CHAPTER 5 prevention of the development and maintenance 43 Table 5.2 Reviews of predictors of pediatric pain (systematic and non-systematic) Pain condition Authors Outcome Findings (Gieteling et al., 2011) a Recurrent abdominal pain Persistence of RAP Predictors: prognostic factors, markers High levels of negative life events High levels of functional gastrointestinal complaints i n family Illness perception Female sex Behavioral disturbances Psychological disorders Seve re abdominal pain. Young age Low educational level Depressive/anxiety disorders Self-percei ved academic competence Long duration of abdominal pain History of two or more surgeries Pr esence of other associated symptoms (nausea, vomiting, headaches) High levels of functional disability Low socioeconomic status Attitude towards health care Non-signi \201 cant predictors, prognostic factors, markers: Unclear/still unknown: (Schar \200 , 1997) RAP Correlates, predictors, prognostic factors, markers: Underlying physiological predisposition Dietary in \202 uences Anxiety Recent stressful ev ents and coping abilities Family issues (Schulte et al., 2010) Development of RAP Predictors, prognostic factors, markers: Abdominal in \202 ammation processes Familiar genetic vulnerability to gastrointestinal sy mptoms and psychopathology Temperament Life events and stressors Psychopathological comorbi dity Maladaptation to RAP Predictors, prognostic factors, markers: Maladaptive pain processing Maladaptive pain communication in the family Maladaptive coping style Psychopathological comorbidity (Chogle and Saps, 2009) RAP Correlates, predictors, prognostic factors, markers: Stress, school-related stress Parent-related factors psychological factors Family demograph ics Seasonal variations Infectious agents Altered intestinal \202 ora Antibiotics Diet Recurrent pediatric headache (Martin and Smith, 1995) Recurrent pediatric headache Correlates, predictors, prognostic factors, markers: Depressive and symptoms Stress Multiple somatic symptoms Exposure to pain models Internaliz ing behaviors (+ externalizing behaviors for boys) (Continued) SECTION 1 introduction 44 Table 5.2 (Continued) Pain condition Authors Outcome Findings Musculoskeletal pain (Malleson et al., 2001) Predictors, prognostic factors, markers: Intrinsic factors: Low pain thresholds Female gender Hypermobility Poor perceived control o ver pain and maladaptive pain coping strategies Di \203 cult temperament Extrinsic factors : Previous pain experiences Social deprivation Physical or sexual abuse Parenting modeling of pain behaviors Sleep disturbance Exercise Development of musculoskeletal pain/ \201 bromyalgia and disability (Prins et al., 2008) a Development of the upper quadrant musculoskeletal pain Predictors, prognostic factors, markers: Static sitting posture Depression Stress Psychosomatic symptoms Gender Age a Systematic reviews. prevention and treatment approaches to childhood RAP, but they do not provide a comprehensi ve, multidisciplinary approach to the treatment of RAP nor do they provide insight into the eff ectiveness of combining, or the optimal combination of, various approaches. Methodolog ical challenges and realistic constraints and costs asso- ciated with conducting multidisci plinary, multiple group studies may, in part, explain this lack of integrative research. In vestigating the effi cacy of separate interventions is a good fi rst step in design- ing pr evention and treatment programs. But it is important to keep in mind that the outcome of su ch research results in isolated islands of knowledge and a lack of understanding of the opt imal multidisciplinary treatment combination that would be most eff ec- tive. Th e next ste p would be to conduct outcome research combin- ing multiple interventions consisting of tho se that have been shown to be the most eff ective. provide a better integration of research into clinical practice and focused specifi cally o n postoperative pain control, pain assess- ment, needle-related pain, and encouraging paren tal involve- ment in children \200\231s pain management. Th is type of model is essential t o knowledge translation and the implementation of systematic programs aimed at preventing a nd reducing acute pain in hospital. Two important areas targeted by this model are procedural pain and postoperative pain. Beca use the timing and nature of these procedures are known in advance, it is possible to condu ct lon- gitudinal studies beginning prior to the procedures in order to identify risk and p rotective factors associated with the acute pain experience. Systematic reviews of the literature on procedural pain have supported development of clini cal practices guidelines that outline effective pharmacological and non-pharmacological int erventions (including contextual, behavioral and cognitive strategies) to reduce procedural pain (e.g. Taddio et al., 2010) (see Table 5.3 ). Th e non-modifi able factors identifi ed earlier (e.g. age, sex) can help in identifying ch ildren at higher risk of developing pain and engage them in early prevention treatments. Mo st of the prognos- tic factors, predictors, and risk factors, however, are modifi able and intervention strategies should focus on minimizing the risk of developing pain or maintaini ng pain and pain-related disability associated with these factors. Research has also focused on reducing acute postoperative pain. One randomized controlled t rial on the effectiveness of behavioral interventions on post-operative pain in children sh owed that behavioral preparation reduces anxiety before surgery and during induction of ane sthesia, and leads to lower frequency of emergence delirium, lower consumption of anal- ges ic in the recovery room, and shorter stay in the recovery room (Kain et al., 2007). Guided imagery has also been found to reduce levels of pain and anxiety hours, but not 1 day after surgery when used 1 week and a few hours before surgery (Huth et al., 2004). Primary prevention of acute pain of iatrogenic origin Signifi cant eff orts have been deplo yed to prevent or reduce pain during hospitalization. A forerunner of this type of preventi on was the implementation of the \200\230ouchless place model \200\231 in the 1990s (Schec hter, 2008). Th e goals of this program were to CHAPTER 5 prevention of the development and maintenance 45 Table 5.3 Evidence-based interventions to reduce procedural-related pain (i.e. immunization and injection pain) in infants, children, and adolescents Systematic reviews evaluating the e \200 ect of these interventions Non-pharmacological management Infants Breastfeeding Kangaroo care (skin-to-skin contract) A sweet-testing solution Swaddling/faci litated tucking Rocking/holding Sucking-related interventions (Pillai Riddell et al., 2011; Stevens et al., 2010) (Cepeda et al., 2006; Chambers et al., 2009; Uman et al., 2006) Children and adolescents Psychological interventions: \227\206 Distraction (e.g. music, cartoon movies) \227\206 R elaxation breathing \227\206 Information/preparation \227\206 Combined cognitive-behavior al interventions Physical interventions/injection technique: \227\206 Injecting the least painful brand during vaccination \227\206 Having the child sit up \227\206 Stroking the s kin or applying pressure close to the injection site before and during injection; \227\206 Injecting the most painful vaccine last when 2 vaccines are being administered sequentially during a single o \203 ce visit; \227\206 Performing a rapid intramuscular injection without aspiration. Pharmacological interventions Topical anesthetics (e.g. EMLA \204 ) (Taddio et al., 2009) Primary prevention of chronic pain Very little is known about primary prevention of chronic pain mainly because most research is conducted when the pain is already present or chronic . One area that has received some empirical atten- tion involves perioperative pain. Interv ention strategies that aim to minimize acute postoperative pain intensity have the potentia l to play an important role in preventing the development of chronic post-operative pain. T h ese interventions include pharmacological and psychosocial approaches to minimizing pain. noxious preoperative, intraoperative, and/or postoperative stimuli. Th ese stimuli induce p eripheral and central sensitization, which increase postoperative pain intensity and analge sic requirements. Preventing sensitization reduces pain and analgesic requirements. Th e re ason why pre-emptive analgesic interventions have been equivocal is because the classic, tw o-group, pre- versus post-surgery design assumes that the intraoperative nociceptive barrag e contrib- utes to a greater extent to postoperative pain than does the post- operative noc iceptive barrage. However, some studies have since shown that central sensitization is indu ced to an equal (or greater) extent by incision and intraoperative trauma, on the one hand (i.e. in the post-surgical treatment group), and postoperative infl amma- tory inputs and/o r ectopic neural activity, on the other (i.e. in the preoperative treatment group), which w ould lead to non-signifi - cant intergroup diff erences in pain and analgesic consumption. Th e absence of signifi cant diff erences in postoperative pain or analgesic consumption be tween the groups may point to the relative effi cacy in reducing central sensitization of p ost incisional or postsurgical blockade, and not to the ineffi cacy of preoperative blockad e (Katz et al., 2011). Pre-emptive/preventive analgesia Pre-emptive analgesia involves blocking pre- or intraopera tive versus postoperative nociceptive inputs with the aim of prevent- ing a state of centra l sensitization; thereby leading to less intense postoperative pain and lower analgesic con sumption (Katz, 1995; Kissin, 2000). Preventive analgesia is a broader concept that aims to prevent the development of sensitization (peripheral and cen- tral) by blocking noxious in puts perioperatively (pre-, intra-, and postoperatively). Systematic reviews of the effi ca cy of pre-emptive analgesia are equivocal (Katz, 2003, Ong et al., 2005). Th e literature on pediatric pre-emptive/preventive analgesia (Yaster, 2010) is at best equ ivocal. Some studies have found that pre-emptive analgesia signifi cantly reduces postopera tive pain scores (Giannoni et al., 2001; Kundra et al., 1998) whereas similar studies fail to show a benefi t (Giannoni et al., 2002; Ozcengiz et al., 2001). In contrast, more recent reviews suggest that preventive analgesia is more eff ective than the more narrow, classical view of pre-emp- tive analgesia in large part due to the blockad e of nociceptive inputs across the perioperative phases of surgery (Katz and McCartney, 200 2; Katz et al., 2011) and the use of more eff ective agents such as the alpha 2 delta ligan ds (Clarke et al., 2012).Th e focus of preven- tive analgesia is not on the relative timing of analgesic or anaes- thetic interventions as is pre-emptive analgesia, but on attenuatin g the impact of the peripheral nociceptive barrage associated with Psychosocial interventions Researchers have examined the eff ectiveness of interventions ai med at reducing psychological distress and/or pain intensity during the SECTION 1 introduction 46 perioperative period. In a randomized controlled trial of cognitive behavioral therapy (inf ormation, coping skills training, combined information and coping skills training, or contr ol group) adminis- tered once before and once aft er surgery, the combined interven- tion g roup showed reduced levels of pre- and post-surgical anxiety, whereas the coping skills gro up showed signifi cantly reduced lev- els of postoperative anxiety and pain intensity (LaMo ntagne et al., 2003). As well, the control group exhibited the highest levels of postoperat ive pain 4 days aft er surgery compared to the treatment groups. Finally, the information-o nly group signifi cantly increased their level of usual activities at 6 versus 3 months aft er surgery whereas younger children in the control or combined groups were more engaged in social activities compared to children in the coping group (LaMontagne et al., 2004). Simi larly, a randomized controlled trial examining the eff ectiveness of behavioral inter- vent ions (family-centered behavioral preparation versus parental presence at induction versus o ral midazolam versus control) found that children who received family-centered behavioral p reparation before surgery exhibited lower preoperative anxiety, had a lower frequency of em ergence delirium, consumed less analgesic in the recovery room, and were discharged faster from the recovery room compared to children in the other groups (Kain et al., 2007). Recent adult chronic pain research indicates that the risk and protective factors involved in the transition to chronicity diff er from those involved in the maintenance of already e stablished chronic pain (Katz, 2012). For example, a prospective, longitudinal study of pat ients aft er lateral thoracotomy, showed that perioperative factors (i.e. preoperative pain disability, preoperative emotional numbing symptoms, and acute postoperative pain intensit y) failed to predict the transition to chronic pain disability 6 months aft er surgery, but the very same variables measured 6 months later were highly sig- nifi cant predictors of t he maintenance of 12-month chronic pain disability (Katz et al., 2009). Seebach et al. (201 2) reported a simi- lar pattern of fi ndings in their prospective, longitudinal study of th e psychosocial recovery trajectory in patients aft er spine surgery. Th e results indicate the risk factors that predict the maintenance of established chronic postsurgical pain disa bility or pain intensity, pain interference, and functional status are diff erent from thos e that predict the initial transition to chronicity. Evidence for the distinction between t riggering and maintaining factors in paedi- atric chronic post-surgical pain has been provi ded by Pag et al. (2013) who showed that pain unpleasantness ratings 24 to 48 hours aft er surgery predicted the transition to moderate/severe CPSP at 6 months (but not 12 months) , whereas 6-month anxiety sensitiv- ity scores predicted the maintenance of moderate/severe CPSP (i.e. from 6 to 12 months aft er surgery). Implications of these fi ndings for the de sign and conduct of pediatric studies and for pain pre- vention are discussed in the follow ing section. Secondary and tertiary prevention of chronic pain Psychological interventions including cog nitive behavioral treat- ment, biofeedback, and/or relaxation can be eff ective in managing a wide array of pain problems, whereas pharmacological interven- tions appear to be more p ain-condition specifi c. A Cochrane review has shown that psychological treatments are eff ective at reducing pain, but not disability, in children with headaches, fi bromyalgia, and recurrent abdominal pain (Eccleston et al., 2009). A review of complementary and alternati ve medicine approaches has reported that children with recurrent headaches benefi t signifi cantly from hypnosis and guided imagery whereas other approaches, such as acupuncture, mas sage therapy, homeopathy, biofeedback, arts, and herbal therapy were found to be \200\230p ossibly effi cacious \200\231 or \200\230promising \200\231 for other pediatric chronic pa ins (Tsao and Zeltzer, 2005). Future research directions and clinical implications Th e fi eld of pediatric pain preventi on, particularly chronic pain, is in its infancy. Th e search for risk and protective facto rs would be aided by well-designed, prospective, longitudinal epidemiologi- cal studies. Th ese studies would: (1) assess participants prior to the onset of the procedure or as early as possible aft er injury or illness, (2) follow them until chronic pain has developed (i. e. 3 \200\2236 months), and (3) include a suffi cient number of follow-ups to capture the c ritical window during which relevant processes and factors con- tribute to the transition t o chronicity. It is crucial to assess outcomes at multiple time points because the transiti on to chronic pain and related psychosocial dysfunction is a dynamic process that evolves o ver time (Katz, 2012; Katz and Seltzer, 2009; Kehlet and Rathmell, 2010). One area of tertiary prevention that has received signifi cant attention is headache. Chron ic daily headaches and migraines are among the most frequent pediatric pain conditions. Rev iews of pharmacological interventions show that acetaminophen, ibupro- fen, and a sumatript an nasal spray (Damen et al., 2005) as well as propranolol and fl unarizine (Victor and Rya n, 2003) signifi cantly reduce pediatric migraine-related symptoms. More high-qual- ity ran domized control trials are needed to establish the eff ect of additional drugs for which no trials of suffi cient quality have been conducted (Damen et al., 2005; Victor and Ryan, 20 03) in addi- tion to examining the long-term potential of these drugs in pre- venting pain and related disability. Moreover, reviews have found that psychological therapies (Cvengros et al., 2007; Kroner-Herwig, 2011) are eff ective in treating pediatric headaches, but thi s eff ect was moderated by other variables, such as demographic and treat- ment characteris tics. Such research would build on current observational studies of individual factors associated with the pain experience. Th is will lead to the development of integrative theoretical mo dels of pain and disability adapted to pediatric populations, to a better under- standing o f the risk and protective factors involved in the transition of acute to chronic pain, and ultimately to clearer guidelines and recommendations for chronic pain prevention. Current research on factors associated with the presence of chronic pain in children and me chanisms associated with the tran- sition from acute to chronic pain can help further our u nderstand- ing of the physical, pharmacological, and psychosocial correlates of pediatric c hronic pain and provide important information for tertiary pain prevention. Prospective stu dies of the development of chronic pain and the transition from acute to chronic pain will help identify important risk factors, which can lead to the development of primary and seco ndary prevention strategies. Together, these results suggest that psychological and pharmaco- logical factors play an im portant role in the secondary and tertiary prevention of chronic pain. More research is nee ded to examine the long-term benefi ts of using these interventions. CHAPTER 5 prevention of the development and maintenance 47 In addition, few randomized controlled trials have examined the eff ectiveness of psycholog ical treatments in the treatment of pae- diatric chronic pain and disability and little is known about recent intervention strategies (e.g. acceptance and commitment therapy; Wicksel l et al., 2009) that successfully reduce pain-related disabil- ity. Systematic reviews show psychological treatment is eff ective for pain, but little evidence to support an eff ect on pain disability. Clinical trials are needed to extend the support of psychological treat ment for pain to pain-related disability and other pain-related outcomes. Clarke, H., Bonin, R. P., Orser, B. 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