., Bingel, U., and B chel, C . (2009). Direct evidence for spinal cord involvement in placebo analgesia. Science, 326 (595 1), 404 . Sava, S., Lebel, A. A., Leslie, D. S., Drosos, A., Berde, C., Becerra, L., et al . (2009). Challenges of functional imaging research of pain in children. Mol Pain , 5 , 30 . Slater, R., Cantarella, A., Franck, L., Meek, J., and Fitzgerald, M. (2008). How well do cl inical pain assessment tools refl ect pain in infants? PLoS Med, 5 (6), e129 . Slater, R., Cantarella, A., Gallella, S., Worley, A., Boyd, S., Meek, J., et al . (2006). C ortical pain responses in human infants. J Neurosci , 26 (14), 3662 \200\2233666 Fabrizi, L., Slater, R., Worley, A., Meek, J., Boyd, S., Olhede, S., et al . (2011). A shif t in sensory processing that enables the developing human brain to discriminate touch from pain. Curr Biol , 21 (18), 1552 \200\2231558 . Slater, R., Cornelissen, L., Fabrizi, L., Patten, D., Yoxen, J., Worley, A., et al . (2010a ). Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomized c ontrolled trial. Lancet , 376 (9748), 1225 \200\2231232 . Fitzgerald, M. (2005). Th e development of nociceptive circuits. Nat Rev Neurosci , 6 (7), 507 \200\223520 . Fitzgerald, M. and Jennings, E. (1999). Th e postnatal development of spinal sensory processing. Proc Natl Acad Sci U S A, 96 (14), 7719 \200\2237722 . CHAPTER 8 central nociceptive pathways and descending modulation 81 van Praag, H. and Frenk, H. (1991). Th e development of stimulation- produced analgesia (SP A) in the rat. Brain Res Dev Brain Res , 64 , 71 \200\22376 . Willis, W. D. Jr, Zhang, X., Honda, C. N., and Giesler, G. J. Jr. (2002). A critical review of the role of the proposed VMpo nucleus in pain. J Pain , 3(2), 79 \200\22394. Slater, R., Fabrizi, L., Worley, A., Meek, J., Boyd, S., and Fitzgerald, M. (2010b). Premat ure infants display increased noxious-evoked neuronal activity in the brain compared to hea lthy age-matched term-born infants. Neuroimage , 52 (2), 583 \200\223589 . Th airu, B. K . (1971). Post-natal changes in the somaesthetic evoked potentials in the albino rat. Nat New Biol , 231 (18), 30 \200\22331 . Wollgarten-Hadamek, I., Hohmeister, J., Zohsel, K., Flor, H., and Hermann, C. (2011). Do sc hool-aged children with burn injuries during infancy show stress-induced activation of pain inhibitory mechanisms? Eur J Pain , 15 (4), 423.e1 \200\223e10 . Todd, A. J . (2010). Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci , 11 (12), 823 \200\223836 . Tolner, E. A., Sheik, A., Yukin, A. Y., Kaila, K., and Kanold, P. O . (2012). Subplate neur ons promote spindle bursts and thalamocortical patterning in the neonatal rat somatosensory cortex. J Neurosci , 32 (2), 692 \200\223702 . Tracey, I. and Johns, E. (2010). Th e pain matrix: reloaded or reborn as we image tonic pain using arterial spin labeling. Pain , 148 (3), 359 \200\223360 . Tracey, I. and Mantyh, P. W . (2007). Th e cerebral signature for pa in perception Zhang, Y. H., Wang, X. M., and Ennis, M. (2010). Eff ects of neonatal infl ammation on desc ending modulation from the rostroventromedial medulla. Brain Res Bull , 83 (1 \200\2232), 1 6 \200\22322 . Zohsel, K., Hohmeister, J., Flor, H., and Hermann, C . (2008). Altered pain processing in c hildren with migraine: an evoked potential study. Eur J Pain , 12 (8), 1090 \200\2231101 . and its modulation. Neuron , 55 (3), 377 \200\223391 . This page intentionally left blank SECTION 3 Social and psychological basis of pediatric pain This page intentionally left blank CHAPTER 9 Psychological theories and biopsychosocial models in pediatric pain Rebecca Pilla i Riddell , Nicole M. Racine, Kenneth D. Craig , and Lauren Campbell Summary Th e purpose of this chapter is to review existing biopsychosocial models of pediat ric pain and to examine common key factors across diff erent theoretical conceptualizations . Critical gaps in the empirical and theoretical literature are elucidated. In particular, lack of specifi c attention to developmental factors in biological, behavioral, and social functioning and the need for models that examine gaps in diff erent types of pain respondin g (e.g. immedi- ate acute pain response, acute pain responding in the context of chronic pa in) are highlighted. Moreover, the need for comprehen- sive, conceptual models, representat ive of current knowledge, that readily generate specifi c hypotheses confi rmable by experi menta- tion are also discussed as ways of moving the fi eld of pediatric pain forward, both conceptually and pragmatically. approximate an understanding of the complex enigma of another \200\231s pain. In addition t o comprehensiveness of bio-, psycho-, and social variables, ideally good models should repr esent current scientifi c knowledge in the fi eld and generate new ideas that can be subjec ted to empirical validation. Th is chapter will review key models in the fi eld and discuss their content in terms of comprehensiveness, rep- resentativeness, and potential for novel hypothesis generation. Th e \201 rst biopsychosocial model of pain: gate control theory A review of theoretical models would be incomplete without men- tioning the road the gate control theory of pain pa ved for modern transdisciplinary models of pain. Moving away from antiquated dualistic conc eptualizations of pain as existing in the mind or the body and building upon current knowle dge in the fi eld, Melzack and Wall (1965) proposed a groundbreaking model that included te stable mechanisms bridging the interplay between psychosocial and biological features of th e pain experience. One of the key land- mark implications of gate control theory and the su bsequent neuro- matrix theory for researchers and clinicians was the central role of the br ain in processing and representing noxious stimuli (Melzack, 1996, 1999). Ushering pain res earch into the modern age, the reali- zation that \200\230without the brain there would no t be pain \200\231 became a fundamental principle of pain research. Moreover, with recogni- tion that pain is substantially more than mere sensory experience, theoretical models broa dened their scope to include diverse factors implicated in pain experience, i.e. biological substrates, internal cognitive/aff ective/biological schema, social, and environmental (Cr aig et al., 1996). Despite minor criticisms that have been put forward including that pain inhibition is much more complicated than laid out in gate control, by recognizing the prima cy of the brain as the active recipient of noxious input and by specifying test- able mecha nisms that addressed both biological and psychosocial dimensions, these models set the stag e for research proliferation in the fi eld of pain that continues to this day. In addition, it also Introduction Except in very rare cases of congenital insensitivity, pain is inevi- table an d ubiquitous in the lives of children. Despite its universal- ity, the complexity of any ch ild or adult \200\231s actual experience of pain remains elusive to others, given its subje ctive nature. Nevertheless, the established deleterious impact of unmanaged pain during chi ld- hood on biological, psychological, and social well-being (Anand, 2000; Fitzgerald, 2005 ; Grunau, 2006; Hohmeister et al., 2010; Taddio et al., 1997) dictates a necessity to bette r understanding of not only the \200\230ever-elusive \200\231 pain experience but also how the more easily quantifi able \200\230pain expression \200\231 contributes to understandi ng the experience, assessment, and management of pediatric pain. Th e complexity of diff erent pain experiences (e.g. acute, acute- prolonged, chronic) and the varying importance of both broader system factors (medical staff , cultural norms) and more narrow sys- tem factors (such as parents and peers) have led to diverse frame- works i n understanding the interplay of biopsychosocial factors in pediatric pain. Having biopsych osocial models help scientists and clinicians attempt to discern and integrate the multifac eted pieces to SECTION 3 social and psychological basis of pediatric pain 86 fostered the development of more targeted biopsychosocial mod- els of pain. It was recently asserted that the prospects of advances in clinical assessment and management of children \200\231s pain are best served by comprehensive models that are inclusive of all determi- n ants (Hadjistavropoulos et al., 2011). While much social learning literature has focused on pediatric chronic pain, Page and Blanc hette argue that social learning theory is also a useful perspective from which to understa nd pediatric procedural pain (2009). For example, work by Chambers and col- leagues demonst rated that positive reinforcement and modeling of pain behaviors by parents during an acute pain task had an impact on child pain behavior, particularly for girls. Girls whose mother s demonstrated pain-promoting behaviors reported more pain than girls whose mothers did not react in the same manner (Chambers et al., 2002). Social learning theory is also relevant to pediatric procedural pain because of the roles anticipatory anxiety and avoid- ance play in pain responses (Page and Blanchette, 2009). Children may display anticipatory anxiety o r avoidance because they believe they will be unable to manage the procedure. Social learni ng theory is a useful model through which to understand the development and maintenance of child pain behavior in both acute and chronic pain contexts. As will become apparent, socia l learning contributes, either overtly or covertly, to the psychosocial foundation for all biopsychosocial models presented in this chapter. While not biopsychosocial in scope, two other theories should be discussed at the outset du e to their integral role in modern theories of pediatric pain. Both operant conditioning an d social learning models have set a foundation in which to help operationalize the psycholo gical and the social aspects for current biopsychosocial conceptualizations. Operant and social learning models of pediatric pain Operant models of pain have been exten sively used to under- stand chronic pain in the adult pain literature (Fordyce, 1976). Th e application to pediatric pain came onto the scene later. Turk and colleagues (1987) conduc ted one of the fi rst reviews on the involvement of the family on child chronic pain. Th ey discussed the concept of \200\230painful families \200\231, which are families where ther e is an increased incidence of chronic pain problems. Ultimately, they concluded that the f amily plays a major role as an agent of positive and negative reinforcement. Th e child \200\231s pain behaviors (e.g. cry- ing, moaning) can be strengthened or extinguished depen ding on environmental responses. Reinforcement may be particularly sali- ent for children w ith chronic pain since parent behaviors, such as attending to pain behaviors and granting p ermission to avoid daily activities, are related to higher levels of illness behaviors in c hildren with recurrent abdominal pain (Walker and Zeman, 1992). A more recent review has al so highlighted the contribution of operant conditioning on pediatric chronic pain and put f orward an integrative model (discussed fully later in this chapter) of factors impacting on pediatric chronic pain, including individual vari- ables such as parental reinforcement an d solicitousness (Palermo and Chambers, 2005). Th e current review found that biopsychosocial models of paedi- atric pain fell into two br oad categories: (1) a small and relatively recent literature specifi cally addressing chron ic pain and (2) a much more developed literature examining acute procedural pain. Th e foll owing examines these two broad categories, including a more detailed section on the social communication model (SCM) of pain as this model is one of the most widely cited explanatory models in the fi eld of pediatric pain. We begin our discussion of biopsycho- social model s by tackling pediatric chronic pain. Biopsychosocial models of pediatric chronic pain: theoretical beginnings Rather than defi n ing chronic pain in terms of duration, current conceptualizations base the distinction betw een chronic and acute pain on functionality (Woolf, 2010). Acute nociceptive pain serves to warn the organism of real or imminent tissue damage, whereas persistent pain diminishes or prevents movement and can pro- mote healing. Within the broad domain of persistent pain on e can identify chronic pain that is pathological because it serves neither function and wou ld appear to be the consequence of an abnormally functioning or damaged nervous system. Neu ropathic pain best illustrates the latter. A recent epidemiological review of chronic pain during childhood and adolescence described many diff erent types of chronic pain (e.g. head ache, back pain, musculoskeletal pain), with median reports of prevalence ranging between 1 1% and 38% of the populations studied (King et al., 2011). However, most of the studies rev iewed used \200\230duration of pain \200\231 to classify children \200\231s reports of pai n as chronic. A commentary on this review suggested that probably 5% to 15% of children suf f er from chronic pain that is disabling and requires professional intervention (von Baeyer , 2011). While reinforcement and punishment are key aspects to under- standing how pediatric pain re sponses develop and are maintained, by nature the theory tends to focus on more narrow cont ributors that are temporally linked to the pain response without expounding other aspects o f environmental learning such as through observa- tion and modeling. Social learning theory is a broader approach to learning emphasizing not only child factors related to their appr aisal of a painful situation but also familial/larger system infl uences on how to think ab out and act when in pain (Williams et al., 2011). Social learning theory puts forward that children learn within a social context, which is f acilitated by modeling and observa- tion (Bandura, 1977). According to social learning theo ry chil- dren learn behavior by observing others and imitating what they have observed. Mor eover, whether the behavior is imitated and learned depends on the salience of the model an d the consequence of the behavior. Th e child is also more likely to exhibit the learned be havior if he or she believes that the pain behavior will lead to a specifi c response from their support network (Osborne et al., 1989). An example of social learning was demonstrate d in a study that found that children of chronic low-back pain patients exhib- ited a highe r frequency of similar pain behaviors when they had a parent with a chronic pain condition versus when they had parents who were healthy or diabetic (Rickard, 1988). Clearly signifi cant numbers of children suff er from chronic pain, thus, models of this pa in type need to assist clinicians and research- ers in understanding why a subsample of chi ldren come to report disabling chronic pain when others do not. One must turn to for- mulat ions of how biological endowment and maturation interact with the physical and social envir onment to appreciate the emer- gence of individual diff erences in the experience and expre ssion of pain and disability. CHAPTER 9 psychological theories and biopsychosocial models in pediatric pain 87 Culture \200 Socioeconomic status \200 School environment \200 Social and peer intera ctions \200 Parental and family factors An integrative conceptual model for understanding pediatric chronic pain and disability Th ere have been recent attempts to describe interactions among biological, psychological, and social features and/or determinants of children \200\231s chronically painful conditions. In their \200\230integrative model of parent and family factors in pediatric chronic pain and associated disability \200\231, Palermo and Chambers (2005) focused on the psychosocial component of the biopsychosocial perspective. Th ey describe operant-behavioral perspectiv es of parent \200\223child inter- action within the broader framework of family systems the ories. Individual parenting variables, such as parenting style or parental reinforcement of child pain behaviors, are recognized as impor- tant within the context of dyadic interacti ons with the child. For example, the quality of the parent \200\223child interactions, whic h in turn are nested within broader family-level variables, such as family cohesion or over all functioning, were outlined. Specifi c child vari- ables, such as the level or nature of pain or disability, or moderat- ing/mediating variables, such as the child \200\231s gende r, age, emotional status, and coping, are hypothesized to infl uence the family, dyadic, an d individual variables. In this model, complex bidirectional rela- tionships are proposed b etween the aforementioned nested vari- ables and pediatric chronic pain, such that not only do parenting, dyadic, and family-level variables infl uence pediatric chronic pain, but pe diatric pain would have an impact on family dyadic inter- actions and overall functioning. Th is model emphasizes the devel- opmental context of these complex and bidirectional relat ionships and the dynamic, progressive nature of changes in relationships. Th us, there is a n emphasis on recognizing that the specifi c variables of interest would vary with the deve lopmental status of the child and contribute to developmentally appropriate care. Ultimatel y, the model emphasizes the mutually infl uencing relationship between the family unit \200 \231s functioning (both the whole system and multiple subsystems within) and the child \200 \231s pain, functional disability and the variables that moderate or mediate the relationsh ip between the two. In this model, psychosocial factors within the narrow family system are handled well because the model accurately refl ects cur- rent knowledge on this topic. Th is is clearly seen in the specifi cation of potential mediators/moderators that may infl ue nce the relation- ship between pain and functional disability. However, although not its se t out purpose, in terms of comprehensiveness, it does not go beyond immediate family factor s (such as medical systems and cultural norms) and does not look at the interplay with biol ogical factors within the child. Moreover, the actual relative relationships among individu al, parent, and family factors on chronic pain/func- tional disability are vague. Social Individual beliefs \200 Coping \200 Mood/a \200ect \200 Anxiety/fear vity vviittyy fs ffss iiee ie l ll ee e bb b hh h tt t e ee s ss uu u ee e cc c nn n aa a tt t b bb s t i b a h h t Psychological i ii tt t cc c aa a g gg nn n i ii kk k oo o mm m p pp ee e ee e l ll a aa cc c l ll l ll S SS a aa i ii s ss e ee S SS l u uu y yy a H HH S SS h hh Physical health \200 Pain modulation \200 Sex \200 Pubertal development e P PP H Biological Figure 9.1 Guiding conceptual model for understanding pediatric chronic pain and disability . Reproduced from Tonya M. Palermo, Cognitive-Behavioral Th erapy for Chronic Pain in Child ren and Adolescents , Oxford University Press, Inc., New York, USA, p. 13, Copyright 201 2, by permission of Oxford University Press. socioeconomic status, school environment, and characteristics of the health care system, we re recognized as providing context for the more proximal family and parent social factors. A novel aspect of this model is close examination of the role of health habits (such as sle ep, physical activity, substance use) play in pediatric chronic pain and disability. Explic itly making stable health habits salient highlights the importance of assessing these perip heral but fun- damental behaviors because of their potential role in moderating pain and di sability, particularly in older children and adolescents. Th is model posits bidirectional relationships among biological, psy- chological, and social factors with biological factors nested within the psychological context of the child, which in turn is nested within socia l contexts. Health habits would develop on the basis of the interplay of all three factors. Developmental considerations are advanced in this model, with the biology of pubertal deve lop- ment highlighted as particularly important. Refl ective of current research in the bro ader fi eld of pediatric psychology, the innova- tion of including health habits are noted as particularly relevant in adolescent populations. Th e model is broad in scope and descri bes an interplay of diff erent aspects of the systems. However, while the comprehensiveness and representativeness of the model facilitates a broad inventory of potential factors in chronic pain, this appears to come at the cost of its specifi c predictive power. Specifi c hypoth- eses about how factors within diff erent systems interact for empiri- cal validati on purposes (e.g. mood, culture, and puberty) and the directionality of these relationships are not readily evident from the model descriptions. Palermo (2012) extended the theoretical foundation proposed by Palermo and Chambers (2005) by explicitly adding in new com- ponents to the model, namely: (1) biological processes, (2 ) the dimension of psychological factors infl uencing health habits, and (3) social factors that go beyond consideration of parents and the family. Th e \200\230guiding conceptual m odel for understanding paediat- ric chronic pain and disability \200\231 (see Figure 9.1 ) is therefore more comprehensive in its scope. In terms of the biological levels of infl u- ence, consideration was given to ontogenetic maturation, includ- ing genetic factors, centr al nervous system functioning, sex, and pubertal status. Psychological variables proposed a s important in pediatric chronic pain include individual beliefs, coping, mood/ aff ect, an xiety, and fear. Broader social variables, such as culture, As discussed earlier, integrative models in the area of pediatric chronic pain are still in their early stages, with modeling typically representing the product of a particular inves tigative group. In con- trast, pediatric models of acute pain began proliferating about a d ecade earlier and have had the benefi t of diverse viewpoints on the topic. Th e following section addresses a number of recent models. Biopsychosocial models of pediatric acute pain Contrary to the dearth of theoretical litera ture on pediatric chronic pain, several models that specifi cally address acute or pro- ced ural pediatric pain have been advanced in the pediatric pain SECTION 3 social and psychological basis of pediatric pain 88 literature. In all of these models, the proposed relationships and interplay between variab les are presented in the context of a par- ticular painful episode (e.g. a specifi c immuni zation or other pain- ful medical procedure). among features and determinants of the pain experience choosing rather to specifi cally out lay the directionality of certain relation- ships. However, with this model we see a diff e rent type of limitation in that while specifi c mechanisms are readily identifi able and te st- able, potential gaps in the conceptualization of relationships between variables are ev ident. For example, whereas it is hypothesized that child factors (such as coping behaviors ) or parent factors (such as anxiety) can modulate the child \200\231s short-term pain resp onse or long- term distress memories, the model does not explicitly propose that the child \200\231s short-term pain response or long-term distress memories would exert infl uence on the child \200\231s coping behaviors or the parent \200\231s anxiety. Moreover, it provide s only a surface treatment of biological variables and a more comprehensive integration of biological factors would improve its conceptual value. A social-ecological framework for understanding procedure pain Informed and laid out simila rly to Bronfenbrenner \200\231s (1977) social- ecological framework, Kazak and Kunin-Batson \200\231s (2001) model sit- uated the child in pain at the center of a series of nested co ncentric circles representing the increasingly broad social settings that have an impact on a child in pain and that exert bidirectional infl uences on the child. Contained in the fi rst circle of infl uence, the microsys- tem, are child-specifi c, or intrapersonal, factor s such as age, biology, coping, health, and the pain experience itself. In the mesosystem, or second circle of infl uence, are social factors in the child \200\231s immedi- ate life contexts, such as those relating to family, peers, school staff , and hospital staff , and the interrelationships between these social units. Finally, broader social environments are represented by the largest circle of infl uence or the exosystem, such as social networks of parents, ethnocultural infl uences, including cultural beliefs and practices, health car e systems, and public policy. Th e interpersonal meso- and exosystems are hypothesized to e xert a direct and indi- rect impact on the child in pain (the microsystem) and all three sy stems are expected to interact, a position this perspective shares with other models discus sed. Once again, the model, while compre- hensive in its scope and grounded in current rese arch, has limited impact beyond providing a comprehensive description of potential variable s related to procedural pain. In essence, specifi c hypothesis testing of the dynamic inter play of nested spheres is impossible because of the large number of interactive possibiliti es that diff er- ent factors within diff erent spheres present. Young \200\231s model of pediatric procedural pain Similarly to Cohen \200\231s model, Youn g \200\231s (2005; see Figure 9.2 ) biopsy- chosocial model contextualizes pediatric proced ural acute pain by fi rst breaking the time sequence of a procedural pain event into three phases: (1) pre-procedure, (2) procedure, and (3) post- procedure. Th is framework acknowle dges that while acute pain occurs in a distinct episode of time (procedure), it is substant ially infl uenced by pre-procedural factors, such as the mindset the child brings to the pr ocedure (memories of past pain, fear/anxiety, tem- perament), unique biological disposition s (such as pain receptor density, endogenous opioids), and social infl uences (such as pare n- tal modeling, cultural beliefs, media attention, peer infl uences). Furthermore, the cum ulative impact of both pre-procedural and procedural factors would continue to infl uence t he child aft er the procedure has been completed. Similar observations must apply to acute pain arising from injury. Importantly, this model stands alone from models reviewed thus fa r by including a specifi c feedback loop postulating that aft er the procedural pain respon se, long-term eff ects of pain and distress (such as memories of the acutely painful experi ence) will in turn directly impact on an individual \200\231s cognitive control and coping skills in the next painful experience.