Synthetic oligonucleotides were used to screen a rat striatal cDNA library for sequences corresponding to the tachykinin peptides substance P and neurokinin A. The cDNA library was constructed from RNA isolated from the rostral portion of the rat corpus striatum, the site of striatonigral cell bodies. Two types of cDNAs were isolated and defined by restriction enzyme analysis and DNA sequencing to encode both substance P and neurokinin A. The two predicted preprotachykinin protein precursors (130 and 115 amino acids in length) differ from each other by a pentadecapeptide sequence between the two tachykinin sequences, and both precursors possess appropriate processing signals for substance P and neurokinin A production. The presence of a third preprotachykinin mRNA of minor abundance in rat striatum was established by S1 nuclease protection experiments. This mRNA encodes a preprotachykinin of 112 amino acids containing substance P but not neurokinin A. These three mRNAs are derived from one rat gene as a result of differential RNA processing; thus, this RNA processing pattern further increases the diversity of products that can be generated from the preprotachykinin gene.

Background: For adults, disability produced by migraines has been assessed with a migraine-specific disability tool—MIDAS. The objective of this study was to develop and validate a similar tool that accurately depicts the disability of headaches in school-age children and adolescents. Methods: A six-question tool (PedMIDAS) was developed and administered to patients attending a tertiary referral center for pediatric headaches. Internal consistency and test/retest reliability were assessed. Validity was assessed by correlating scores with headache frequency, severity, and duration. Changes in the total score in response to treatment were assessed in a portion of the patients. Results: The PedMIDAS questionnaire was administered to 441 patients for a total of 724 trials. The mean score at the initial visit was 44.3 ± 47.9, whereas the overall mean score was 25.1 ± 36.5. A 2-week test/retest reliability assessment for 56 patients confirmed the stability of the instrument with a Pearson coefficient of 0.80. The correlation of the PedMIDAS score with frequency, severity, and duration had Pearson’s coefficient values of 0.58, 0.27, and 0.23. The PedMIDAS score was reduced to 20.0 ± 32.3 (p < 0.0001) at the first follow-up assessment with subsequent continued reduction. Conclusions: The PedMIDAS questionnaire provided a developmentally sensitive, reliable, and valid assessment of the disability of childhood and adolescent headaches. This questionnaire provides a tool to assess the impact of migraines in children and to monitor response to treatment. Further research should focus on additional validation of the PedMIDAS using a larger population and sampling from other populations (e.g., primary care and community samples).

Objective: To review evidence on the pharmacologic treatment of the child with migraine headache. Methods: The authors reviewed, abstracted, and classified relevant literature. Recommendations were based on a four-tiered scheme of evidence classification. Treatment options were separated into medications for acute headache and preventive medications. Results: The authors identified and reviewed 166 articles. For acute treatment, five agents were reviewed. Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs placebo. Acetaminophen is probably effective and is well tolerated vs placebo. Rizatriptan and zolmitriptan were safe and well tolerated but were not superior to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is probably effective. The data concerning cyproheptadine, amitriptyline, divalproex sodium, topiramate, and levetiracetam were insufficient. Conflicting data were found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine did not show efficacy. Conclusions: For children (>age 6 years), ibuprofen is effective and acetaminophen is probably effective and either can be considered for the acute treatment of migraine. For adolescents (>12 years of age), sumatriptan nasal spray is effective and should be considered for the acute treatment of migraine. For preventive therapy, flunarizine is probably effective and can be considered, but is not available in the United States. There are conflicting or insufficient data to make any other recommendations for the preventive therapy of migraine in children and adolescents. For a clinical problem so prevalent in children and adolescents, there is a disappointing lack of evidence from controlled, randomized, and masked trials.

Objective. Despite the high prevalence of headaches in youths, quality of life (QOL) has not been well examined. We examined QOL in a clinical sample of children with headaches and compared it with children with other chronic diseases. Methods. A survey study was conducted of 572 consecutive patients (mean age, 11.4 ± 3.6 years) who presented with headaches to a children’s headache center. Children and parents completed the Pediatric Quality of Life Inventory, Version 4.0 and a standardized headache assessment. Results were compared with established norms for healthy and chronically ill children. Results. Most patients (99%) had a clinical diagnosis of migraine: 85% met the International Headache Society migraine criteria, and 40% had chronic daily headaches. Total Pediatric Quality of Life Inventory, Version 4.0 score was lower for the entire group (73.1 ± 14.4) compared with healthy norms (83.0 ± 14.8) and lowest for children with chronic daily headaches (70.5 ± 15.5). The impact on QOL of children with migraine was similar to that of children with arthritis and cancer. Conclusions. QOL of children with headaches is significantly affected by their health condition. The impact of headaches on QOL is similar to that found for other chronic illness conditions, with impairments in school and emotional functioning being the most prominent.

The primary aim of this study was to describe pain characteristics, coping strategies, depression, and functional disability in children and adolescents with chronic pain and to examine potential factors that are associated with functional disability in a pediatric pain population. The secondary aim of this study was to compare functional disability in two chronic pain conditions: localized musculoskeletal pain and chronic daily headaches. The participants in this study were 73 pediatric pain patients with a variety of chronic pain conditions. Subjects in the second part of the study were a subset of patients (N = 44) from the pain clinic sample with chronic localized musculoskeletal pain and a subset of patients (N = 38) from the headache center of the same hospital who had chronic daily headaches. Patients completed self-report measures of pain intensity, depression, coping strategies, coping efficacy, and functional disability. Results indicated that chronic pain had a substantial impact on the children's lives and that depression was strongly associated with functional disability. Maladaptive coping was correlated with depression and disability; however, maladaptive coping was not independently associated with functional disability. A comparison between the two groups found significant differences in pain intensity and functional disability. The localized musculoskeletal pain group reported higher levels of disability and more difficulty coping than the chronic daily headache group. The implications for treatment of chronic pain in children are discussed with an emphasis on greater attention to developmental issues and their relation to coping, emotional functioning, and disability in pediatric pain. Further research examining differences in coping and disability between different pediatric pain groups is also warranted.

Substance P is a member of the tachykinin peptide family and participates in the regulation of diverse biological processes. The polymerase chain reaction and conventional library screening were used to isolate a complementary DNA (cDNA) encoding the rat substance P receptor from brain and submandibular gland. By homology analysis, this receptor belongs to the G protein-coupled receptor superfamily. The receptor cDNA was expressed in a mammalian cell line and the ligand binding properties of the encoded receptor were pharmacologically defined by Scatchard analysis and tachykinin peptide displacement as those of a substance P receptor. The distribution of the messenger RNA for this receptor is highest in urinary bladder, submandibular gland, striatum, and spinal cord, which is consistent with the known distribution of substance P receptor binding sites. Thus, this receptor appears to mediate the primary actions of substance P in various brain regions and peripheral tissues.