Activation of trigeminal brain stem neurons by chemical stimulation of the dura mater encephali--preparation for studying meningeal nociception in the rat

Abstract

Headache is thought to be generated by nociceptive processes within the meninges, followed by activation of trigeminal neurons within the brainstem. The noxious stimuli initially involved in these nociceptive processes are unknown. A preparation was developed in the barbiturate-anesthetized rat, in which the activation of trigeminal brain stem neurons by selective local stimulation of the dura mater could be observed. The dura mater encephali was exposed by trepanizing the parietal bone up to the sagittal superior sinus. The surface of the dura was stimulated with electrical pulses using bipolar electrodes. Extracellular recordings were made from neurons in the subnucleus interpolaris and caudalis of the spinal trigeminal nucleus. Neurons driven by meningeal afferents were identified by electrical stimulation and by probing their receptive fields on the dura mater. For chemical stimulation a combination of several inflammatory mediators (bradykinin, serotonin, histamine and prostaglandin E(2), each 10(-4)M, 6.1) was topically applied to the dura mater or injected through a catheter into the sagittal sinus. Most of the trigeminal brain stem neurons with input from the parietal dura mater had convergent input from the facial skin with preponderance of the periorbital region. A high proportion of neurons (69%) could be activated by the combination of inflammatory mediators administered to the dura mater. We conclude that chemical stimuli activating the meningeal nociceptive system may play a decisive role in the generation of headache. This is particularly relevant for the nociceptive processes during neurogenic inflammation, which is believed to be an important step in the pathophysiology and development of migraine pain. The preparation presented here may be a valuable model for further studying the neurophysiological changes that are involved in the generation of headache.