Th e headache due to a brain tumor is the result of increased intracranial pressure due to the mass eff ect of the tumor or a block- age of cerebral spinal fl uid drainage. In additi on, the eff ects of the brain tumor on the surrounding tissue also induce changes in the ne urological examination or neurological symptoms (Lewis et al., 2002 ). Other symptoms of br ain tumor include seizures, ataxia, weakness, visual abnormalities, lethargy, and personali ty change in the majority of such patients \200\224the course will be progressive. Th e neu rological examination will be abnormal and the diagnosis can be confi rmed by neuroimaging. In any CNS infection, in addition to symptoms of increased intracranial pressure or progres sive neurological disease, mening- ismus, rash, or elevated temperature may be present. Ini tial evalu- ation should include a brain imaging procedure to rule out a mass lesion. If at all possible, this should be performed prior to any lum- bar puncture. Conclusion Th e majority of recurrent headaches in children and adolescents are primary hea daches. Secondary headaches, however, occur due to systemic or CNS disease. Th e history an d physical examination should help identify whether a headache is primary or secondary with appropriate laboratory tests and neuroimaging confi rming the suspicion. Ultimately, the d iagnosis of the secondary headache will be the resolution of the headache once the secondar y cause has been eff ectively treated, while persistence of recurrent headaches without the secondary cause helps confi rm the diagnosis and man- agement of primary headaches. Due to the continued growth of the tumor, the headache pat- tern is usually chronic, progre ssive, with increases in frequency and severity over time. Th e rapidity of the growth of t he tumor and the adaptability of the intracranial space to respond to this growth can modif y the timing of the headache \200\231s presentation. It is frequently reported to occur in the morning due to a \200\230ball-valve \200\231 eff ect in which the CSF pressure builds in the recumbent position and is relieved by posture \200\224the opposite of idiopathic int racranial hypertension. Substance-induced headache Prescribed medications, illicit drugs, dietary compounds, and to x- ins can cause headaches (Silberstein et al., 1998 ). Th ese substances may initiate a he adache, exacerbate a pre-existing headache, or cause headache on its withdrawal. A through history of exposure to medications and non-medications needs to be performed and removal or alteration of these substances, if possible, may be neces- sary before the headache respon ds. Stimulants used in the treat- ment of attention-defi cit disorder may initiate headache , especially if they are restarted at maximum dosage aft er not having been taken for sever al days to weeks. 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Col lins Summary Persisting pain in the context of medical illness has been recognized recently as a global problem by the World Health Organization (WHO, 2012). Whilst the epidemiology of me dical illness varies throughout the world, the general principles of pain management are ap plicable to most medical illnesses in children and are eff ec- tive. Successful pain manage ment for most children is contingent on the availability of the WHO model list of essential medicines for children (WHO, 2011), although regrettably not all medicines are available i n every country in the world. \227\206 Th e availability of medicines on the WHO model list of essential medicines for children (WHO, 2011b ). \227\206 Using a two-step strategy for analgesic prescription: simple anal- gesics for mil d pain (step 1), opioids for moderate to severe pain (step 2). \227\206 Dosing of analgesics at regular intervals when pain is constant ( \200\230by the clock \200\231). It is also recommended that children with per- sisting pain have medicines available for breakthrough pain. As there is insuffi cient evidence to recommend a particu lar opioid or route of administration for breakthrough pain in children, there is a need to make an appropriate choice of treatment modality based on clinical judgment, medicine avai lability, pharmaco- logical considerations, and patient related factors. Introduction Pain is commonly experienced by children in the context of medi- cal illness. Th is may be due to acute or short-lived pain related to procedures for diagnostic, treatme nt, or surgical interventions. Persisting pain refers to any long-term pain and medical ill nesses refers to specifi c situations of ongoing tissue damage where there is a clear role for pharmacological treatment. Persisting pain in child- hood illness implies the duration of pain is lasting beyond what would be expected from an acute injury. Th is latter is curr ently the subject of a WHO initiative to improve management of persisting pain in children due to medical illness (WHO, 2012 ). Th is chapter discusses persisting pain in the context of non-malignant disease (HIV/AIDS, cystic fi brosis, neurofi bromatosis, neuromuscular di s- ease, cerebral palsy) and confi nes itself to a discussion of pharma- cological manageme nt. Th e reader is referred to other sections of this book for the issues and management of persisting pain due to other conditions and for non-pharmacological strategies for pain ma nagement. \227\206 Using the simplest route of administration and avoiding the intra- muscular route ( \200\230by the mouth \200\231). Th e choice of alternative routes of administration when the oral route is not possible should be based on clinical judgment, availability, feasibi lity, and patient preference. \227\206 Tailoring treatment to the individual child ( \200\230by the individual \200\231) . Among other WHO recommendations, paracetamol and ibuprofen are the medicines of choice in t he fi rst step (mild pain) and morphine is recommended as the fi rst-line strong opioid for the treatment of persisting moderate to severe pain in children with medical illnesses. Th e selection of alternative opioid analgesics to morphine should be guided by consideration s of safety, availability, cost, and suitability, including patient-related factors. Switch ing opioids and/or route of administration in children is recommended in the presence of in ad- equate analgesic eff ect with intolerable side eff ects. Routine rotation of opioids is not recommended (WHO, 2012 ). Opioids for the management of non-malignant pain in childhood Data on the management of sev ere pain using opioids in children with non-malignant disease is limited. One retrospective review studied opioid prescription for chronic severe non-malignant pain in a multidiscipl inary pediatric pain clinic. During a 12-month period, 104 patients were seen in the clinic , of which 49 received an opioid as part of their pain management; 11 received an opioid fo r more than 3 months, and fi ve of these were still receiving an opioid at the end of the s tudy period. Overall, there appeared to be better Th e pharmacological management of persisting pain in children with non-malignant illnesses Th e principles of pain management in the context of pediatric medical illness are broadly applicable to most disease processes. Th e correct use of analgesic medicines will relieve pain in most children with persisting pain due to medical illness and relies on the follow ing key concepts ( Box 32.1 ): SECTION 4 pain in specific populations and diseases 320