Chronic daily headache: biochemical and neurotransmitter abnormalities

Although chronic daily headache (CDH) represents one of the most relevant complaints of patients in headache centers, the mechanisms underlying the chronicization of head pain are poorly understood. Experimental animal models of chronic pain suggest the involvement of a functional disturbance of several neuronal pathways. The disturbances include an abnormal excitability of nociceptive fibers supplying pain-sensitive structures in the brain responsible for peripheral sensitization (chronic neurogenic inflammation), an increased responsiveness of sensory neurons of the dorsal horns in the upper spinal cord and trigeminal nucleus caudalis (central sensitization), and a functional abnormality of facilitating and inhibitory supraspinal pathways. Moreover, based on the experimental chronic pain models, the concepts of hyperalgesia and allodynia, the phenomena of wind-up and kindling, and the suggestion of a long-term potentiation (LTP) inducing a “memory of pain” also in the head have been advocated to explain chronic head pain. However, these hypotheses have been only partially substantiated by robust findings in patients affected by CDH. In the last few years, investigation in patients with biochemical disturbances and neurotransmitter abnormalities in patients with CDH have been undertaken. Certain common mechanisms, but also discrepancies, have been identified between the two principal CDH forms, “ transformed migraine” and chronic tension-type headache. The biochemical and neurotransmitter alterations associated with analgesic and ergotamine abuse, which often is associated with CDH and the more recent triptan misuse, are at the moment only partially known. The most relevant results supporting the alteration of neurotransmitter pathways related to nociception in CDH are reviewed.