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Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch

Abstract

We found a class of lamina I spinothalamic tract (STT) neurons selectively excited by iontophoretic histamine. The responses of this class of neurons parallel the pure itching sensation this stimulus elicits in humans, and match the responses of peripheral C-fibers that have similar selectivity. These neurons have distinct central conduction velocities and thalamic projections, indicating that they constitute a unique subset of STT neurons. These findings can explain why a lesion of the lateral STT disrupts itch along with pain and temperature sensations. Our findings provide strong evidence that itch is subserved by specific neural elements both peripherally and centrally.

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Figure 1: Responses from a histamine-sensitive lamina I STT neuron.
Figure 2: Histamine and vehicle evoked responses from histamine-sensitive lamina I STT neurons.
Figure 3: The effects of histamine and vehicle on a nociceptive lamina I STT neuron.
Figure 4: Distinguishing features of histamine-sensitive lamina I STT neurons.
Figure 5: Response properties of chemo-nociceptive lamina I STT neurons.

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References

  1. Hales, P. Pruritis after epidural morphine. Lancet 2, 204 (1980).

    Article  CAS  Google Scholar 

  2. Duffy, B. L. Itching as a side-effect of epidural morphine. Anaesthesia 36, 67 (1981).

    Article  CAS  Google Scholar 

  3. Ballantyne, J. C., Loach, A. B. & Carr, D. B. Itching after epidural and spinal opiates. Pain 33, 149–160 (1988).

    Article  CAS  Google Scholar 

  4. Graham, D. T., Goodell, H. & Wolff, H. G. Neural mechanisms involved in itch, “itchy skin,” and tickle sensations. J. Clin. Invest. 30, 37–49 (1951).

    Article  CAS  Google Scholar 

  5. Hyndman, O. R. & Wolkin, J. Anterior cordotomy. Arch. Neurol. Psychiatry (Lond.) 50, 129–148 (1943).

    Article  Google Scholar 

  6. Nathan, P. W. Touch and surgical division of the anterior quadrant of the spinal cord. J. Neurol. Neurosurg. Psychiatry 53, 935–939 (1990).

    Article  CAS  Google Scholar 

  7. Tuckett, R. P. & Wei, J. Y. Response to an itch-producing substance in cat. II. Cutaneous receptor populations with unmyelinated axons. Brain Res. 413, 95–103 (1987).

    Article  CAS  Google Scholar 

  8. Bickford, R. G. Experiments relating to the itch sensation, its peripheral mechanism, and central pathways. Clin. Sci. 3, 377–386 (1938).

    Google Scholar 

  9. LaMotte, R. H. in Neurobiology of Nociceptors (eds. Belmonte, C. & Cervero, F.) 390–417 (Oxford Univ. Press, New York, 1996).

    Google Scholar 

  10. Schmelz, M., Schmidt, R., Bickel, A., Handwerker, H. O. & Torebjörk, H. E. Specific C-receptors for itch in human skin. J. Neurosci. 17, 8003–8008 (1997).

    Article  CAS  Google Scholar 

  11. Magerl, W., Westerman, R. A., Möhner, B. & Handwerker, H. O. Properties of transdermal histamine iontophoresis: Differential effects of season, gender, and body region. J. Invest. Dermatol. 94, 347–352 (1990).

    Article  CAS  Google Scholar 

  12. Schmelz, M., Schmid, R., Handwerker, H. O. & Torebjörk, H. E. Encoding of burning pain from capsaicin-treated human skin in two categories of unmyelinated nerve fibres. Brain 123, 560–571 (2000).

    Article  Google Scholar 

  13. LaMotte, R. H., Shain, C. N., Simone, D. A. & Tsai, E. Neurogenic hyperalgesia: psychophysical studies on underlying mechanisms. J. Neurophysiol. 66, 190–211 (1991).

    Article  CAS  Google Scholar 

  14. Simone, D. A., Alreja, M. & LaMotte, R. H. Psychophysical studies of the itch sensation and itchy skin (“alloknesis”) produced by intracutaneous injection of histamine. Somatosens. Mot. Res. 8, 271–279 (1991).

    Article  CAS  Google Scholar 

  15. Handwerker, H. O., Forster, C. & Kirchoff, C. Discharge patterns of human C-fibers induced by itching and burning stimuli. J. Neurophysiol. 66, 307–315 (1991).

    Article  CAS  Google Scholar 

  16. Simone, D. A. et al. The magnitude and duration of itch produced by intracutaneous injections of histamine. Somatosens. Res. 5, 81–92 (1987).

    Article  CAS  Google Scholar 

  17. Jinks, S. L. & Carstens, E. Superficial dorsal horn neurons identified by intracutaneous histamine: chemonociceptive responses and modulation by morphine. J. Neurophysiol. 84, 616–627 (2000).

    Article  CAS  Google Scholar 

  18. Carstens, E. Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of histamine, capsaicin, and other irritants. J. Neurophysiol. 77, 2499–2514 (1997).

    Article  CAS  Google Scholar 

  19. McMahon, S. B. & Koltzenburg, M. Itching for an explanation. Trends Neurosci. 15, 497–501 (1992).

    Article  CAS  Google Scholar 

  20. Keele, C. A. & Armstrong, D. Substances Producing Pain and Itch (Edward Arnold, London, 1964).

    Google Scholar 

  21. Scott, D. W. in The Cornell Book of Cats (ed. Siegal, M.) 177–184 (Villard Books, New York, 1989).

    Google Scholar 

  22. Craig, A. D. Jr. & Kniffki, K.-D. Spinothalamic lumbosacral lamina I cells responsive to skin and muscle stimulation in the cat. J. Physiol. (Lond.) 365, 197–221 (1985).

    Article  CAS  Google Scholar 

  23. Craig, A. D. & Hunsley, S. J. Morphine enhances the activity of thermoreceptive cold-specific lamina I spinothalamic tract neurons in the cat. Brain Res. 558, 93–97 (1991).

    Article  CAS  Google Scholar 

  24. Craig, A. D. & Serrano, L. P. Effects of systemic morphine on lamina I spinothalamic tract neurons in the cat. Brain Res. 636, 233–244 (1994).

    Article  CAS  Google Scholar 

  25. Han, Z.-S., Zhang, E.-T. & Craig, A. D. Nociceptive and thermoreceptive lamina I neurons are anatomically distinct. Nat. Neurosci. 1, 218–225 (1998).

    Article  CAS  Google Scholar 

  26. Craig, A. D. & Bushnell, M. C. The thermal grill illusion: unmasking the burn of cold pain. Science 265, 252–255 (1994).

    Article  CAS  Google Scholar 

  27. Kress, M. & Reeh, P. W. in Neurobiology of Nociceptors (eds. Belmonte, C. & Cervero, F.) 284 (Oxford Univ. Press, New York, 1996).

    Google Scholar 

  28. Reeh, P. W., Kocher, L. & Jung, S. Does neurogenic inflammation alter the sensitivity of unmyelinated nociceptors in the rat? Brain Res. 384, 42–50 (1986).

    Article  CAS  Google Scholar 

  29. Schmidt, R. et al. Novel classes of responsive and unresponsive C-nociceptors in human skin. J. Neurosci. 15, 333–341 (1995).

    Article  CAS  Google Scholar 

  30. Green, B. G. Spatial summation of chemical irritation and itch produced by topical application of capsaicin. Percept. Psychophys. 48, 12–18 (1990).

    Article  CAS  Google Scholar 

  31. Craig, A. D. Spinal distribution of ascending lamina I axons anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) in the cat. J. Comp. Neurol. 313, 377–393 (1991).

    Article  CAS  Google Scholar 

  32. Musil, S. Y. & Olson, C. R. Organization of cortical and subcortical projections to anterior cingulate cortex in the cat. J. Comp. Neurol. 272, 203–218 (1988).

    Article  CAS  Google Scholar 

  33. Yasui, Y., Itoh, K., Kamiya, H., Ino, T. & Mizuno, N. Cingulate gyrus of the cat receives projection fibers from the thalamic region ventral to the ventral border of the ventrobasal complex. J. Comp. Neurol. 274, 91–100 (1988).

    Article  CAS  Google Scholar 

  34. Hseih, J.-C. et al. Urge to scratch represented in the human cerebral cortex during itch. J. Neurophysiol. 72, 3004–3008 (1994).

    Article  Google Scholar 

  35. Craig, A. D. in Forebrain Processing of Pain (ed. Besson, J. -M.) 13–25 (John Libbey, Paris, 1995).

    Google Scholar 

  36. Zhang, E.-T., Han, Z.-S. & Craig, A. D. Morphological classes of spinothalamic lamina I neurons in the cat. J. Comp. Neurol. 367, 537–549 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the NIH (NS 25616) and the Atkinson Pain Research Fund administered by the Barrow Neurological Foundation. We thank M. Tatum for technical support.

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Correspondence to D. Andrew.

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Andrew, D., Craig, A. Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 4, 72–77 (2001). https://doi.org/10.1038/82924

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