**7. Conclusions**

Headache disorders represent both a treatment challenge and a serious public health con‐ cern, with major impact on the individual and society. Although the painful symptomatol‐ ogy is the main encounter for the decreased quality of life and discomfort, the vegetative manifestations which frequently accompany the cephalalgic syndromes, cause an impor‐ tant amount of distress. Despite the advancement of the understanding of the molecular basis of headache disorders and neurovascular complex interactions, both at central and peripheral levels, especially concerning migraine, there is still lack of an integrated view of the neurovegetative modulation in different types of primary cephalalgic syndromes, trans‐ lating from animal pathophysiologic "models" to clinical data. As shown in this chapter, the neurochemical mechanisms which subtend dysautonomic manifestations in different types of headache share common pathways, yet there is need to specifically address the various vegetative biomarkers in each type of headache, in order to provide more efficient and individualized therapeutic strategies, combining multimodal pharmacological and nonpharmacological approaches.

Without pretending exhaustively, this chapter highlights the need for a better and a more accurate characterization and classification of primary headaches, taking into consideration the whole spectrum of clinical manifestations, including the dysautonomic activity. Despite locally derived, population‐based data describing the burden of primary headache disorders, there is still need of a global perspective on disease impact, through both preclinical and clinical data, in both developed and developing countries, in order to maximize efforts for a better understanding and management of the disease.

## **Acknowledgements**

This work was supported by "Grigore T. Popa" University of Medicine and Pharmacy Iasi. Authors contributed equally to this work.

#### **conflict of interest**

The authors confirm that this chapter contents have no conflict of interest.
