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Neural and vascular regulatory factors of the skin
David A. Walsh,
Giorgio Terenghi,
Julia M. Polak,
Corresponding Author
David A. Walsh
Department of Histochemistry, Royal Postgraduate Medical School, Due Cane-Road, London W12 0NN, England, UK
*Tel: (+44 81) 743 2030, ext. 2151; Fax: (+44 81) 743 5362.Search for more papers by this authorGiorgio Terenghi
Department of Histochemistry, Royal Postgraduate Medical School, Due Cane-Road, London W12 0NN, England, UK
Current address: Blond McIndoe Centre, Queen Victoria Hospital, East Grinstead, Sussex. RH19 3DZ, England, UK.
Search for more papers by this authorJulia M. Polak
Department of Histochemistry, Royal Postgraduate Medical School, Due Cane-Road, London W12 0NN, England, UK
Search for more papers by this authorDavid A. Walsh,
Giorgio Terenghi,
Julia M. Polak,
Corresponding Author
David A. Walsh
Department of Histochemistry, Royal Postgraduate Medical School, Due Cane-Road, London W12 0NN, England, UK
*Tel: (+44 81) 743 2030, ext. 2151; Fax: (+44 81) 743 5362.Search for more papers by this authorGiorgio Terenghi
Department of Histochemistry, Royal Postgraduate Medical School, Due Cane-Road, London W12 0NN, England, UK
Current address: Blond McIndoe Centre, Queen Victoria Hospital, East Grinstead, Sussex. RH19 3DZ, England, UK.
Search for more papers by this authorJulia M. Polak
Department of Histochemistry, Royal Postgraduate Medical School, Due Cane-Road, London W12 0NN, England, UK
Search for more papers by this authorAbstract
Background Neural and vascular factors regulate many aspects of dermal function, including blood flow, inflammation, tissue repair and eccrine secretion. Abnormalities of neurovascular regulation may contribute to dermatological manifestations of a wide range of diseases including psoriasis, nodular prurigo and leprosy, diabetes mellitus and Raynaud's disease.
Aims In this review we discuss evidence for roles played by neural and vascular regulatory factors in skin, with particular reference to the regulatory peptides substance P, calcitonin gene-related peptide. vasoactive intestinal polypeptide, neuropeptide Y and endothelin and to the important endothelial cell product nitric oxide.
Conclusions An understanding of the anatomical basis of neurovascular regulation and the changes which occur during disease may lead to novel diagnostic and prognostic tests for dermatological conditions, while an understanding of specific receptors mediating the actions of regulatory peptides will lead to the development of specific antagonists as a novel approach in clinical dermatology.
References
- 1 Bjorklund H, Dalsgaard CJ, Jonsson CE, Hermansson A. Sensory and autonomic innervation of non-hairy and hairy human skin. Cell Tissue Res 1986; 234: 51–57.
- 2 Wallengren J, Ekman R, Sundler F. Occurrence and distribution of neuropeptides in human skin. An imrnunocytochemical and immunochemical study on normal skin and blister fluid from inflamed skin. Acta Dermatol Vencreol (Stockholm) 1987; 67: 185–192.
- 3 Tainio H, Vaalasti A, Rechardt L. The distribution of substance P, CGRP. Gatanin and ANP-like immunoreactive nerves in human sweat glands. Histochem J 1987; 19: 375–380.
- 4 Hartschuh W, Weihe E, Reinecke M. Peptidergic (neurotensin. VIP, substance P) nerve fibres in the skin. immunohistochemical evidence of an involvement of neuropeptides in nociception, pruritis and inflammation. Br J Dermatol 1983; 109S25: 14–17.
- 5 Tainio H, Vaalastyi A, Rechardt L. The distribution of sympathetic adrenergic, tyrosine hydroxylase and neuropeptide Y-immunoreactive nerves in human axillary sweat glands. Histochemistry 1986; 85: 117–120.
- 6 Hanley MR. Growth factors neuropeptides as mitogens. Nature 1985; 315: 14–15.
- 7 MS O'Doriso, A Panerai (Eds.) Neuropeptides and immunopeptides; messengers in a neuroimmune axis. Ann NY Acad Sci 1990; 594.
- 8 Hartschuh W, Reinecke M, Weihe E, Yanaihara N. VIP-immunoreactivity in the skin of various mammals: immunohistochemical. radioimniunological and experimental evidence for a dual localization in cutaneous nerves and Merkel cells. Peptides 1984; 5: 239–245.
- 9 Foreman J, Jordan C. Histamine release and vascular changes induced by neuropeptides. Agents Actions 1983; 13: 105–116.
- 10 Naura H, Hirose T, Hideaki T, Inayama S, Nakanishi S. Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature 1983; 306: 32–36.
- 11 Karanth SS, Springall DR, Kuhn DM, Levene M.M., Polak JM. An immunocytochemical study of cutaneous innervation and the distribution of neuropeptides and protein gene product 9.5 in man and commonly employed laboratory animals. Am J Anat 1991; 191: 369–383.
- 12 Rees DD, Palmer RM.J., Hodson F, Moncada S. A specific inhibitor of nitric oxide formation from i.-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol 1989; 96: 418–424.
- 13 Cappugi P, Tsampau D, Lotti T. Substance P provokes cutaneous erythema and edema through a histamine-independent pathway. Int J Dermatol 1992; 31: 206–209.
- 14 Lembeck F, Holzer P. Substance P as a neuro-genic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn-Schmiedeberg's Arch Pharmacol 1979; 310: 175–183.
- 15 Lembeck F, Donnerer J, Tsuchiya M, Nagahisa A. The non-peptide tachykinin antagonist. CP-96,345, is a potent inhibitor of neurogenic inflammation. Br J Pharmacol 1992; 105: 527–530.
- 16 Payan DG. Neuropeptides and inflammation: the role of substance P. Ann Rev Med 1989; 40: 341–52.
- 17 Zimmerman BJ, Anderson DC, Granger DN. Neuropetides promote neutrophil adherence to endothelial cell monolayers. Am J Phys 1992; 263: G678–G682.
- 18 Nilsson J, von Euler AM, Dalsgaard CJ. Stimulation of connective tissue cell growth by substance P and substance K. Nature 1985; 315: 61–63.
- 19 Ziche M, Morbidelli L, Pacini M, Geppetli P, Alessandri G, Maggi D-A. Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells. Microvasc Res 1990; 40: 264–278.
- 20 Tanaka T, Danno KI, Ikai K, Imamura S. Effects of substance P and substance K on the growth of cultured keratoinocytes. J invest Dermatol 1988; 90: 399–401.
- 21 Carter RB, Francis WR. Capsaicin desensitization to plasma extravasation evoked by antidromic C-fiber stimulation is not associated with antinociception in the rat. Neurosci Lett 1991; 127: 49–52.
- 22 Lynn B, Ye W, Cotsell B. The actions of capsaicin applied topically to the skin of the rat on C-fibre afferents, antidromic vasodilatation and substance-P levels. Br J Pharmacol 1992; 107: 400–406.
- 23 Bernstein JE, Parish LC, Rapaport M, Rosen-baum, MM, Roenigk HH Jr. Effects of topically applied capsaicin on moderate and severe psoriasis vulgaris. J Am Acad Dermatol 1986; 15: 504–507.
- 24 Tupker RA, Coenraads PJ, van der Mecr JB. Treatment of prurigo nodularis, chronic prurigo and neurodermatitis circumseripta with topical capsaicin. Acta Dermatol Venereol (Stockholm) 1992; 72: 463.
- 25 Takeda Y, Chou KB, Takeda J, Sachais US, Krause JE. Molecular cloning, structural characterization and functional expression of the human substance P receptor. Biochem Biophys Res Commun 1991; 179: 1232–1240.
- 26 Regoli D, Nantel F. Pharmacology of neurokinin receptors. Biopolymers 1991; 3l: 777–783.
- 27 Petitet F, Saffroy M, Torrens Y, Lavielle S, Chassaing G, Loeuillet D, Gowinski J, Beaujouan JC. Possible existence of a new tachykinin receptor subtype in the guinea pig ileum. Peptides 1992; 13: 383–388.
- 28 Jacques L, Couture R, Drapeau G, Regoli D. Capillary permeability induced by intravenous neurokinins. Arch Pharmacol 1989; 340: 170–179.
- 29 Deguchi M, Niwa M, Shigematsu K, Fujii T, Namba K, Ozaki M. Specific 125I. Bolton-Hunter substance P binding sites in human and rat skin. Neurosci Lett 1989; 99(3): 287–292.
- 30 O'Flynn NM, Helme RD, Watkins DJ, Burcher E. Autoradiographic localization of substance P binding sites in rat footpad skin. Neurosci Lett 1989; 106: 43–48.
- 31 Beresford IJM, Birch PJ, Hagan RM, Ireland SJ. Investigation into species variants in tachykinin NK1 receptors by use of the non-peptide antagonist, CP 96.345. Br J Pharmacol 1991; 104: 292–293.
- 32 Amara SG, Jonas V, Rosenfeld MG, Ong ES, Evans RM. Alternative processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature 1982; 198: 240–244.
- 33 Rosenfeld MG, Mermod J-J, Amara SG, Swanson LW, Sawchenko PE, Rivier J, Vale WW, Evans RM. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 1983; 304: 129–135.
- 34 Brain SD, Tippins JR, Morris HR, MacIntyre I, Williams TJ. Potent vasodilator activity of calcitonin gene-related peptide in human skin. J Invest Dermatol 1986; 87: 533–536.
- 35 Gamse R, Saria A. Potentiation of tachykinin-induced plasma protein extravasation by calcitonin gene-related peptide. Eur J Pharmacol 1985; 114: 61–66.
- 36 Brain SD, Williams TJ. Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood How in rat skin. J Pharmacol 1989; 97: 77–82.
- 37 Hegerstrand A, Dalsgaard CJ, Jonzon B, Larsson O, Nilsson J. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells. Proc Natl Acad Sci USA 1990; 87: 3299–3303.
- 38 Abello J, Kaiserlian-Nicolas D, Cuber JC, Revillard JP, Chayvialle JA. Identification of high affinity Calcitonin gene-related peptide receptors on a murine macrophage-like cell. In MS O'Doriso, A Panerai (Eds.). Neuropeptides and immunopeptides: messengers in a neuroimmune axis. Ann NY Acad Sci 1990; 594: 364–366.
- 39 Hosoi J, Murphy GF, Egan CL, Lerner EA, Grabbe S, Asahina A, Granstein RD. Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Nature 1993; 363: 159–161.
- 40 Dennis T, Fournier A, St. Pierre S, Quirion R. Structure-activity profile of calcitonin gene-related peptide peripheral and brain tissues. Evidence for receptor multiplicity. J Pharmacol Exp Ther 1989; 251: 718–725.
- 41 Hughes SR, Brain SD. A calcitonin gene-related peptide (CGRP) antagonist (CGRP8-37) inhibits microvascular responses induced by CGRP and capsaicin in skin. Br J Pharmacol 1991; 104: 738–742.
- 42 Thom N, Hughes AD, Goldberg P, Martin G, Schachter M, Sever PS. The actions of calcitonin gene related peptide and vasoactive intestinal peptide as vasodilators in man in vivo and in vitro. Br J Pharmacol 1987; 24: 139–144.
- 43 Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I. Calcitonin gene-related peptide is a potent vasodilator. Nature 1985; 313: 54–56.
- 44 Gray DW, Marshall I. Nitric oxide synthesis inhibitors attenuate calcitonin gene-related peptide endothelium-dependent vasorelaxation in rat aorta. Eur J Pharmacol 1992; 212: 37–42.
- 45 Greenberg B, Rhoden K, Barnes P. Calcitonin gene-related peptide (CGRP) is a potent non-endothelium-dependent inhibitor of coronary vaso-motor tone. Br J Pharmacol 1987; 92: 789–794.
- 46 Verrecchia C, Hamel E, Edvinsson L, Mackenzie ET, Seylaz J. Role of the endothelium in the pial artery responses to several vasoactive peptides. Acta Physiol Scand 1986; 127(Suppl 552): 33–36.
- 47 Marshall I. Mechanism of vascular relaxation by the calcitonin gene-related peptide, Calcitonin gene-related peptide: the first decade of a novel pleiotropic neuropeptide. Ann NY Acad Sci 1992; 657; 204–215.
- 48 SI Said, (Ed.). Vasoactive Intestinal Peptide. Advances in Peptide Hormone Research Series. New York . Raven Press, 1982.
- 49 Huang M, Rorstad OP. Cerebral vascular adenylate cyclase: evidence for coupling to receptors for vasoactive intestinal peptide and parathyroid hormone. J Neurochem 1984; 43: 849–856.
- 50 Yamashita Y, Ogawa T, Ohnishi N, Imumura R, Sugenoya J. Local effect of vasoactive intestinal polypeptide (VIP) on human sweat-gland function. Jpn J Physiol 1987; 37: 929–936.
- 51 Heggerstrand A, Jonzon B, Dalsgaard C-J, Nilsson J. Vasoactive intestinal polypeptide stimulates cell proliferation and adenylate cyclase activity of cultured human keratinocytes. Proc Natl Acad Sci USA 1989; 86: 5993–5996.
- 52 Wolle U, Knopf B. Vasoactve intestinal peptide (VIP) modulates early events of migration in human keratinocytes. Int J Oncol 1993; 2: 229–232.
- 53 Pincus DW, DiCicco-Bloom EM, Black IB. Vasoactive intestinal peptide regulates mitosis, differentiation and survival of cultured sympathetic neuroblasts. Nature 1990; 343: 564–567.
- 54 Wenger GD, O'Dorisio MS. Vasoactive intestinal peptide: messenger in a neuroimmune axis. In. MS O'Doriso, A Panerai, (Ed). Neuropeptides and immunopeptides: messengers in a neuroimmune axis. Ann NY Acad Sci 1990; 594: 104–106.
- 55 Ishihara T, Shigemoto R, Mori K, Takahashi K, Nagata S. Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Neuron. 1992; 8: 811–819.
- 56 Heinz-Erian P, Paul S, Said SI. Receptors for vasoactive intestinal peptide on isolated human sweat glands. Peptides 1986; 7S1: 151–154.
- 57 Eedy DJ, Shaw C, Armstrong EP, Johnston CF, Buchanan KD. Vasoactive intestinal peptide(VIP) and peptide histidine methionine (PHM) in human eccrine sweat glands; demonstration of innervation, specific binding sites and presence in secretions. Br J Dermatol 1990; 123: 65–76.
- 58 Tatemoto D, Carlquist M, Mutt V, Neuropeptide Y. A novel brain peptide with structural similarities for peptide YY and pancreatic polypeptide. Nature 1982; 296: 659–660.
- 59 JM Allen, JI Koenig, (Eds). Central and peripheral significance of neuropeptide Y and its related peptides. Annals of the New York Academy of Sciences, USA . New York Academy of Sciences. 1990.
- 60 Minth CD, Bloom SR, Polak JM, Dixon JE, Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. Proc Natl Acad Sci USA 1984; 81: 4577–4581.
- 61 Wahlestedt C, Grundemar L, Hakanson R, Heilig M, Shen GH, Zukowska-Grojec Z, Reis DJ. Neuropeptide Y receptor subtypes, Y1 and Y2. Ann NY Acad Sci 1990; 611: 7–26.
- 62 Fuhlendorff J, Gether U, Aaderlund L, Lange-land-Johansen N, Thogersen H, Melberg SG, Olsen UB, Thastrup O, Schwartz TW. Leu31, Pro34 Neuropeptide Y: a specific Y, receptor agonist. Proc Natl Acad Sci USA 1990; 87: 182–186.
- 63 Herzog H, Hurt YJ, Ball HJ, Hayes G, Shine J, Selbie LA. Cloned human neuropeptide Y receptor couples to two different second messenger systems. Proc Natl Acad Sci USA 1992; 89: 5794–5798.
- 64 Larhammar D, Blomqvist AG, Yee F, Jazin E, Yoo H, Wahlestedt C. Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type. J Biol Chem 1992; 267: 10935–10938.
- 65 Jazin EE, Yoo H, Blomqvist AG, Yee F, Weng G, Walker MW, Salon J, Larhammar D, Wahlstedt C. A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, of its human homologue, confers neither NPY binding sites nor NPY responsiveness on transfected cells. Regulat Peptides 1993; 47: 247–258.
- 66 Modin A, Pernow J, Lundberg JM. Evidence for two neuropeptide Y receptors mediating vasoconstriction. Eur J Pharmacol 1991; 203: 165–171.
- 67 Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guilleman R. Hypothalamic peptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973; 179: 77–79.
- 68 Polak JM, Bloom SR. Somatostatin localization in tissues. Scand J Gastroenterol 1986: 21S119: 11–21.
- 69 Blum AM, Metwali A, Mathew RC, Cook G, Elliott D, Weinstock JV. Granuloma T lymphocytes in murine shistosomiatin mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion. J Immunol 1992; 149: 3621–3626.
- 70 Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kohayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothetal cells. Nature 1988: 332: 411–415.
- 71 Bull HA, Bunker CB, Terenghi G, Springall DR, Zhao Y, Polak JM, Dowd PM. Endothelin-1 in human skin: immunolocolisation. receptor binding. mRNA expression, and effects on cutaneous microvascular endothelial cells. J Invest Dermatol 1991; 97: 618–623.
- 72 Brain SD, Crossman DC, Buckley TL, Williams TJ. Endothelin-1: Demonstration of potent effects on the microcirculation of humans and other species. J Cardiovascular Pharmacology 1989; 13(Suppl 5) S147–S149.
- 73 Ishida K, Takeshige K, Minakami S. Endothelin-1 enhances superoxide generation of human neutrophils stimulated by the chemotactic peptide n-formyl-methionyl-leucyl-phenyalanine. Biochem Biophys Res Commun 1990; 173: 496–500.
- 74 Bobik A, Grooms A, Millar JA, Mitchell A, Grinpukel S. Growth factor activity of endothelin on Vascular smooth muscle. Am J Physiol 1990; 258: C408–C415.
- 75 Takuwa N, Takuwa Y, Yanagisawa M, Yamashita K, Masaki T. A novel vasoactive peptide endothelin stimulates mitogenesis through inositol lipid turnover in swiss 3T3 fibroblasts. J Biol Chem 1989: 264: 7856–7861.
- 76 Giaid A, Gibson SJ, Ibrahim NB.N., Legon S, Bloom SR, Yanagisawa M, Masaki T, Varndell IM, Polak JM. Endothelin-1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci USA 1989; 86; 7634–7638.
- 77 Haendler B, Hechter U, Sehleuning WD. Molecular cloning of human endothelin (ET) receptors ET(A) and ET(B). J Cardiovasc Pharmacol 1992; 20: s1–S4.
- 78 Lin HY, Kaji EM, Winkel GK, Kes HE, Lodish HF. Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor. Proc Natl Acad Sci USA 1991; 88: 3185–3189.
- 79 Takayanagi R, Kitazumi K, Takasaki C, Ohnaka K, Aimoto S, Tasaka K, Ohasha M, Nawata H. Presence of non-selective type of endothelin receptor on vascular endothelium and its linkage to vasodilation. FEBS Lett 1991: 282: 103–106.
- 80 Knock GA, Terenghi G, Bunker CB, Bull HA, Dowd PM, Polak JM. Characterizationof endothelin-binding sites in human skin and their regulation in primary Raynaud's phenomenon and systemic sclerosis. J Invest Dermatol 1993; 101 (in press).
- 81 Palmer RM.J., Ferrige AC, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524–526.
- 82 Moncada S, Palmer RM.J., Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991; 43: 119–141.
- 83 Palmer RM.J., Andrews T, Foxwell NA, Moncada S. Glucocorticosteroids do not affect the induction of a novel calcium-dependent nitric oxide synthase in rabbit chondrocytes. Biochem Biophys Res Commun 1992; 188: 209–215.
- 84
Ralevie V,
Khalil Z,
Dusting GJ,
Hulme RD.
Nitric oxide and sensory nerves are involved in the vasodilator response to acetylcholine but not calcitonin gene-related peptide in rat skin microvasculature.
Br J Pharmacol
1992; l06: 650–655.
10.1111/j.1476-5381.1992.tb14390.x Google Scholar
- 86 Toda N, Okamura T. Reciprocal regulation by putatively nitroxidergic and adrenergic nerves of monkey and dog temporal arterial tone. Am J Physiol 1992; 261: 1740–1745.
- 86 Ialenti A, Ianaaro A, Moncada S, Di-Rosa M. Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol 1992; 211: 177–182.
- 87 Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leucocyte adhesion. Proc Natl Acad Sci USA 1991; 88: 4651–4655.
- 88 Frilep JG, Foldes-Filep E, Sirois P. Nitric oxide modulates vascular permeability in the rat coronary circulation. Br J Pharmacol 1993: 108: 323–326.
- 89 Dalsgaard CJ, Rydh M, Haegerstrand A. Cutaneous innervation in man visualised with protein gene product 9.5 (PGP-9.5) antibodies. Histochemistry 1989; 92: 385–389.
- 90 Terenghi G, Sundaresan M, Moscoso G, Polak JM. Neuropeptides and a neuronal marker in cutaneous innervation during human foetal development. J Comp Neurol 1993; 328: 595–603.
- 91 Farber EM, Nickoloff BJ, Recht B, Fraki JE. Stress, symmetry and psoriasis: possible role of neuropeptides. J Am Acad Dermatol 1986; 14: 305–311.
- 92 Naukkarinen A, Nickoloff BJ, Farber EM. Quantification of cutaneous sensory nerves and their substance P content in psoriasis. J Invest Dermatol 1989; 92: 126–129.
- 93 Eedy DJ, Johnston CF, Shaw C, Buchanan KD. Neuropeptides in psoriasis: an immunocytochemical and radioimmunoassay study. J Invest Dermatol 1991; 96: 434–438.
- 94 Johansson O, Han S-W, Enhamre A. Altered cutaneous innervation in psoriatic skin as revealed by PGP-9.5 immunohistiochemistry. Arch Dermatol Res 1991; 283: 519–523.
- 95 Pincelli C, Fantini F, Romualdi P, Sevignani C, Lesa G, Benassi L, Giannetti A. Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured keratinocytes. J Invest Dermatol 1992; 98: 421–427.
- 96 Levy DM, Karanth SS, Springall DR, Polak JM. Depletion of cutaneous nerves and neuropeptides in diabetes mellitus: an immunocytochemical study. Diabetologia 1989; 32: 427–433.
- 97 Levy DM, Terenghi G, Gu X-H, Abraham RR, Springall DR, Polak JM. Immunohistochemical measurements of nerves and neuropeptides in diabetic skin: relationship to tests of neurological function. Diabetologia 1992; 35: 889–897.
- 98 Karanth SS, Springall DR, Francavilla S, Mirrlees DJ, Polak JM. Early increase in CGRP- and VIP-immunoreactive nerves in the skin of streptozo tocin-induced diabetic rats. Histochemistry 1990; 94: 659–666.
- 99 Properzi G, Francavilla S, Poccia G, Aloisi P, Gu X-H, Terenghi G, Polak JM. Early increase precedes a depletion of VIP and PGP-9.5 in the skin of insulin-dependent diabetics: correlation between quantitative immunohistochemistry and clinical assessment of peripheral neuropathy. J Pathol 1992; 169: 269–277.
- 100 Behse F, Buchthal F, Carlsen F, Knappeis GG. Unmyelinated fibres and Schwann cells of sural nerve in neuropathy. Brain 1975; 98: 492–510.
- 111 Takahashi K, Ghatei MA, Lam HC, O'Halloran DJ, Bloom SR. Elevated plasma endothelin in patients with diabetes mellitus. Diabetologia 1990; 33: 306–310.
- 102 Properzi G, Terenghi G, Gu X-H, Poccia G, Pasqua R, Francavilla S, Polak JM. An increase of endothelin-1 immunoreactivity in cutaneous microvessels of early diabetic patients is associated with developing microangiopathy. J Pathol (in press).
- 103 Bunker CB, Terenghi G, Springall DR, Polak JM, Dowd PM. Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon. The Lancet 1990; 336: 1530–1533.
- 104 Terenghi G, Bunker CB, Liu Y-F, Springall DR, Cowen T, Dowd PM, Polak JM. Image analysis quantification of peptide-immunoreacttve nerves in the skin of patients with Raynaud's phenomenon and systemic sclerosis. J Pathol 1991; 164: 245–252.
- 105 Bunker CB, Foreman JC, O'Shaushenessy P, Reavley C, Dowd PM, Calcitonin gene-related peptide in the treatment of severe Raynaud's phenomenon. Br J Dermatol 1989; 121: 43–44.
- 106 Agostoni A, Marasini B, Brondi ML, Bassani C, Cazzaniga A, Botlasso B, Cugno M l-Arginine therapy in Raynaud's phenomenon. Int J Clin Res 1941; 21: 202–203.
- 107 Kahaleh MB. Endothelin, an endothelial-dependent vasoconstrictor in scleroderma. Arth Rheum 1991; 34: 978–983.
- 108 Goldsmith PC, Bunker CB, Leslie TA, Terenghi G, Abadia Molina F, Polak JM, Dowd PM. Cutaneous nerve fibre depletion in vibration white finger. Br J Dermatol 1997: 127: 424.
- 109 Kjartansson J, Dalsgaard C-J, Jonsson C-E. Decreased survival of experimental critical flaps in rats after sensory denervation with capsaicin. Plast Reconstruct Surg 1987; 74: 218–221.
- 110 Adeymo O, Wyhurn GM. Innervation of skin grafts. Transplant Bull 1957; 4: 152–153.
- 111 Hermanson A, Dalsgaard CJ, Bjorklund H, Lindblom U. Sensory reinnervation and sensibility after superficial skin wounds in human patients. Neurosci Lett 1987; 74: 377–382.
- 112 Karanth SS, Dhital S, Springall DR, Polak JM. Reinnervation and neuropeptides in mouse skin flaps. J Autonom Nerv Syst 1990; 31: 127–134.
- 113 Terenghi G, Gu XH, Purkis PE, Polak JM, Leigh I. Morphological changes of neural and vascular peptides in human skin suction blister lesion. Br J Dermatol 1992; 127: 435.
- 114 Manek S, Terenghi G, Shurey C, Nishikawa H, Green CJ, Polak JM. Neovascularisation precedes neural changes in the rat groin skin flap following denervation: an immunohistochemical study. Br J Plastic Surg 1993; 46: 48–55.
- 115 Karanth SS, Springall DR, Lucas S, Levy D, Ashby P, Leven MM, Polak JM. Changes in nerves and neuropeptides in skin from 100 leprosy patients investigated by immunocytochemistry. J Pathol 1989; 157: 15–26.
- 116 Karanth SS, Springall DR, Kar S, Gibson SJ, Royston JP, Banerjeet DK, Polak JM. Time-related decrease of substance P and CGRP in central and peripheral projections of sensory neurones in Mycobacterium leprae infected nude mice: a model for lepromatous leprosy in man. J Pathol 1990; 161: 335–345.
- 117 de Blaquiere GE, Curtis J, Pereira, JH, Turk JL. Denatured muscle grafts for nerve repair in an experimental model of nerve damage in leprosy: part, I - morphometric and functional studies. Int J Leprosy. 1994 (in press).
- 118 Hardaway WA. A case of multiple tumours of the skin accompanied by intense itching. Arch Dermatol 1880; 6: 129.
- 119 Hyde JN, Prurigo nodutaris. In: A. Practical Treatise on Diseases of the Skin for the Use of Students and Practitioners ( JN Hyde, FH Montgomery, Eds.). Philadelphia : Lea and Febiger. 199; 174: 5.
- 120 Johnston JC. A papular persistent dermatosis: report on an undescribed disease. J Cutan Dis 1899; 17: 49.
- 121 Lindley RP, Rowland Payne CME. Neural hyperplasia is not a diagnostic prerequisite in nodular prurigo. J Cutan Pathol 1989; 16: 14–28.
- 122 Vaalasti A, Suomalainen H, Rechardt L. Calcitonin gene-related peptide immunoreactivity in prurigo nodularis: a comparative study with neuro-dermatitis circumscripta. Br J Dermatol 1989; 120: 619–23.
- 123 Abadia Molina F, Burrows NP, Russell Jones R, Terenghi G, Polak JM. Increased sensory neuropeptides in nodular prurigo: a quantitative immunohistochemical analysis. Br J Dermatol 1992; 127: 344–351.
- 124 Ichinose M, Nakajima N, Takahashi T, Yamauchi H, Inoue H, Takishima T. Protection against bradykinin induced bronchoconstriction in athmatic patients by neurokinin receptor antagonist. Lancet 1992; 340: 1248–1251.
- 125 Snider RM, Constantine JW, Lowe JA III, Longo KP, Lebel WS, Woody HA, Drozda SE, Desai MC, Vinick FJ, Spencer RW, Hess HJ. A potent nonpeptide antagonist of the substance P (NK1) receptor. Science 1991; 251: 435–437.
- 126 McLean S, Ganong AH, Seeger TF Bryce DK, Pratt KG, Reynolds LS, Siok CJ, Lowe JA III, Heym J Activity and distribution of binding sites in brain of a nonpeptide substance P(NK1) receptor antagonist. Science 1991; 251: 437–439.
- 127 Morimoto H, Murai M, Maeda Y, Yamaoka M, Nishikawa M, Kiyotoh S, Fujii T. FK224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity. J Pharmacol Exp Ther 1992; 224: 398–402.
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