SENSITIZATION OF MENINGEAL SENSORY NEURONS AND THE ORIGIN OF HEADACHES

THE headaches that accompany certain intracranial pathologies (such as meningitis, subarachnoid haemorrhage and tumour) have been considered to result from mechanical or chemical stimulation of pain-sensitive s tructures of the intracranial meninges(1,2). Although the recurrent he adache of migraine is of unknown origin and is not accompanied by an i dentifiable pathology, it shares with intracranial headaches features that suggest an exaggerated intracranial mechanosensititivity (worseni ng of the pain by coughing, breath-holding or sudden head movement(1,3 )). One possible basis for such symptoms would be a sensitization of m eningeal afferents to mechanical stimuli. Previous studies of neuronal responses to meningeal stimulation have focused primarily on cells in the central portion of the trigeminal pathway, and have not investiga ted the possible occurrence of sensitization(4-12). We have recorded t he activity of primary afferent neurons in the rat trigeminal ganglion that innervate the dural venous sinuses. Chemical stimulation of thei r dural receptive fields with inflammatory mediators both directly exc ited the neurons and enhanced their mechanical sensitivity, such that they were strongly activated by mechanical stimuli that initially had evoked little or no response, These properties of meningeal afferents (chemosensitivity and sensitization) may contribute to the intracrania l mechanical hypersensitivity that is characteristic of some types of clinically occurring headaches, and may also contribute to the throbbi ng pain of migraine.