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The Neurohistology and Neurophysiology of the Itch Sensation in Man

The Neurohistology and Neurophysiology of the Itch Sensation in Man Abstract The skin is a vast sentient surface, attuned to numerous environmental changes. Although it was first viewed as representing only the fifth sense, i. e., touch, the last century of research has disclosed that the skin is a far more complex sensory receptor. This area of study has long been an actively disputative one, and indeed within the year critical essays have challenged all previously held concepts of both the form and the function of sensory receptors in the skin of man. It is our purpose to review the field of knowledge concerning the itch sensation in man, to report experimental observations of our own, and to attempt an interpretative analysis of the neurophysiological basis for itching. The modern era of conceptual thinking on the problem of sensory reception in the skin began in 1838, when Johannes Müller1 enunciated his doctrine of specific energy, i. e., he References 1. The open bulla technique of Armstrong et al.65 invariably responds with pain, since it is hyperalgesic. 2. Müller, J.: Handbuch der Physiologie des Menschen , Ed. 2, Coblenz, 1838. 3. Volkmann, A. V.: in Handwörterbuch der Physiologie , edited by R. Wagner, Braunschweig, F. Vreiveg u. Sohn, 1842-1853, Vol. 2. 4. Blix, M.: Experimentelle Beiträge zur Lösung der Frage über die specifische Energie der Hautnerven , ztschr. Biol. , 20:141, 1884. 5. von Frey, M.: Physiologie des Sinnesorgane des menschlichen Haut , Ergebn. Physiol. 9:351, 1910.Crossref 6. Törok, L.: Über das Wesen der Juckempfindung , Ztschr. Psychol. , 46:23, 1907. 7. Titchener, E. B.: A Textbook of Psychology , New York, The Macmillan Company, 1909. 8. Winkler, F.: Studien über das Zustandekommen der Juckempfindung , Arch. Dermat. u. Syph. 99:273, 1910.Crossref 9. von Frey, M.: Zur Physiologie der Juckempfindung , Arch. néerl. physiol. 7:142, 1922. 10. Longo, V.: Sulla topografia della sensibilità del "prurito," Arch. fisiol. 36:197, 1936. 11. Rothman, S.: Beiträge zur Physiologie der Juckempfindung , Arch. Dermat. u. Syph. 139:227, 1922.Crossref 12. Head, H., and others: Studies in Neurology , London, Oxford University Press, 1920, Vol. 2. 13. Gasser, H. S.: Conduction in Nerves in Relation to Fiber Types , A. Research Nerv. & Ment. Dis. Proc. 15:35, 1934. 14. Heinbecker, P.; Bishop, G. H., and O'Leary, J. L.: Analysis of Sensation in Terms of the Nerve Impulse , Arch. Neurol., & Psychiat. 31:34, 1934. 15. Zotterman, Y.: Touch, Pain and Tickling: An Electrophysiological Investigation on Cutaneous Sensory Nerves , J. Physiol. 95:1, 1939. 16. Ranson, S. W.; Droegemueller, W. H.; Davenport, H. K., and Fisher, C.: Number, Size and Myelination of the Sensory Fibers in the Cerebrospinal Nerves , A. Research Nerv. & Ment. Dis. Proc. 15:3, 1934. 17. Lewis, T., and Pochin, E. E.: Double Pain Response of Human Skin to a Single Stimulus , Clin. Sc. 3:67, 1937. 18. Bickford, R. G.: The Fibre Dissociation Produced by Cooling Human Nerves , Clin. Sc. 4:159, 1939. 19. Graham, D. T.; Goodell, H., and Wolff, H. G.: Neural Mechanisms Involved in Itch, "Itchy Skin," and Tickle Sensations , J. Clin. Invest. 30:37, 1951. 20. Goldscheider, A.: Über Irradiation und Hyperästhesie im Bereich der Hautsensibilität. , Arch. ges. Physiol. 165:1, 1916. 21. Bickford, R. G.: Experiments Relating to Itch Sensation, Its Peripheral Mechanism and Central Pathways , Clin. Sc. 3:377, 1938. 22. Rothman, S.: Über die Juckempfindung in ekzematöser Haut , Arch. Dermat. u. Syph. 150:489, 1926. 23. Cormia, F. E.: Experimental Histamine Pruritus: I. Influence of Physical and Psychological Factors on Threshold Reactivity , J. Invest. Dermat. 19:21, 1952. 24. Sonnenschein, R. R.; Cornbleet, T.; Janowitz, H. D., and Grossman, M. I.: Inhibition of "Itchy Skin" with Tetraethylammonium , J. Invest. Dermat. 12:321, 1949. 25. Bishop, G. H.: The Skin as an Organ of Senses with Special Reference to the Itching Sensation , J. Invest. Dermat. 11:143, 1948. 26. Bishop, G. H.: Responses to Electrical Stimulation of Single Sensory Units of the Skin , J. Neurophysiol. 6:361, 1943. 27. Cormia, F. E., and Kuykendall, V.: Experimental Histamine Pruritus: II. Nature, Physical and Environmental Factors Influencing Development and Severity , J. Invest. Dermat. 20:429, 1953. 28. Cormia, F. E., and Kuykendall, V.: Experimental Histamine Pruritus: III. Influence of Drugs on the Itch Threshold , A. M. A. Arch. of Dermat. & Syph. 69:206, 1954. 29. Rajka, E.; Korossy, S., and Gozony, M.: Zur Pathogenese des Urtikariell entzündlichen Juckens , Dermatologica , 112:1, 1956. 30. Kepecs, J. G., and Robin, M.: Studies in Itching , A. M. A. Arch. Neurol. & Psychiat. 76:325, 1956. 31. Magnus, I. A., and Thompson, R. H.: Cholinesterase Levels in the Skin in Cholinogenic Urticaria and Pruritus , Brit. J. Dermat. 68:283, 1956. 32. Shelley, W. B., and Arthur, R. P.: Studies on Cowhage (Mucuna Pruriens) and Its Pruritogenic Proteinase, Mucunain , A. M. A. Arch. Dermat. 72:399, 1955. 33. Arthur, R. P., and Shelley, W. B.: The Role of Proteolytic Enzymes in the Production of Pruritus in Man , J. Invest. Dermat. 25:341, 1955. 34. Ungar, G.: Biochemical Mechanism of the Allergic Reaction , Internat. Arch. Allergy 4:258, 1953. 35. Sinclair, D. C.: Cutaneous Sensation and the Doctrine of Specific Energy , Brain 78:584, 1955. 36. Lele, P. P., and Weddell, G.: The Relationship Between Neurohistology and Corneal Sensibility , Brain , 79:119, 1956. 37. Schiller, F.: The Cutaneous Sensory Modalities: A Critique of Their "Specificity," A. M. A. Arch. Neurol. & Psychiat. 75:203, 1956. 38. Jones, M. H.: Second Pain: Fact or Artifact , Science 124; 442, 1956. 39. Ehrenwald, H., and Königstein, H.: Klinische und experimentelle Untersuchungen über das Juckgefühl , Wien. klin. Wchnschr. 42:1397, 1929. 40. Foerster, O.: Symptomatologic der Erkrankungen des Rückenmarks und seiner Würzeln , in Handbuch der Neurologie , edited by O. Bumke and O. Foerster, Berlin, Springer-Verlag, 1936, Vol. 5, p. 1. 41. McMurray, G. A.: Experimental Study of a Case of Insensitivity to Pain , Arch. Neurol. & Psychiat. 64:650, 1950. 42. Sjöqvist, O.: Studies on Pain Conduction in the Trigeminal Nerve , Acta Psychiat. et Neurol. (Supp. 17) , p. 1, 1938. 43. Hyndman, O. R., and Wolkin, J.: Anterior Cordotomy: Further Observations on Physiologic Results and Optimum Manner of Performance , Arch. Neurol. & Psychiat. 50:129, 1943. 44. Kahn, E. A.: Anterolateral Chordotomy for Intractable Pain , J. A. M. A. 100:1925, 1933. 45. Banzet, P. M.: La Cordotomie, Thesis, Paris, Libraire Louis Arnette, 1927. 46. Sicard, J. A., and Robineau, M.: Cordotomie laterale anterieure pour les algies incurable , Rev. Neurol. 1:21, 1925. 47. White, J. C. and Sweet, W. H.: Pain: Its Mechanisms and Neurosurgical Control , Springfield, Ill., Charles C Thomas, Publisher, 1955. 48. Melton, F. M., and Shelley, W. B.: The Effect of Topical Antipruritic Therapy on Experimentally Induced Pruritus in Man , J. Invest. Dermat. 15:325, 1950. 49. Macintosh, F. C.: Histamine-Releasing Drugs , Ann. Otol. Rhin. & Laryng. 65:385, 1956. 50. Benjamin, F. B.; Beerman, H., and Shelley, W. B.: Allergic Contact Dermatitis Due to Histamine-Releasing Drug 48-80 , A. M. A. Arch. Dermat. 71:190, 1955.Crossref 51. Sigel, H.: Cutaneous Sensory Threshold Stimulation with High Frequency Square-Wave Current: I. The Relationship of Electrode Dimensions to the Sensory Threshold , J. Invest. Dermat. 18:441, 1952. 52. Bishop, G. H.: A Simple Electronic Stimulator Suitable for Peripheral Nerve and Skin Sensory Testing , Electroencephalog. & Clin. Neurophysiol. 5:105, 1953. 53. Lee, R. E.; Williams, H. L., and Pfeiffer, C. C.: A Warm Wire Algesimeter , Fed. Proc. 8:314, 1949. 54. Arthur, R. P., and Shelley, W. B.: Paper in preparation. 55. Shelley, W. B., and Arthur, R. P.: Studies on Pruritus , Tr. A. Am. Physicians 69:285, 1956. 56. Bishop, G. H.: The Structural Identity of the Pain Spot in Human Skin , J. Neurophysiol. 7:185, 1944. 57. Weddell, G.; Palmer, E., and Pallie, W.: Nerve Endings in Mammalian Skin , Biol. Rev. 30:159, 1955. 58. Footnotes deleted on proof. 59. Melton, F. M., and Shelley, W. B.: The Effect of Topical Antipruritic Therapy on Experimentally Induced Pruritus in Man , J. Invest. Dermat. 15:325, 1950. 60. Broadbent, J. L.: Observations on Histamine-Induced Pruritus and Pain , Brit. J. Pharmacol. 10:183, 1955. 61. Shelton, J. M.: Distention Anesthesia for Minor Dermatological Procedures , A. M. A. Arch. Dermat. 75:130, 1957. 62. Nelson, P. G.: Action of Certain Enzymes on the Frog Node of Ranvier , Fed. Proc. 16:93, 1957. 63. West, P. M., and Hilliard, J.: Proteolytic Enzyme Inhibitors of Human Serum in Health and Disease , Proc. Soc. Exper. Biol. & Med. 71:169, 1949. 64. Leimdorfer, A., and Metzner, W. R. T.: Analgesia and Anesthesia Induced by Epinephrine , Am. J. Physiol. 157:116, 1949. 65. Armstrong, D.; Dry, R. M.; Keele, C. A., and Markham, J. W.: Observations on Chemical Excitants of Cutaneous Pain in Man. , J. Physiol. 120:326, 1953. 66. Adrian, E. D.: The Effects of Injury on Mammalian Nerve Fibers , Proc. Roy. Soc. London, (S. B.) 106:596, 1930. 67. Lele, P. P.; Sinclair, D. C., and Weddell, G.: The Reaction Time to Touch , J. Physiol. 123:187, 1954. 68. Landau, W. M. and Bishop, G. H.: Pain from Dermal, Periosteal and Fascial Endings, and from Inflammation , A. M. A. Arch. Neurol. & Psychiat. 69:490, 1953. 69. Ungar, G.: Mechanism of Histamine Release , in the Ciba Foundation Symposium on Histamine , Boston, Little Brown & Co., 1956, p. 431. 70. Magnus, I. A.: Personal communication to the authors, 1955. 71. Cormia, F.: Personal communication to the authors, 1956. 72. Feldberg, W.: On Some Physiological Aspects of Histamine , J. Pharm. & Pharmacol. 6:281, 1954. 73. Bowden, K.; Brown, B. G., and Batty, J. E.: 5-Hydroxytryptamine: Its Occurrence in Cowhage , Nature, London 174:925, 1954. 74. Tower, S. S.: Pain: Definition and Properties of the Unit for Sensory Reception. A. Research Nerv. & Ment. Dis., Proc. 23:16, 1943. 75. Beloff, A., and Peters, R. A.: Observations upon Thermal Burns; Influence of Moderate Temperature Burns upon Proteinase of Skin , J. Physiol. 103:461, 1945. 76. Smith, C. H., and Malkiewicz, G. M.: Role of the Automonic Nervous System in Intense Pruritus Ani , J. Internat. Coll. Surgeons 23:423, 1955. 77. Tomasch, J., and Britton, W. A.: On the Individual Variability of Fiber Composition in Human Peripheral Nerve , J. Anat. 90:337, 1956. 78. Tomasch, J., and Schwarzacher, H. G.: Die Innere Struktur peripherer menschlicher Nerven im Lichte faseranalytischer Untersuchungen , Acta Anat. 16:315, 1952.Crossref 79. Ito, F.: Experimental Studies on Itch Sensation: II. Influences of Arresting Blood Flow upon Itching, Pain and Touch Sensation , Nagoya J. M. Sc. 16:129, 1953. 80. Brink, F.; Bronk, D. W., and Larrabee, M. G.: Chemical Excitation of Nerve , Ann. New York Acad. Sc. 47:457, 1946.Crossref 81. Beecher, H. K.: The Powerful Placebo , J. A. M. A. 159:1602, 1955.Crossref 82. Lewis, T.: Pain , New York, The Macmillan Company, 1942. 83. Borelli, S., and Schott, S.: Pruritus (Übersichtstreferat über die Literatur von 1933 bis 1953) , Hautarzt 5:38, 1954. 84. Koenigstein, H.: Experimental Study of Itch Stimuli in Animals , Arch. Dermat. & Syph. 57:828, 1948. 85. Lewis, T.; Grant, R. T., and Marvin, H. M.: Vascular Reactions of the Skin to Injury , Heart 14:139, 1927. 86. Armstrong, D.; Dry, R. M. L.; Keele, C. A., and Markham, J. W.: Observations on Chemical Excitants of Cutaneous Pain in Man , J. Physiol. 120:326, 1953. 87. Ito, R., and Ito, F.: Experimental Studies on Itch Sensation: I. Stimulation and Narcotization by Itching Substances , Nagoya J. M. Sc. 16:107, 1953. 88. Feldberg, W., and Sherwood, S. L.: Behaviour of Cats After Intraventricular Injections of Eserine and DFP , J. Physiol. 125:488, 1954. 89. Mehes, J.: Experimentelle Untersuchungen über den Juckreflex am Tier. Arch. exper. Path. u. Pharmakol. 188:650, 1938. 90. Ivy, A. C.; Tanturi, C. A.; Hernandez, R., and Baroso, E.: Urticarial Reaction Induced in the Dog by Intravenous Injection of Sorbitol Monolaurate , Arch. Dermat. & Syph. 58:659, 1948. 91. Sherrington, C. S.: Observations on the Scratch Reflex , J. Physiol. 34:1, 1906. 92. Rothman, S., and others: Physiology and Biochemistry of the Skin , Chicago University of Chicago Press, 1954. 93. Rothman, S., and Shapiro, A. L.: Itching, in Signs and Symptoms , Ed. 3, edited by C. M. McBryde, Philadelphia, J. B. Lippincott Company, 1957. 94. Borelli, S., and Schott, S.: Pruritus: (Übersichtsreferat über die Literatur von 1933 bis 1953) , Hautarzt , 5:385, 1954. 95. Stigter, W.: Het Probleem van de Jeuk: Voorkomen en Functie van de Zenuwuiteinden in de Huid bij Mensen , Geneesk, bl. 47:1, 1955. 96. Granit, R.: Receptors and Sensory Perception , New Haven, Conn., Yale University Press, 1955. 97. Zotterman, Y.: Sensory Receptors , in Nerve Impulse: Transactions of the Fourth Conference , edited by D. Nachmansohn, New York, Josiah Macy, Jr., Foundation, 1954. 98. Sinclair, D. C.: Cutaneous Sensation and the Doctrine of Specific Energy , Brain 78:584, 1955. 99. Chatfield, P. O.: Fundamentals of Clinical Neurophysiology , Springfield, Ill., Charles C Thomas, Publisher, 1957. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png A.M.A. Archives of Dermatology American Medical Association

The Neurohistology and Neurophysiology of the Itch Sensation in Man

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References (107)

Publisher
American Medical Association
Copyright
Copyright © 1957 American Medical Association. All Rights Reserved.
ISSN
0096-5359
DOI
10.1001/archderm.1957.01550210020004
Publisher site
See Article on Publisher Site

Abstract

Abstract The skin is a vast sentient surface, attuned to numerous environmental changes. Although it was first viewed as representing only the fifth sense, i. e., touch, the last century of research has disclosed that the skin is a far more complex sensory receptor. This area of study has long been an actively disputative one, and indeed within the year critical essays have challenged all previously held concepts of both the form and the function of sensory receptors in the skin of man. It is our purpose to review the field of knowledge concerning the itch sensation in man, to report experimental observations of our own, and to attempt an interpretative analysis of the neurophysiological basis for itching. The modern era of conceptual thinking on the problem of sensory reception in the skin began in 1838, when Johannes Müller1 enunciated his doctrine of specific energy, i. e., he References 1. The open bulla technique of Armstrong et al.65 invariably responds with pain, since it is hyperalgesic. 2. Müller, J.: Handbuch der Physiologie des Menschen , Ed. 2, Coblenz, 1838. 3. Volkmann, A. V.: in Handwörterbuch der Physiologie , edited by R. Wagner, Braunschweig, F. Vreiveg u. Sohn, 1842-1853, Vol. 2. 4. Blix, M.: Experimentelle Beiträge zur Lösung der Frage über die specifische Energie der Hautnerven , ztschr. Biol. , 20:141, 1884. 5. von Frey, M.: Physiologie des Sinnesorgane des menschlichen Haut , Ergebn. Physiol. 9:351, 1910.Crossref 6. Törok, L.: Über das Wesen der Juckempfindung , Ztschr. Psychol. , 46:23, 1907. 7. Titchener, E. B.: A Textbook of Psychology , New York, The Macmillan Company, 1909. 8. Winkler, F.: Studien über das Zustandekommen der Juckempfindung , Arch. Dermat. u. Syph. 99:273, 1910.Crossref 9. von Frey, M.: Zur Physiologie der Juckempfindung , Arch. néerl. physiol. 7:142, 1922. 10. Longo, V.: Sulla topografia della sensibilità del "prurito," Arch. fisiol. 36:197, 1936. 11. Rothman, S.: Beiträge zur Physiologie der Juckempfindung , Arch. Dermat. u. Syph. 139:227, 1922.Crossref 12. Head, H., and others: Studies in Neurology , London, Oxford University Press, 1920, Vol. 2. 13. Gasser, H. S.: Conduction in Nerves in Relation to Fiber Types , A. Research Nerv. & Ment. Dis. Proc. 15:35, 1934. 14. Heinbecker, P.; Bishop, G. H., and O'Leary, J. L.: Analysis of Sensation in Terms of the Nerve Impulse , Arch. Neurol., & Psychiat. 31:34, 1934. 15. Zotterman, Y.: Touch, Pain and Tickling: An Electrophysiological Investigation on Cutaneous Sensory Nerves , J. Physiol. 95:1, 1939. 16. Ranson, S. W.; Droegemueller, W. H.; Davenport, H. K., and Fisher, C.: Number, Size and Myelination of the Sensory Fibers in the Cerebrospinal Nerves , A. Research Nerv. & Ment. Dis. Proc. 15:3, 1934. 17. Lewis, T., and Pochin, E. E.: Double Pain Response of Human Skin to a Single Stimulus , Clin. Sc. 3:67, 1937. 18. Bickford, R. G.: The Fibre Dissociation Produced by Cooling Human Nerves , Clin. Sc. 4:159, 1939. 19. Graham, D. T.; Goodell, H., and Wolff, H. G.: Neural Mechanisms Involved in Itch, "Itchy Skin," and Tickle Sensations , J. Clin. Invest. 30:37, 1951. 20. Goldscheider, A.: Über Irradiation und Hyperästhesie im Bereich der Hautsensibilität. , Arch. ges. Physiol. 165:1, 1916. 21. Bickford, R. G.: Experiments Relating to Itch Sensation, Its Peripheral Mechanism and Central Pathways , Clin. Sc. 3:377, 1938. 22. Rothman, S.: Über die Juckempfindung in ekzematöser Haut , Arch. Dermat. u. Syph. 150:489, 1926. 23. Cormia, F. E.: Experimental Histamine Pruritus: I. Influence of Physical and Psychological Factors on Threshold Reactivity , J. Invest. Dermat. 19:21, 1952. 24. Sonnenschein, R. R.; Cornbleet, T.; Janowitz, H. D., and Grossman, M. I.: Inhibition of "Itchy Skin" with Tetraethylammonium , J. Invest. Dermat. 12:321, 1949. 25. Bishop, G. H.: The Skin as an Organ of Senses with Special Reference to the Itching Sensation , J. Invest. Dermat. 11:143, 1948. 26. Bishop, G. H.: Responses to Electrical Stimulation of Single Sensory Units of the Skin , J. Neurophysiol. 6:361, 1943. 27. Cormia, F. E., and Kuykendall, V.: Experimental Histamine Pruritus: II. Nature, Physical and Environmental Factors Influencing Development and Severity , J. Invest. Dermat. 20:429, 1953. 28. Cormia, F. E., and Kuykendall, V.: Experimental Histamine Pruritus: III. Influence of Drugs on the Itch Threshold , A. M. A. Arch. of Dermat. & Syph. 69:206, 1954. 29. Rajka, E.; Korossy, S., and Gozony, M.: Zur Pathogenese des Urtikariell entzündlichen Juckens , Dermatologica , 112:1, 1956. 30. Kepecs, J. G., and Robin, M.: Studies in Itching , A. M. A. Arch. Neurol. & Psychiat. 76:325, 1956. 31. Magnus, I. A., and Thompson, R. H.: Cholinesterase Levels in the Skin in Cholinogenic Urticaria and Pruritus , Brit. J. Dermat. 68:283, 1956. 32. Shelley, W. B., and Arthur, R. P.: Studies on Cowhage (Mucuna Pruriens) and Its Pruritogenic Proteinase, Mucunain , A. M. A. Arch. Dermat. 72:399, 1955. 33. Arthur, R. P., and Shelley, W. B.: The Role of Proteolytic Enzymes in the Production of Pruritus in Man , J. Invest. Dermat. 25:341, 1955. 34. Ungar, G.: Biochemical Mechanism of the Allergic Reaction , Internat. Arch. Allergy 4:258, 1953. 35. Sinclair, D. C.: Cutaneous Sensation and the Doctrine of Specific Energy , Brain 78:584, 1955. 36. Lele, P. P., and Weddell, G.: The Relationship Between Neurohistology and Corneal Sensibility , Brain , 79:119, 1956. 37. Schiller, F.: The Cutaneous Sensory Modalities: A Critique of Their "Specificity," A. M. A. Arch. Neurol. & Psychiat. 75:203, 1956. 38. Jones, M. H.: Second Pain: Fact or Artifact , Science 124; 442, 1956. 39. Ehrenwald, H., and Königstein, H.: Klinische und experimentelle Untersuchungen über das Juckgefühl , Wien. klin. Wchnschr. 42:1397, 1929. 40. Foerster, O.: Symptomatologic der Erkrankungen des Rückenmarks und seiner Würzeln , in Handbuch der Neurologie , edited by O. Bumke and O. Foerster, Berlin, Springer-Verlag, 1936, Vol. 5, p. 1. 41. McMurray, G. A.: Experimental Study of a Case of Insensitivity to Pain , Arch. Neurol. & Psychiat. 64:650, 1950. 42. Sjöqvist, O.: Studies on Pain Conduction in the Trigeminal Nerve , Acta Psychiat. et Neurol. (Supp. 17) , p. 1, 1938. 43. Hyndman, O. R., and Wolkin, J.: Anterior Cordotomy: Further Observations on Physiologic Results and Optimum Manner of Performance , Arch. Neurol. & Psychiat. 50:129, 1943. 44. Kahn, E. A.: Anterolateral Chordotomy for Intractable Pain , J. A. M. A. 100:1925, 1933. 45. Banzet, P. M.: La Cordotomie, Thesis, Paris, Libraire Louis Arnette, 1927. 46. Sicard, J. A., and Robineau, M.: Cordotomie laterale anterieure pour les algies incurable , Rev. Neurol. 1:21, 1925. 47. White, J. C. and Sweet, W. H.: Pain: Its Mechanisms and Neurosurgical Control , Springfield, Ill., Charles C Thomas, Publisher, 1955. 48. Melton, F. M., and Shelley, W. B.: The Effect of Topical Antipruritic Therapy on Experimentally Induced Pruritus in Man , J. Invest. Dermat. 15:325, 1950. 49. Macintosh, F. C.: Histamine-Releasing Drugs , Ann. Otol. Rhin. & Laryng. 65:385, 1956. 50. Benjamin, F. B.; Beerman, H., and Shelley, W. B.: Allergic Contact Dermatitis Due to Histamine-Releasing Drug 48-80 , A. M. A. Arch. Dermat. 71:190, 1955.Crossref 51. Sigel, H.: Cutaneous Sensory Threshold Stimulation with High Frequency Square-Wave Current: I. The Relationship of Electrode Dimensions to the Sensory Threshold , J. Invest. Dermat. 18:441, 1952. 52. Bishop, G. H.: A Simple Electronic Stimulator Suitable for Peripheral Nerve and Skin Sensory Testing , Electroencephalog. & Clin. Neurophysiol. 5:105, 1953. 53. Lee, R. E.; Williams, H. L., and Pfeiffer, C. C.: A Warm Wire Algesimeter , Fed. Proc. 8:314, 1949. 54. Arthur, R. P., and Shelley, W. B.: Paper in preparation. 55. Shelley, W. B., and Arthur, R. P.: Studies on Pruritus , Tr. A. Am. Physicians 69:285, 1956. 56. Bishop, G. H.: The Structural Identity of the Pain Spot in Human Skin , J. Neurophysiol. 7:185, 1944. 57. Weddell, G.; Palmer, E., and Pallie, W.: Nerve Endings in Mammalian Skin , Biol. Rev. 30:159, 1955. 58. Footnotes deleted on proof. 59. Melton, F. M., and Shelley, W. B.: The Effect of Topical Antipruritic Therapy on Experimentally Induced Pruritus in Man , J. Invest. Dermat. 15:325, 1950. 60. Broadbent, J. L.: Observations on Histamine-Induced Pruritus and Pain , Brit. J. Pharmacol. 10:183, 1955. 61. Shelton, J. M.: Distention Anesthesia for Minor Dermatological Procedures , A. M. A. Arch. Dermat. 75:130, 1957. 62. Nelson, P. G.: Action of Certain Enzymes on the Frog Node of Ranvier , Fed. Proc. 16:93, 1957. 63. West, P. M., and Hilliard, J.: Proteolytic Enzyme Inhibitors of Human Serum in Health and Disease , Proc. Soc. Exper. Biol. & Med. 71:169, 1949. 64. Leimdorfer, A., and Metzner, W. R. T.: Analgesia and Anesthesia Induced by Epinephrine , Am. J. Physiol. 157:116, 1949. 65. Armstrong, D.; Dry, R. M.; Keele, C. A., and Markham, J. W.: Observations on Chemical Excitants of Cutaneous Pain in Man. , J. Physiol. 120:326, 1953. 66. Adrian, E. D.: The Effects of Injury on Mammalian Nerve Fibers , Proc. Roy. Soc. London, (S. B.) 106:596, 1930. 67. Lele, P. P.; Sinclair, D. C., and Weddell, G.: The Reaction Time to Touch , J. Physiol. 123:187, 1954. 68. Landau, W. M. and Bishop, G. H.: Pain from Dermal, Periosteal and Fascial Endings, and from Inflammation , A. M. A. Arch. Neurol. & Psychiat. 69:490, 1953. 69. Ungar, G.: Mechanism of Histamine Release , in the Ciba Foundation Symposium on Histamine , Boston, Little Brown & Co., 1956, p. 431. 70. Magnus, I. A.: Personal communication to the authors, 1955. 71. Cormia, F.: Personal communication to the authors, 1956. 72. Feldberg, W.: On Some Physiological Aspects of Histamine , J. Pharm. & Pharmacol. 6:281, 1954. 73. Bowden, K.; Brown, B. G., and Batty, J. E.: 5-Hydroxytryptamine: Its Occurrence in Cowhage , Nature, London 174:925, 1954. 74. Tower, S. S.: Pain: Definition and Properties of the Unit for Sensory Reception. A. Research Nerv. & Ment. Dis., Proc. 23:16, 1943. 75. Beloff, A., and Peters, R. A.: Observations upon Thermal Burns; Influence of Moderate Temperature Burns upon Proteinase of Skin , J. Physiol. 103:461, 1945. 76. Smith, C. H., and Malkiewicz, G. M.: Role of the Automonic Nervous System in Intense Pruritus Ani , J. Internat. Coll. Surgeons 23:423, 1955. 77. Tomasch, J., and Britton, W. A.: On the Individual Variability of Fiber Composition in Human Peripheral Nerve , J. Anat. 90:337, 1956. 78. Tomasch, J., and Schwarzacher, H. G.: Die Innere Struktur peripherer menschlicher Nerven im Lichte faseranalytischer Untersuchungen , Acta Anat. 16:315, 1952.Crossref 79. 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Journal

A.M.A. Archives of DermatologyAmerican Medical Association

Published: Sep 1, 1957

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