The Involvement of Trigeminal Substance P Neurons in Cluster Headache. An Hypothesis




Substance P (SP) neurons, with bipolar axons from the cell body, in sensory ganglia, exhibit unique properties in that impulses may travel either orthodromically or antidromically in the various ramifications of the axons, and that the transmitter may be released both in the central and peripheral ends of the neuron. Thus, these nerves are not only sensory, carrying nociceptive impulses from the periphery, but also motor with ability to dilate blood vessels, constrict smooth muscle cells and cause protein extravasation, glandular secretion, release from mast cells and excitation of autonomic ganglion cells. Within the individual neuron several local reflex arches - axon reflexes - are established in this way.

An hypothesis is forwarded about the pathophysiology of cluster headache, against the background of recent morphological and functional evidence for SP neurons in the ipsilateral trigeminal nerve and its connections to various cranial structures including the sphenopalatine (pterygopalatine) ganglion and internal carotid perivascular nerve plexus. Activation of SP fibers in the ophthalmic and maxillary divisions may give rise to practically all symptoms of an attack of cluster headache. This provides a rational explanation for the beneficial effect on both pain and vegetative symptoms achieved by blockade of the Gasserian or sphenopalatine ganglia in this disease. A temporary arrest of central inhibitory serotonergic impulses presynaptically on the SP neurons in the caudal trigeminal nucleus is, with our present knowledge, a likely explanation for such an activation, even if it may not be the only factor. A comparison is made with the present opinion on activation of parasympathetic and blockade of sympathetic nerves to explain the various symptoms of a cluster attack.