Meningeal nociception: electrophysiological studies related to headache and referred pain.

Headaches, which are usually referred to characteristic sites of the skull, are believed to involve meningeal nociceptors located in the dura mater encephali. Animal experiments show that these meningeal nociceptors are polymodal and usually highly sensitive to mechanical stimulation. These properties are also characteristic for the second order neurons in the spinal trigeminal nucleus, most of which receive convergent input from facial receptive sites. Sensitization of primary and secondary neurons by chemical irritants to mechanical stimuli may be an important mechanism in the generation of headaches. The convergent input from extracranial structures, which seems to be differentially organized in rodents and man, may explain the typical features of referred headache. Targets for analgesics used in the therapy of headaches (non-steroidal antiinflammatory drugs, 5-HT(1) receptor agonists) are probably meningeal nociceptors and different sites of the central trigeminal nociceptive and antinociceptive pathways.