[Brain network dysfunctions as substrates of primary headaches]

Abstract

A large body of clinical and pre-clinical evidence has shown complex interactions between bottom-up and top-down mechanisms that are essential for the discrimination of noxious information and pain perception. These endogenous systems, mainly originating from the brainstem, hypothalamus and cerebral cortex, are strongly influenced by behavioral, cognitive and emotional factors that are relevant for the survival of the individual. Under pathological conditions, however, dysfunctional engagement of these descending pathways certainly contributes to the transformation from acute into chronic pain states. In disorders such as primary headaches, dysfunctions affecting brain regulation mechanisms contribute to the generation of episodic painful states in susceptible individuals, and to the evolution from acute to chronic migraine or cluster headache. Taken together, these studies support the concept that CNS mechanisms that process trigemino-vascular pain do not consist only of a bottom-up process, whereby a painful focus modifies the inputs to the next higher level. Indeed, several CNS regions mediate subtle forms of plasticity by adjusting neural maps downstream and, consequently, altering all the modulatory mechanisms as a result of sensory, autonomic, endocrine, cognitive and emotional influences. Disturbances in normal sensory processing within these loops could lead to maladaptive changes and impaired craniofacial functions at the origin of primary headaches.