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Background: Age reportedly affects headache prevalence differently in boys and girls. However, little empirical data exists regarding pediatric headache prevalence and headache-related burden in children and adolescents according to age and sex. In the present study, we considered age and sex while evaluating the distribution, characteristics, and impairment of primary headache disorders at a pediatric headache center in Germany. Methods: Medical records of children and adolescents attending the headache clinic of the Interdisciplinary Pain Center of the Carl Gustav Carus University Hospital in Dresden during the period 2015-2022 were retrospectively grouped and analyzed depending on age (< or ≥14 years) and sex. Results: The study population consisted of 652 children and adolescents, aged between 3 and 18 years. Almost two-thirds of the patients (≈60%) were females, and almost two-thirds of these females (58%) were ≥14 years of age. Generally, the most prevalent headache diagnoses as defined by the International Classification of Headache Disorders 3rd edition were episodic migraine without aura and the combination of tension-type headache and episodic migraine with or without aura i.e., mixed-type headache (each ≈27%). In the younger group (<14 years), the mixed-type headache was the most prevalent in girls (28.6%), whereas, for boys, episodic migraine without aura was the most prevalent headache diagnosis (47.4%). In the older group (≥14 years), the mixed-type headache continued to be the most prevalent for girls (30%), and it became the most prevalent for boys (26.3%). Before the age of 14, about 16% of children were severely affected by their headaches. After the age of 14, this proportion increased to roughly one-third (33%) of adolescents, driven mainly by teenage girls (26%) who were severely affected by their headaches. Furthermore, the prevalence of comorbidities was significantly higher among girls (67%), particularly in the adolescent group (74%). Conclusions: Our data shows that headache disorders in a specialized pediatric clinic impose a significant burden, especially among teenage girls indicating high therapy needs. Enhancing awareness of early diagnosis and preventive care is crucial to mitigate the development of chronic headaches, and mitigate their adverse effects on life quality and educational capability. [ABSTRACT FROM AUTHOR]

The bone morphogenetic protein (BMP) family is a class of transforming growth factor (TGF-[beta]) superfamily molecules that have been implicated in neuronal differentiation. We studied the effects of BMP2 and glial cell line-derived neurotrophic factor (GDNF) on inducing differentiation of enteric neurons and the signal transduction pathways involved. Studies were performed using a novel murine fetal enteric neuronal cell line (IM-FEN) and primary enteric neurons. Enteric neurons were cultured in the presence of vehicle, GDNF (100 ng/ml), BMP2 (10 ng/ml), or both (GDNF + BMP2), and differentiation was assessed by neurite length, markers of neuronal differentiation (neurofilament medium polypeptide and [beta]-III-tubulin), and neurotransmitter expression [neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) and Substance P]. BMP2 increased the differentiation of enteric neurons compared with vehicle and GDNF-treated neurons (P < 0.001). BMP2 increased the expression of the mature neuronal markers (P < 0.05). BMP2 promoted differentiation of NPY-, nNOS-, and TH-expressing neurons (P < 0.001) but had no effect on the expression of cholinergic neurons (CHAT, Substance P). Neurons cultured in the presence of BMP2 have higher numbers of TH-expressiug neurons after exposure to 1-methyl 4-phenylpyridinium ([MPP.sup.+]) compared with those cultured with [MPP.sup.+] alone (P < 0.01). The Smad signal transduction pathway has been implicated in TGF-[beta] signaling. BMP2 induced phosphorylation of Smad1, and the effects of BMP2 on differentiation of enteric neurons were significantly reduced in the presence of Smad1 siRNA, implicating the role of Smad1 in BMP2-induced differentiation. The effects of BMP2 on catecholaminergic neurons may have therapeutic implications in gastrointestinal motility disturbances. immorto; glial cell line-derived neurotrophic factor; bone morphogenic protein 2; Smad1 doi:10.1152/ajpgi.00343.2009.