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SYNOPSIS Endogenous opioids and 5‐hydroxytryptamine are the main neurotransmitters that regulate nociception, hedonia and autonomia. These functions are simultaneously impaired in idiopathic headaches. Enkephalins, beta‐endorphin, and tryptophan (5‐HT precursor) were evaluated in CSF and plasma of migraine and cluster headache sufferers. The following results were obtained:(a) decreased levels of CSF enkephalins in migraine attack and cluster headache,(b) increased CSF Tryptophan (TP) in migraine,(c) increased free plasma TP in migraine attack,(d) increased serum beta‐endorphin‐like‐immunore‐activity at the end of attack.A possible link between these findings and the impairment of nociception, hedonia and vegetative balance in headache sufferers is here discussed.

Beta-endorphin (RIA method, previous chromatographic extraction) was evaluated in plasma of migraine sufferers in free periods and during attacks. Decreased levels of the endogenous opioid peptide were found in plasma sampled during the attacks but not in free periods. Even chronic headache sufferers exhibited significantly lowered levels of beta-endorphin, when compared with control subjects with a negative personal and family history of head pains. The mechanism of the hypoendorphinaemia is unknown: lowered levels of the neuropeptide, which controls nociception, vegetative functions and hedonia, could be important in a syndrome such as migraine, characterized by pain, dysautonomia and anhedonia. The impairment of monoaminergic synapses ("empty neuron" condition) constantly present in sufferers from serious headaches, could be due to the fact that opioid neuropeptides, because of a receptoral or metabolic impairment, poorly modulate the respective monoaminergic neurons, resulting in imbalance of synaptic neurotransmission.

Indomethacin, a new nonsteroid anti-inflammatory agent causes headache, a marked decrease in cerebrospinal fluid pressure, and an increase in retinal arterial pressure, while it produces little and inconstant change in the pressure of the carotid and brachial arteries. Despite the headache, indomethacin was investigated in sub;ects with vascular headache because of its vasoconstrictor action. Clinical improvement similar 01' slightly inferior to that with ergotamine was observed.

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