Cystic \201 brosis Cystic fi brosis (CF) is an inherited multisystem disorder, and the pr imary defect relates to dysfunction of the cystic fi brosis trans- membrane conductance reg ulator protein (CFTR). CF is character- ized by obstruction and infection of airways and by maldigestion and its consequences. As a result, CF is the major cause of severe chronic lu ng disease in children, and of most cases of exocrine pan- creatic insuffi ciency in early life (Egan, 2011 ). Due to the wide array of presenting symptoms and complications, CF ente rs the diff eren- tial diagnosis of many pediatric conditions (Egan, 2011 ). CF is the most common life-limiting recessive genetic trait among white peo- ple, with a prevalence of ap proximately 1/3500 live births in north- ern Europe, North America, and Australia and New Z ealand. Th e prognosis for children living with CF has improved dramatically over the last few decades. Th is is due to several factors including improved nutrition and improved trea tment of respiratory infec- tions. Notwithstanding this improvement in prognosis, this illn ess is still associated with signifi cant morbidity, but there has been little evaluation o f the extent and impact of pain on children with CF. Special considerations for pharmacotherapy in HIV/AIDS Excessive activation of the N-methyl -D-aspartate (NMDA) recep- tor occurs in the presence of gp120, a protein found on the oute r envelope of HIV (AIDSinfo, 2008 ). It is thought that this may con- tribute to increased pain severity potentially requiring escalating opioid and sedative requirements. Both dextr omethorphan and ketamine block the NMDA receptor, but their use can be limited by an unfavo rable side eff ect profi le. Ketamine has anecdotally been associated with severe cardiac r hythm disturbance, electrolyte abnormalities, and even cardiac arrest in children with adva nced HIV and AIDS (AIDSinfo, 2008 ). Adult literature suggests that methadone administratio n may be associated with lower CD4 cell count and CD4/CD8 cell ratios and in vitro studies also suggest an increase in HIV replication in human blood monocyte-derived macrophages exp osed to methadone (AIDSinfo, 2008 ). Pain in cystic \201 brosis Recognition that pain is a common symptom in children with CF was fi rst established in the 1990s. A retrospective chart review at a tertiary care hospit al was conducted summarizing the end-of-life care of US patients more than 5 years of age a nd dying from CF (Robinson et al., 1997 ). Twenty-fi ve per cent of these patients had been receiving opioids for the treatment of chronic headache and/ or chest pain for more than t heir last 3 months of life. When opio- ids were used for the treatment of breathlessness an d/or chest pain, the proportion increased to 86%. When pain was present, it was described a s \200\230serious \200\231 pain with chest, head, extremity, abdomen, and back being the m ore common locations. Myopathic pain is managed by fi rstly addressing the underlying cause, decreasing infl amma tion, and maximizing ART. Neuropathic pain and peripheral neuropathy due to medication is m anaged by stopping medications that produce neuropathy, and using analgesics as per the WHO recommendations (WHO, 2012 ). Neuropathic pain may also be managed with -aminobutyric a cid agonists (GABA) such as baclofen, ART, NMDA receptor blockade, and anticonvulsants (AID Sinfo, 2008 ). Abdominal pain from infl ammatory processes such as pancreatitis, infection, gall bladder and biliary tract disease, mal- absorption syndromes, tumors, and medication side eff ects can all cause persisting pain in children with HIV/AIDS. Mouth pain from apht hous ulcers and dysphagia are managed by using mouth washes, a soft brush, having soft food , and appropriate analgesia. Candidiasis should be treated with antifungals such as miconaz ole, fl uconazole, and topical anesthetics for local pain relief. Aphthous ulcers have also been managed with prednisolone and dexamethasone mouth washes. Th e incidence of chronic pain in children with CF increases sharply in the last 6 months o f life (Ravilly et al., 1996 ). Headaches (55% of patients) and chest pain (65%) were frequ ently reported, although back pain (19%), abdominal pain (19%), and limb pain SECTION 4 pain in specific populations and diseases 324 (16%) were also common. In patients with headache, the main aeti- ologies were hypercarbia or hypoxia, migraine, and sinusitis. Th e majority of chest pain was musculoskeletal, with pleuritis, pneu- mothorax, and rib fracture also reported. and neurofi bromatosis 2 (NF2; Sahin, 2011 ). NF1 is more com- mon and has a better prognos is with a lower incidence of CNS tumors than NF2, but may still be associated with signifi cant morbidity. A recent comparative study of children and adults with CF exam- ined the prevalence of pain in CF and the consequences to activities of daily living (Sermet-Gaudelus et al., 2009 ). Th e study included 73 children (1 \200\22318 years) and 110 adults (18 \200\22352 years); 59% of the children and 89% of the adults reported at least one episode of pain during the previous month. Pain was signifi cantly more intense and lasted signifi cantly longer among adults, but incidence did not dif- fer signifi cantly between the two populations, and was not related to the severity of CF. In this study the most prevalent locations were the abd omen for children, and the back, head, and chest for adults. Although pain signifi cantly l imited physical activity, only 15% of patients reported that it caused absenteeism, and 27% reported that it negatively aff ected their family life. Th e mean intensity of great- est pain during the past month, rated on a 0 to 10 visual analog scale was 4.9 (2) (mean [stan dard deviation)) for children and 6 (2) for adults. Only 40% and 50%, respectively, of thos e with pain reported the use of analgesic treatment, mainly paracetamol. At least one episo de of procedural pain during the previous month was reported by 85% of children and 78% of adults. Th is study dem- onstrates the high incidence of undertreated pain in CF patients t hroughout their lives and indicates the need for a thorough assess- ment of pain in childre n with CF. Pain in neuro \201 bromatosis Neurofi bromas typically involve the skin, but may also be s ituated along peripheral nerves and blood vessels or within viscera, and can produce pain i n children (Sahin, 2011 ). Th e lesions characteristically appear during adolescence as sma ll rubbery lesions with a slight dis- colouration of the overlying skin. Neurofi bromas may be associated with swelling and local pain ( \200\230pins and needles \200\231 or \200 \230shooting \200\231 pain) and dysaesthesia in the nerve distribution. Plexiform neurofi b ro- mas are oft en present at birth and frequently located in the orbital or temporal regio n of the face, result from diff use thickening of nerve trunks (Sahin, 2011 ). Plexiform ne urofi bromas may produce overgrowth of an extremity and the deformity of the corresponding bone may cause pain. A neurofi broma occasionally diff erentiates into a malignant nerve cell tumor and the inci dence of phaeochromocytoma, rhab- domyosarcoma, leukemia, and Wilms \200\231 tumor is highe r than the general population (Sahin, 2011 ). Th e possibility of a malignant change in a n eurofi broma should be considered in the patient with pain which is persisting despite anal gesic treatment. Scoliosis is a common complication found in 10% of patients with neurofi bromatosis (Sahin, 2011 ), and this skeletal abnormality may also be a source of pain. In addition, pathologi cal fracture is occa- sionally associated with pseudoarthrosis, and should be considered in this setting if pain is of sudden onset, severe, and persisting. Reported interventions for pain in CF have included a variety of non-pharmacological and ph armacological therapies (Ravilly et al., 1996 ). Forty-one patients (53%) had pain severe e nough to require opioid treatment, and ten patients (13%) received opioids for more than 3 months. In eight patients with more severe pain, regional analgesia was found to be particu larly eff ective (Ravilly et al., 1996 ). Case example: neuro \201 bromatosis A 16-year-old boy presented to the pediatric pain clinic with neurofi bromatosis which was diagnosed at the age of 10 years. He presented with intermittent \200\230sharp, shooting \200\231 pain in his arm and this followed a C5, C6 nerve distribution. His imaging studies demonstrated multiple neurofi bromas along C5 and C6 nerves, but none suggestive of malign ant change. Initially well control- led on a combination of simple analgesics and gabapenti n as a treatment for neuropathic pain, his pain escalated over several months to become sev ere, constant, and precluded sleep. Th is change necessitated an increase in his analgesia to include an opi- oid given on a regular basis and the continuation of the gabapen- tin. A nerve biopsy was performed which diagnosed a peripheral nerve sheath tumor. Despite treatm ent with chemotherapy, the tumor progressed in size and caused further pain necessitat- ing the parenteral administration of an opioid and referral for palliative care. Case example: cystic \201 brosis A 14-year-old adolescent with CF was admitted to hospital with severe left -sided chest pai n exacerbated by deep inspiration. A chest X-ray revealed a fracture of the right anterior seventh rib and associated osteopenia. Th e patient was admitted to hospital for analgesia and chest physiotherapy. Analgesia consisted of intrave- nous opioid analgesia self-adminis tered via a patient-controlled analgesia (PCA) pump through a central venous access device. Th e young patient was encouraged to administer the opioid prior to chest physiotherapy an d instructed to support his chest wall when coughing. A TENS unit was used and gave improve d analgesia. Osteoclast inhibitor therapy was commenced, following endocrinology review, to correct the osteopenia and reduce the chance of spontaneous fracture in the future. Th is patient was discharged home 2 weeks later with a regular schedule of oral analgesia for man agement of his persisting pain. Neuromuscular diseases Neuromuscular diseases are disorders of the motor unit, which consis ts of the motor neuron, its axon, the neuromuscular junction, and the muscle fi bres innerv ated by the motor neuron. Pediatric neuromuscular conditions that may be associated with pa in include: developmental disorders of muscle (e.g. nemaline and central core disease), mus cular dystrophies (e.g. Duchenne \200\231s), spinal muscular atrophies, and Guillain \200 \223Barr syndrome (GBS). Neuro \201 bromatoses Nerofi bromatoses are autosomal dominant disorders that that cause t umors to grow on nerves and are associated with other abnormalities such as skin changes an d bone deformities. Th ere are specifi c diagnostic criteria for neurofi bromatosis type 1 (NF1) CHAPTER 32 persisting pain in childhood medical illness 325 Pain in neuromuscular disorders Although the neuromuscular diseases of childhood are a hete roge- neous group of conditions, there is oft en a similarity in the causa- tion of pain. M uscle weakness is common and sometimes associated with cramps, which can be distressing and for which simple reme- dies, such as massage, seem to be the most eff ective. Most persist ing pain in neuromuscular disease is a consequence of the orthopedic complications of muscl e weakness. In particular, pain associated with hip dislocation and progressive scoliosis. Pain can initially be mild in these orthopedic conditions and simple analgesics suf- fi cie nt for treatment. With progression, surgical options are oft en considered and may be more eff ective for pain relief in the longer term. Occasionally, a few young patients with neur omuscular con- ditions may require surgery to correct scoliosis or hip dislocation causing severe pain. If surgical options are precluded due to anaes- thetic risk, long-term opioid therapy for the management of severe pain may be warranted. described in children with GBS (Morris et al., 2003 ), the epidemiol- ogy of pain experienc ed by children with GBS is less well described and the literature is confi ned to the occas ional case report (Pier et al., 2010 ). Th e pathophysiology of pain in GBS is poorly understood. Putative mechanisms include irrit ation of the nervi nervorum innervating nerve trunks and the dorsal rami, demyelinating of large sensory nerve fi bres causing pain dysaesthesiae, and dysfunc- tion of small nerve fi bres. Animal studies have suggested a role for T-cell-medicated infl ammation and the rele ase of pro-infl ammatory cytokines producing thermal hyperalgesia and allodynia (Gorson, 20 10 ). Musculoskeletal pain related to prolonged immobility may also be a contributing facto r (Gorson, 2010 ). Case example: Guillain \200\223Barr A 10-year-old boy was transferred from a regional hospital to a tertiary children \200\231s hospital with a history of weakness in his hands and feet and a complaint of an uncomforta ble \200\230burning \200\231 sensa- tion in his hands and feet. Th e weakness progressed i n his limbs proximally and a diagnosis of GBS was made. Concern about progressive respirato ry muscle weakness necessitated admission to the pediatric intensive care unit for close mo nitoring of his respiratory status, but invasive ventilation was avoided and he was dischar ged from intensive care within 7 days. In the ward he complained of increasing pain related to the dysaesthesiae in his limbs, which was not responsive to simple analgesics. Given th e neuropathic quality of his pain he was administered gabapentin. Within 1 week of starting this medication his pain decreased and this greatly facilitated his rehabilitation program . Case example: neuromuscular diseases A 16-year-old boy with Duchenne \200\231s muscular dystrophy and severe persisting back pai n due to severe scoliosis was reviewed in a pain clinic for children. Corrective surgery wa s scheduled; however, severe and persisting pain necessitated the administra- tion of a reg ular schedule of opioid medication. Prior to starting the opioid he was reviewed by his res piratory team as he was being treated with nocturnal non-invasive ventilation for the treat - ment of hypercapnia. Th e respiratory team repeated a sleep study which demonstrated the eff ectiveness of his non-invasive ventila- tion. Th e opioid therapy was eff ective and wa s commenced under close supervision in hospital. His surgery was completed a few days later and initially he was closely monitored in the pediatric intensive care unit. His postopera tive analgesia accounted for the fact that he was needing opioid prior to surgery. His cour se was uneventful and at the time of discharge simple analgesics were only required for ade quate pain control. Cerebral palsy Cerebral palsy (CP) is a diagnostic term to describe a group of permanent, b ut non-progressive, disorders of movement and pos- ture causing activity limitation. CP may be attributed to a range of disturbances in the developing fetal or infant brain, for exam - ple, genetic, metabolic, ischaemic, and infectious causes (Johnston, 2011 ). Th e motor d isorders are oft en accompanied by disturbances of communication, sensation, perception, co gnition, and behav- iour, in addition to epilepsy and secondary musculoskeletal prob- lems (Johnston, 2011 ). Guillain \200\223Barr syndrome GBS is an acute immune-mediated polyradiculoneuropathy co m- prising a broad spectrum of clinical variants (Ruts et al., 2010 ). It oft en occurs fol lowing a non-specifi c viral infection and usually results in an ascending paralysis. In de veloped countries it is the most common cause of fl accid paralysis in children (47%), foll owed by transverse myelitis (19%), and then a variety of causes, includ- ing encephalomyeli tis, tick-bite paralysis, and infantile botulism (Morris et al., 2003 ). Pain in cerebral palsy Pain in children with CP is common (Engel et al., 2005 ) and is asso ciated with a lower quality of life and self-perception (Russo et al., 2008 ). Th erefore, clinicians should enquire about pain in every child with CP and consider appropriate pain m anagement (Riquelme et al., 2011 ). A recent cross-sectional multicentre European study det ermined the prevalence and associations of self-reported and parent-reported pain in childr en with CP of all severities (Parkinson et al., 2010 ). Children aged 8 to 12 years were ra ndomly selected from population-based registers of children with CP in eight European regio ns and a further region recruited 75 children from multiple sources. Data on pain in the we eks prior to the survey were available from 490 children who gave self-report and parents o f 806 children (who could not self-report) gave their Pain in Guillain \200\223Barr syndrome Data from a prospective study in adult patients w ith GBS indi- cated one-third had pain in the 2 weeks prior to the onset of weak- ness, two thirds had pain in the acute phase, and 38% overall had persisting pain at 12 months \200 \231 follow-up (Ruts et al., 2010 ). Low back and proximal muscle pain, radicular limb pain , peripheral dysaesthesiae, and arthralgias are common in adults; and multiple pain pattern s may coexist and overlap, which complicates clinical assessment (Gorson, 2010 ). Whilst pa raesthesiae are commonly SECTION 4 pain in specific populations and diseases 326 perception of their child \200\231s pain. Th e estimated population preva- lence of self-re ported pain in the previous week was 60% (95% confi dence interval (CI): 54 \200\22365%) an d that of parent-reported pain in the previous 4 weeks was 73% (95% CI: 69 \200\22376%). Ol der chil- dren reported more pain, but pain was not signifi cantly associated with severity of impairment. In parental reports, severity of child impairment, seizures, and parental u nemployment were associated with more frequent and severe pain. HIV prevention . [Online]. < http://www.womenchildrenhiv.org/ wchiv?page=wx-resource&root=t yp&cat=05%subcat=prrv&rid=2103 9 > (accessed 21 January 2009). Araujo , A. P. , Nascimento , O. J. , and Garcia , O. S. ( 2000 ). Distal sensory polyneuro pathy in a cohort of HIV-infected children over fi ve years of age . Pediatrics , 106 , E35 . Bajelidze , G. , Belthur , M. V. , Littleton , A. G. , Dabney , K. W. , and Miller , F. ( 2 008 ). Diagnostic evaluation using whole-body technetium bone scan in children with cerebra l palsy and pain . J Pediatr Orthop , 28 , 112 \200\223117. Berg , K. M. , Cooperman , N. A. , Newville , H. , and Arnsten , J. H. ( 2009 ). Self- effi cacy and depression as mediat ors of the relationship between pain and antiretroviral adherence . AIDS Care , 21 , 244 \200\223248. Th ere are many causes of pain in children with cerebral palsy, which can be categorized as: \231 Gastrointestinal (e.g. dysphagia, gastro-oesophageal refl ux, Brinley , F. J. Jr. , Pardo , C. A. , and Verma , A. ( 2001 ). Human immunodefi ciency viru s and the peripheral nervous system workshop . Arch Neurol , 58 , 1561 \200\2231566. constipation). \231 Orthopedic (e.g. hip subluxation and dislocation, equinus valgus deformities of knee and ankle, scoliosis, kyphosis, contractures). De Baets , A. J. , Bulterys , M. , Abrams , E. J. , Kankassa , C. , and Pazvakavambwa , I. E. ( 2007 ). Care and treatment of HIV-infected children in Africa: issues and challenges a t the district hospital level . Pediatr Infect Dis J , 26 , 163 \200\223173. \231 Neuromuscular (e.g. pain related to spasticity, nerve entrapments). Dobalian , A. , Tsao , J. C. , and Duncan , R. P. ( 2004 ). Pain and the use of outpatient services among persons with HIV: results from a nationally representative survey . Med Care , 42 , 129 \200\223138. \231 Rehabilitative (e.g. pain related to the physical therapy activities of stretching and bracing). Egan , M. ( 2011 ). Cystic fi brosis . In R. M. Kleigman , B. F. Stanton , N. F. Schor , J. W. St. Geme , and R. E. Behrman (eds) Nelson textbook of pediatrics , pp. 1481 \200\22314 96. Philadelphia, PA : Saunders . Pain treatment strategies should be directed at the specifi c causes listed and if analgesi c agents are needed, the general principles out- lined at the beginning of this chapter are applicable. Th e diagnos- tic process may be diffi cult, and a case has been made to obtai n a whole-body technetium bone scan in children with CP for whom there is no obvious case, as occasionally occult fractures may be identifi ed (Bajelidze et al., 2008 ). Novel treatm ents for pain related to spasticity include botulinum toxin type A injections (Lundy et al. , 2009 ) and intrathecal baclofen (Hoving et al., 2009a , 2009b ). Engel , J. M. , Petrina , T. J. , Dudgeon , B. J. , and McKearnan , K. A. ( 2005 ). Cerebra l palsy and chronic pain: a descriptive study of children and adolescents . Phys Occup Th e r Pediatr , 25 , 73 \200\22384. Epstein , L. G. , Sharer , L. R. , Oleske , J. M. , Connor , E. M. , Goudsmit , J. , Bagdon , L. , et al . ( 1986 ). Neurologic manifestations of human immunodefi ciency virus infect ion in children . Pediatrics , 78 , 678 \200\223687. Floeter , M. K. , Civitello , L. A. , Everett , C. R. , Dambrosia , J. , and Luciano , C. A . ( 1997 ). Peripheral neuropathy in children with HIV infection . Neurology , 49 , 207 \200\223212. Case example: cerebral palsy Fortuny , C. , Noguera , A. , Alsina , L. , Villaronga , M. , Vidal-Sicart , S. , and Sanch ez , E. ( 2008 ). Long-term use of bisphosphonates in the treatment of HIV-related bone pai n in perinatally infected pediatric patients . AIDS , 22 , 1888 \200\2231890. A 12-year-old girl with severe CP presented to the ED with behaviors indicating to her care -givers that she had severe pain. Normally a happy child she had a 48 h history of inconsol able crying and grimacing facial expressions. Previously diagnosed comorbidity included gas tro-oesophageal refl ux which was being treated with a proton pump inhibitor and subluxed h ips for which surgery was not intended in the near future. Apart from demonstrating signs c onsistent with severe CP her clini- cal examination revealed severe hip adductor muscle spa sm. Th e centrally acting muscle relaxant baclofen was administered regularly and her pain behaviors improved dramatically. Gaughan , D. M. , Hughes , M. D. , Seage , G. R. 3rd , Selwyn , P. A. , Carey , V. J. , Gor tmaker , S. L. , et al . ( 2002 ). Th e prevalence of pain in pediatric human immunodefi ci ency virus/acquired immunodefi ciency syndrome as reported by participants in the Pediatric Late Outcomes Study (PACTG 219) . Pediatrics , 109 , 1144 \200\2231152. Gorson , K. C. ( 2010 ). Th is disorder has some nerve: chronic pain in Guillain- Barre syndrome . Neurology , 75 , 1406 \200\2231407. Gray , G. E. , Laher , F. , and Lazarus , E. ( 2010 ). Th e management of pain in adults an d children living with HIV/AIDS. In A. Kopf and N. B. Patel (eds) Guide to pain management in low-resource settings . IASP. [Online]. Available at: < http://www.iasp-pain.org/AM/ Tem plate.cfm?Section=Home&SECTION=Home, Home, Home, Home&CONTENTID=11669&TEMPLATE=/CM/HTMLDisp lay.cfm > (accessed 12 January 2012). References AIDSinfo. ( 2008 ). Managing complications of HIV infection in HIV infected chil dren on antiretroviral therapy. Guidelines for the use of antiretroviral agents in pediatri c HIV infection [Online]. Available at: < http//www. aidsinfo.nih.gov >. Gumbo , T. , Kadzirange , G. , Mielke , J. , Gangaidzo , I. T. , and Hakim , J. G. ( 2002 ) . Cryptococcus neoformans meningoencephalitis in African children with acquired immunodefi ciency syndrome . Pediatr Infect Dis J , 21 , 54 \200\22356. Hewitt , D. J. , McDonald , M . , Portenoy , R. K. , Rosenfeld , B. , Passik , S. , and Breitbart , W. ( 1997 ). Pain syn dromes and etiologies in ambulatory AIDS patients . Pain , 70 , 117 \200\223123. AIDSinfo. ( 2011 ). Panel on antiretroviral therapy and medical management of HIV-infected children. Guidelines for the use of antiretroviral agents in pediatric HIV infection [Onlin e]. Available at: < http://aidsinfo.nih.gov/ ContentFiles/PediatricGuidelines.pdf >. Hirschfeld , S. , Moss , H. , Dragisic , K. , Smith , W. , and Pizzo , P. A. ( 1996 ). Pain in pediatric human immunodefi ciency virus infection: incidence and characteristics in a s ingle-institution pilot study . Pediatrics , 98 , 449 \200\223452. Hoving , M. A. , Van Ra ak , E. P. , Spincemaille , G. H. , Palmans , L. J. , Becher , J. G. , and Vles , J. S. ( 2 009 a). Effi cacy of intrathecal baclofen therapy in children with intractable spastic cere bral palsy: a randomized controlled trial . Eur J Paediatr Neurol , 13 , 240 \200\223246. Amery , J. , Meiring , M. , Albertyn , R. , and Jassal , S. ( 2009 ). Pain . In J. Amery , (ed.) Children \200\231s palliative care in Africa , pp. 97 \200\223124. Oxford : Oxford U niversity Press . Ammann , A. ( 2009 ). Antiretroviral drug dosing for infants and children: calculation by w eight or body surface area, global strategies for CHAPTER 32 persisting pain in childhood medical illness 327 Russo , R. N. , Miller , M. D. , Haan , E. , Cameron , I. D. , and Crotty , M. ( 2008 ). Pa in characteristics and their association with quality of life and self-concept in children with hemiplegic cerebral palsy identifi ed from a population register . Clin J Pain , 24 , 335 \200\223342. Hoving , M. A. , Van Raak , E. P. , Spincemaille , G. H. , Van Kranen-Mastenbroek , V. H. , Van Kleef , M. , Gorter , J. W. , et al . ( 2009 b). Safety and one-year effi cacy of intr athecal baclofen therapy in children with intractable spastic cerebral palsy . Eur J Paedia tr Neurol , 13 , 247 \200\223256. Ruts , L. , Drenthen , J. , Jongen , J. L. , Hop , W. C. , Visser , G. H. , Jacobs , B. C. , et al . ( 2010 ). Pain in Guillain \200\223Barre syndrome: a long-term follow-up study . Neurology , 75 , 1439 \200\2231447. Hulgan , T. , Haas , D. W. , Haines , J. L. , Ritchie , M. D. , Robbins , G. K. , Shafer , R. W. , et al . ( 2005 ). Mitochondrial haplogroups and peripheral neuropathy during antire troviral therapy: an adult AIDS clinical trials group study . AIDS , 19 , 1341 \200\223134 9. Sahin , M. ( 2011 ). Neurofi bromatosis . In R. M. Kleigman , B. F. Stanton , N. F. Schor , J. W. St. Geme , and R. E. Behrman (eds) Nelson textbook of pediatrics , pp. 2046 \200 \2232048. Philadelphia, PA : Saunders . Johnston , M. V. ( 2011 ). Encephalopathies . In R. M. Kleigman , B. F. Stanton , N. F. Sch or , J. W. St. Geme , and R. E. Behrman (eds) Nelson textbook of pediatrics , pp. 2061 \200\2232068. Philadelphia, PA : Saunders . Schiff , W. B. , Holtz , K. D. , Peterson , N. , and Rakusan , T. ( 2001 ). Eff ect of an i ntervention to reduce procedural pain and distress for children with HIV infection . J Pedi atr Psychol , 26 , 417 \200\223427. Josephs , J. S. , Fleishman , J. A. , Korthuis , P. T. , Moore , R. D. , and Gebo , K. A. ( 2010 ). Emergency department utilization among HIV-infected patients in a multisite multis tate study . HIV Med , 11 , 74 \200\22384. Serchuck , L. K. , Williams , P. L. , Nachman , S. , Gadow , K. D. , Chernoff , M. , and Sc hwartz , L. ( 2010 ). Prevalence of pain and association with psychiatric symptom severity in perinatally HIV-infected children as compared to controls living in HIV-aff ected househ olds . AIDS Care , 22 , 640 \200\223648. Sermet-Gaudelus , I. , De Villartay , P. , De Dre uzy , P. , Clairicia , M. , Vrielynck , S. , Canoui , P. , et al . ( 2009 ). Pain in childr en and adults with cystic fi brosis: a comparative study . J Pain Symptom Manage , 38 , 281 \200\223290. Lane , N. ( 1998 ). Rheumatologic and musculoskeletal manifestations of HIV [Online]. Avail able at: < http://hivinsite.ucsf.edu/InSite?page=kb-04 \200\223 01 \200\22315 > (accessed 2 1 January 2012). Lolekha , K. , Chotpitayasunodh , T. , and Newman , C. J. 2004 . Pain: a common symptom in human immu nodefi ciency virus-infected Th ai children . Acta Paediatr , 93 , 891 \200\223898. R. , Chanthavanich , P. , Limkittikul , K. , Luangxay , Slater , M. E. , De Lima , J. , Campbell , K. , Lane , L. , and Collins , J. ( 2010 ). Opio ids for the management of severe chronic nonmalignant pain in children: a retrospective 1-y ear practice survey in a children \200\231s hospital . Pain Med , 11 , 207 \200\223214. Lundy , C. T. , Doherty , G. M. , and Fairhurst , C. B. ( 2009 ). Botulinum toxin type A in jections can be an eff ective treatment for pain in children with hip spasms and cerebral p alsy . Dev Med Child Neurol , 51 , 705 \200\223710. Luzuriaga , K. and Sullivan , K. L. ( 1998 ). Viral and immunopathogenesis of vertical HIV-1 infection . In P. A. Pizzo , and C. M. Wilfert (eds) Pediatric AIDS , pp. 89 \200\223104. Baltimore, MD : Williams and Wilkins . Straff ord , M. , Cahill , C. , Schwartz , T. , Yee , J. , Sethna , N. , and Berde , C. ( 1 991 ). Recogition and treatment of pain in pediatric patients with AIDS . J Pain Symptom Ma nage , 6 , 146 . UNAIDS. ( 2011 ). World AIDS day report . Geneva : UNAIDS . Van Dyke , R. B. , Wang , L. , and Williams , P. L. ( 2008 ). Toxicities associated with dual nucleoside reverse-transcrip tase inhibitor regimens in HIV- infected children . J Infect Dis , 198 , 1599 \200\2231608 . McComsey , G. A. , and Leonard , E. ( 2004 ). Metabolic complications of HIV therapy in children . AIDS , 18 , 1753 \200\2231768. Morris , A. M. , Elliott , E. J. , D \200\231Souza , R. M. , Antony , J. , Kennett , M. , a nd Longbottom , H. ( 2003 ). Acute fl accid paralysis in Australian children . J Paediatr C hild Health , 39 , 22 \200\22326. World Health Organization. ( 2011 a). Global HIV/AIDS response: epidemic update and health sector towards universal access, progress report 2011 [Online]. Available at: < www.who.int /hiv/pub/progress_report2011/en/index.html >. World Health Organization. ( 2011 b). WHO mod el list of essential medicines for children [Online]. Available at: < http://whqlibdoc.who. int/hq/2011/ a95054_eng.pdf >. Norval , D. , O \200\231 Hare , B. , and Matusa , R. ( 2006 ). HIV/AIDS . In A. Goldman , R . Hain , and S. Liben , (eds) Oxford textbook of palliative care for children , pp. 467 \200\223480. Oxford : Oxford University Press . Oleske , J. ( 2007 ). Pain relief for children with HIV/AIDS: a global imperative . [Online ]. < http://www.whocancerpain.wisc.edu > (accessed 28 November 2011). World Health Organization. the ( 2012 ). pharmacological treatment of persisting pain in children with medical illness es . [Online]. Available at: < http://whqlibdoc.who.int/ publications/2012/9789241548120_Gu idelines.pdf > WHO guidelines on Parkinson , K. N. , Gibson , L. , Dickinson , H. O. , and Colver , A. F. ( 2010 ). Pain in children with cerebral palsy: a cross-sectional multicentre European study . Acta Paediatr , 99 , 446 \200\223451. Pier , D. B. , Hallbergson , A. , and Peters , J. M. ( 2010 ). Guillain-Barre syndrome in a child with pain: lessons learned from a late diagnosis . Acta Paediatr , 99 , 1589 \200 \2231591. Wilcox , C. ( 2010 ). Gastrointestinal consequences of infection with human immunodefi cien cy virus . In M. Feldman , L. S. Friedman , and L. J. Brandt , (eds) Sleisenger and Fordtra n \200\231s gastrointestinal and liver disease , pp. 523 \200\223536. Philadelphia, PA : S aunders . Ravilly , S. , Robinson , W. , Suresh , S. , Wohl , M. E. , and Berde , C. B. ( 1996 ). Chronic pain in cystic fi brosis . Pediatrics , 98 , 741 \200\223747. Yaster , M. and Schechter , N. ( 1996 ). Pain and human immunodefi ciency virus infection in children . Pediatrics , 98 , 455 \200\223456. Riquelme , I. , Cifre , I. , and Montoya , P. ( 2011 ). Age-related changes of pain experie nce in cerebral palsy and healthy individuals . Pain Med , 12 , 535 \200\223545. Yogev , R. C. , and Chadwick , E. G. ( 2011 ). Acquired immunodefi ciency syndrome . In R. M. Kleigman , B. F. Stanton , N. F. Schor , J. W. St. Geme , and R. E. Behrman (eds) Nelson textbook of pediatrics , 1157 \200\2231176. Philadelphia, PA : Saunders . Robinson , W. M. , Ravilly , S. , Berde , C. B. , and Wohl , M. E. ( 1997 ). End-of-life care in cystic fi brosis . Pediatrics , 100 , 205 \200\223209. CHAPTER 33 Common pain problems in the outpatient setting F. Ralph Berberich and Neil L. Sc hechter Summary Th is chapter will review key concepts pertaining to pediatric pain relief in offi ce settings. Included are general principles important to achieve pain reduction, pain attr ibuted to normative develop- mental processes such as teething, colic, and \200\230growing pains \200\231, pain from infections such as otitis media and pharyngitis, and pain from m inor procedures. Th ere is enormous individual variability in response to a painful stimulus Pain is a compl ex multifactorial phenomenon with enormous variation from person to person. Th ere is no pr edictable level of pain response for a given nociceptive stimulus. Th e pain experience for any child is a composite of various factors including temperament, age, previous experienc e, parental response, social modeling, genetic predisposi- tions, and psychological state ( Blount et al., 2008 ; McMurtry et al., 2010; Schechter et al., 2007 , 2010). A clinician wh o knows the child and family well can anticipate how the child might respond based on uniqu e attributes of the child and his or her previous response to pain- ful procedures. Clinici ans also can benefi t from the parent \200\231s in-depth knowledge of the child. Awareness of prior reactions, temperamental characteristics, and family dynamics may suggest non-phar macologi- cal strategies and stave off more aggressive interventions. Introduction Unfortunately, many advances in pediatric pain management have not been applie d to the pediatric offi ce (Berberich and Schechter, 2012 ). For example, despite their exp onential increase in number, immunizations are oft en still administered in a manner simila r to the way they were 40 years ago, continuing to contribute to a rate of needle phobia of 10% or more. Furthermore, little research has been done on relieving the pain of otitis or pharyngitis, common problems which are a signifi cant source of discomfort. Th e reasons f or this are mani- fold but certainly due at least in part to the less dramatic and oft en e phemeral nature of pain in the offi ce. Th ere exists additional concern that systematicall y addressing these issues might reduce offi ce pro- ductivity and effi ciency. Despite thes e barriers, addressing pain may prevent some of its short- and long-term consequences. Addi tionally, attention to pain is likely to enhance the relationship between the phy- sician a nd the child and his or her family (Schechter et al., 2007 ). Explanation and guidance regarding pain may help reduce it Anticipatory guidance has become a cornerstone of pediatric practice. Although children display signifi cant individual dif f er- ences, they develop, in general, predictable sequences that allow us to anticipate wh at their challenges will be. Routinely incorporating information about pain into well child visits may allow children and families to prepare for, and appropriately cope with, the pa in- ful experiences that arise during childhood. Th is includes identi- fying helpful indiv idualized strategies as well as recognizing when analgesics may be of value, and how best t o use them. Two of the constructs are discussed in the following two sections. General principles Th e offi ce based clinician, who typically has a long-term relationship with the child and family, and is well versed in child development, is in position to inco rporate the principles of pain reduction into the practice setting. By doing so, he or she can lower the cumulative impact and memory of repeated \200\230minor \200\231 painful insu lts (Von Baeyer et al., 2004 ). He or she can perhaps prevent the development of nee- dle p hobia, teach parents to provide comfort for their children, and reduce the anticipatory fea r and anxiety that oft en surrounds visits to a health care professional (Schechter et al., 2010 ). Development of a pediatric offi ce that routinely employs the following principles will improve the quality of life not only for the child and his or her family but also for the pediatric offi ce staff (Schechter et al., 2010 ). Anticipate and/or prevent pain whenever possible Th e importance of anticipating pain and t he prompt use of pain reduction strategies should be emphasized at the outset of the phy- s ician \200\223patient relationship. Pain may be more easily controlled if it can be prevent ed or addressed early on. Clinicians should give information about medication dosing and sa fe intervals between doses. Parents should understand that pain medication can be given pro actively in anticipation of pain aft er injury or during illness or before procedures such as venepuncture. When a medication is appropriate for either pain or fever, parents should be instructed not to omit that medication \200\230because there is no fever \200\231. CHAPTER 33 common pain problems in the outpatient setting 329 Promote self-mastery in the child Teaching children techniques that can allow them to contr ol their pain decreases the helplessness that they may feel when confronted with a painful situation. Th e clinician periodically can support and reinforce the importance of particip atory distraction and encour- age parents to identify the most appropriate and eff ective c oping measures for their child. Th ey best know their child \200\231s temperament, and the strategies that have been eff ective previously. Measures such as singing a song together, reading a story, watching a video, are ways to reduce the \200\230bother \200\231 and trau ma of a painful or fright- ening event. Th ese techniques, as well as others incorporated i nto an immunization sequence, can diminish the pain response and its associated anxiety (Be rberich and Landman, 2009 ). Many of these techniques could be practiced at home to enhance their mastery. As the child grows, the clinician can remind parents to bring along stuff e d animals, books, or smartphones and to help engage in self- calming non-procedural talk an d activities. Parents should learn that it helps to look forward to something pleasurable, i.e. \200\230When we \200\231ve fi nished here, then we can \200\231 child through painful procedures in the offi ce. When medically safe, upright comfort posit ioning, oft en on a parent \200\231s lap, is the best choice for the examination or any pro cedure that could be seen as inva- sive (Lacey et al., 2008 ; Schechter et al., 2007 ; Spar ks et al., 2007 ). If restraint on an exam table is required, positioning a parent near the child \200\231s head and seeking cooperative possibilities reduces anxiety.