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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 structures of the intracranial meninges1,2. Although the recurrent headache of migraine is of unknown origin and is not accompanied by an identifiable pathology, it shares with intracranial headaches features that suggest an exaggerated intracranial mechanosensitivity (worsening of the pain by coughing, breath-holding or sudden head movement1,3). One possible basis for such symptoms would be a sensitization of meningeal 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 investigated the possible occurrence of sensitization4–12. We have recorded the activity of primary afferent neurons in the rat trigeminal ganglion that innervate the dural venous sinuses. Chemical stimulation of their dural receptive fields with inflammatory mediators both directly excited 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 intracranial mechanical hypersensitivity that is characteristic of some types of clinically occurring headaches, and may also contribute to the throbbing pain of migraine.

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  1. Wolff, H. G. Headache and Other Head Pain (Oxford Univ. Press, New York, 1963).

    Google Scholar 

  2. Martin, J. B. in Harrison's Principles of Internal Medicine 12th edn (eds Wilson, J. D. et al.) 108–115 (McGraw-Hill, New York, 1991).

    Google Scholar 

  3. Blau, J. N. & Dexter, S. L. Cephalalgia 1, 143–147 (1981).

    CAS  Article  Google Scholar 

  4. Strassman, A. S., Mason, P., Moskowitz, M. & Maciewicz, R. J. Brain Res. 379, 242–250 (1986).

    CAS  Article  Google Scholar 

  5. Davis, K. D. & Dostrovsky, J. O. J. Neurophysiol. 59, 648–666 (1988).

    CAS  Article  Google Scholar 

  6. Davis, K. D. & Dostrovsky, J. O. Brain Res. 446, 401–406 (1988).

    CAS  Article  Google Scholar 

  7. Davis, K. D. & Dostrovsky, J. O. Brain Res. 454, 89–100 (1988).

    CAS  Article  Google Scholar 

  8. Zagami, A. S. & Lambert, G. A. Exp. Brain Res. 81, 552–566 (1990).

    CAS  Article  Google Scholar 

  9. Zagami, A. S. & Lambert, G. A., Neurosci. Lett. 121, 187–190 (1991).

    CAS  Article  Google Scholar 

  10. Lambert, G. A., Zagami, A. S., Bogduk, N. & Lance, J. W. Cephalalgia 11, 75–85 (1991).

    CAS  Article  Google Scholar 

  11. Dostrovsky, J. O., Davis, K. D. & Kawakita, K. Can. J. Physiol. Pharmacol. 69, 652–658 (1991).

    CAS  Article  Google Scholar 

  12. Kaube, H., Hoskin, K. L. & Hoskin, K. L. & Goadsby, P. J. Cephalalgia 12, 133–136 (1992).

    CAS  Article  Google Scholar 

  13. Penfield, W. & McNaughton, M. Arch. Neurol. Psychiat. 44, 43–75 (1940).

    Article  Google Scholar 

  14. Andres, K. H., von During, M., Muszynski, K. & Schmidt, R. F. Anat. Embryol. 175, 289–301 (1987).

    CAS  Article  Google Scholar 

  15. Moskowitz, M. A. & Macfarlane, R. Cerebrovasc. Brain Metab. Rev. 5, 159–177 (1993).

    CAS  PubMed  Google Scholar 

  16. Strassman, A. M., Mineta, Y. & Vosr, B. P. J. Neurosci. 14, 3725–3735 (1994).

    CAS  Article  Google Scholar 

  17. Steen, K. H., Reeh, P. W., Anton, F. & Handwerker, H. O. J. Neurosci. 12, 86–95 (1992).

    CAS  Article  Google Scholar 

  18. Davis, K. D., Meyer, R. A. & Campbell, J. N. J. Neurophysiol. 69, 1071–1081 (1993).

    CAS  Article  Google Scholar 

  19. Baker, D. G., Coleridge, H. M., Coleridge, J. C. G. & Nerdrum, T. J. Physiol. 306, 519–536 (1980).

    CAS  Article  Google Scholar 

  20. Schaible, H.-G. & Schmidt, R. F. J. Physiol. (Lond.) 403, 91–104 (1988).

    CAS  Article  Google Scholar 

  21. Graham, J. R. & Wolff, H. G. Arch. Neurol. Psychiatr. 39, 737–763 (1938).

    CAS  Article  Google Scholar 

  22. Friberg, L., Olesen, J., Iversen, H. K. & Sperling, B. Lancet 338, 13–17 (1991).

    CAS  Article  Google Scholar 

  23. Iversen, H. K., Nielsen, T. H., Olesen, J. & Tfelt-Hansen, P. Lancet 336, 837–839 (1991).

    Article  Google Scholar 

  24. Thomsen, L. L., Iversen, H. K. & Olesen, J. Cephalalgia 15, 109–116 (1995).

    CAS  Article  Google Scholar 

  25. Woolf, C. J. Nature 308, 686–688 (1983).

    ADS  Article  Google Scholar 

  26. Burstein, R., Malick, A. & Strassman, A. Soc. Neurosci Abstr. 22, 864 (1996).

    Google Scholar 

  27. Daley, M. L., Pasupathy, H., Griffith, M., Robertson, J. T. & Leffler, C. W. IEEE Trans. Biomed. Eng. 42, 420–424 (1995).

    CAS  Article  Google Scholar 

  28. Lauritzen, M. Brain 117, 199–210 (1994).

    Article  Google Scholar 

  29. Goadsby, P. J. & Edvinsson, L. Ann. Neurol. 33, 48–56 (1993).

    CAS  Article  Google Scholar 

  30. Orr, E. L. & Stokely, M. E. Soc. Neurosci. Abstr. 21, 1858 (1995).

    Google Scholar 

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Strassman, A., Raymond, S. & Burstein, R. Sensitization of meningeal sensory neurons and the origin of headaches. Nature 384, 560–564 (1996).

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