This Clinical Center will provide supportfor state-of-the-art clinical research activities for 962 SCO patients at St. Christopher's Hospital for Children (SCHC), Thomas Jefferson University Hospital (TJUH), Kosair Children's Hospital (KCH), and duPont Children's Hospital (DCH). Three of these sites (SCHC, KCH, TJUH) are currently part of the Marian Anderson Comprehensive (MAC) Sickle Cell Center and currently lead enrollment in several of the phase l/ll/lll Inter-Center studies sponsored by the Comprehensive Centers, also under the direction of Dr Dampier and Ms Rockstein through the MAC Center's Clinical Core. The Center PI and Center Chief Clinical coordinator at St. Christopher's Hospital are both credentialed by the Association of Clinical Research Professionals (Clinical Trial Investigator, and CRA certifications respectively) and have a several year record of successful coordination and supervision of research activities at the various Center sites. The proposed network clinical trials address important issues in clinical care of SCO patients. The first study is a phase IV of headache management that will build on descriptive and epidemiologic data being gather as part of the C-data project of the Comprehensive Center's Network. This study proposes a 4 month placebo controlled RCT of prophylactic therapy (amitryptline with or without CBT training) in children aged 7- 17 years with [unreadable] 2 headaches per month in the preceding 3 months, while a companion study will evaluate the effectiveness of amitriptyline or divalproex ER in reducing the number of days of recurrent headaches in a 4 month double blind, parallel treatment, placebo-controlled trial of adults with [unreadable] 2 migraine headaches per month. The second clinical trial will examine the efficacy of two alternative morphine PCA dosing regimens in comparison to a standard PCA therapy. It will also determine whether variations in morphine pharrnaco- cinetics, in morphine pharmacodynamics as determined by pharmacogenetics, or subject psychosocial 'actors, alter the efficacy of the various PCA regimens. An Outcomes Core is also proposed which will focus on developing a variety of outcome measures and descriptive clinical information to,support the appropriate , conduct of high quality clinical trials of therapies for sickle cell-related pain. The performance of these studies will advance the clinical understanding of sickle cell-related pain and its consequences. Their results will stimulate the development of innovative clinical trials of sickle pain.