Sympathetic nervous system and neurotransmitters: their possible role in neuroimmunomodulation of multiple sclerosis and some other autoimmune diseases
Multiple sclerosis is still a disease without a cure. Although intensive research efforts have led to the development of drugs that modify the activity of the disease, most of them have various side effects and are expensive. At the same time it is becoming apparent that some remedies usually used to treat somatic and psychic disorders also have immunomodulating properties, and may help manage multiple sclerosis and other autoimmune diseases. We describe here the role of the sympathetic nervous system in the neuro-immune interaction in multiple sclerosis and other immune diseases with increased cellular immunity as well as neurochemical disturbances that take place in these disorders.
- Kazan Rehabilitation Medical Health Center “Sanatorium Krutushka”, 420130, Kazan, Russia
-  S.Y. Felten, D.L. Felten, D.L. Bellinger, S.L. Carlson, K.D. Ackerman, K.S. Madden, J.A. Ol-schowka and S. Livnat: “Noradrenergic sympathetic innervation of lymphoid organs”, Prog. Allergy., Vol. 43, (1988), pp. 14–36.
-  K.S. Madden, V.M. Sanders and D.L. Felten: “Catecholamine influences and sympathetic neural modulation of immune responsiveness”, Annu. Rev. Pharmacol. Toxicol., Vol. 35, (1995), pp. 417–448. [Crossref]
-  A.B. Dahlstro and B.E.M. Zetterstrom: “Noradrenaline stores in nerve terminals of the spleen: changes during hemorrhagic shock”, Science (Wash DC), Vol. 147, (1965), pp. 1583–1585. [Crossref]
-  B.E. Zetterstrom, T. Hokfelt, K.A. Norberg and P. Olsson: “Possibilities of a direct adrenergic influence on blood elements in the dog spleen”, Acta Chir. Scand., Vol. 139, (1973), pp. 117–122.
-  F.D. Reilly, R.S. McCuskey and H.A. Meineke: “Studies of the hemopoietic microenvironment. VIII. Andrenergic and cholinergic innervation of the murine spleen”, Anat. Rec., Vol. 185, (1976), pp. 109–117.
-  F.D. Reilly, P.A. McCuskey, M.L. Miller, R.S. McCuskey and H.A. Meineke: “Innervation of the periarteriolar lymphatic sheath of the spleen”, Tissue Cell, Vol. 11, (1979), pp. 121–126.
-  M.G. Blennerhassett and J. Bienenstock: “Sympathetic nerve contact causes maturation of mast cells in vitro”, J. Neurobiol., Vol. 35, (1998), pp. 173–182. [Crossref]
-  A.S. Maisel, T. Harris, C.A. Rearden and M.C. Michel: “Beta-adrenergic receptors in lymphocyte subsets after exercise. Alterations in normal individuals and pa-tients with congestive heart failure”, Circulation, Vol. 2, (1990), pp. 2003–2010. [Crossref]
-  M.M. Khan, P. Sansoni, E.D. Silverman, E.G. Engleman and K.L. Melmon: “Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes”, Biochem. Pharmacol., Vol. 35, (1986), pp. 1137–1142. [Crossref]
-  Z. Zidek: “Adenosine-cyclic AMP pathways and cytokine expression”, Eur. Cytokine Netw., Vol. 10, (1999), pp. 319–328. [PubMed]
-  I.J. Elenkov, G. Hasko, K.J. Kovacs and E.S. Vizi: “Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha production by selective alpha-and betaadrenergic drugs in mice”, J. Neuroimmunol., Vol. 61, (1995), pp. 123–131. [Crossref]
-  I.J. Elenkov, D.A. Papanicolaou, R.L. Wilder and G.P. Chrousos: “Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications”, Proc. Assoc. Am. Physicians, Vol. 108, (1996), pp. 374–381.
-  I.J. Elenkov, E. Webster, D.A. Papanicolaou, T.A. Fleisher, G.P. Chrousos and R.L. Wilder: “Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors”, J. Immunol., Vol. 161, (1998), pp. 2586–2593.
-  T.C. van der Pouw Kraan, L.C. Boeije, R.J. Smeenk, J. Wijdenes and L.A. Aarden: “Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production”, J. Exp. Med., Vol. 181, (1995), pp. 775–779.
-  G. Hasko, C. Szabo, Z.H. Nemeth, V. Kvetan, S.M. Pastores, E.S. Vizi: “Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide productionin RAW 264.7 macrophages and in endotoxemic mice”, J. Immunol., Vol. 157, (1996), pp. 4634–4640.
-  A.A. Link, T. Kino, J.A. Worth, J.L. McGuire, M.L. Crane, G.P. Chrousos, R.L. Wilder and I.J. Elenkov: “Ligand-activation of the adenosine A2a receptors inhibits IL-12 production by human monocytes”, J. Immunol., Vol. 164, (2000), pp. 436–442. [Crossref]
-  M.M. Bartik, W.H. Brooks and T.L. Roszman: “Modulation of T cell proliferation by stimulation of the beta-adrenergic receptor: lack of correlation between inhibition of T cell proliferation and cAMP accumulation”, Cell. Immunol., Vol. 148, (1993), pp. 408–421. [Crossref]
-  P. Panina-Bordignon, D. Mazzeo, P.D. Lucia, D. D’Ambrosio, R. Lang, L. Fabbri, C. Self and F. Sinigaglia: “Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12”, J. Clin. Invest., Vol. 100, (1997), pp. 1513–1519. [Crossref]
-  G. Hasko, Z.H. Nemeth, C. Szabo, G. Zsilla, A.L. Salzman and E.S. Vizi: “Isoproterenol inhibits Il-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages”, Brain Res. Bull., Vol. 45, (1998), pp. 183–187. [Crossref]
-  R.T. Johnson: “The virology of demyelinating diseases”, Ann. Neurol., Vol. 36 (Suppl.), (1994), pp. S54–60.
-  S.S. Soldan, T.P. Leist, K.N. Juhng, H.F. Mc-Farland and S. Jacobson: “Increased lymphoproliferative response to human herpesvirus type 6A variant in multiple sclerosis patients”, Ann. Neurol., Vol. 47, (2000), pp. 306–313.
-  S.S. Soldan and S. Jacobson: “Role of viruses in etiology and pathogenesis of multiple sclerosis”, Adv. Virus Res., Vol. 56, (2001), pp. 517–555. [Crossref]
-  K.P. Wandinger, W. Jabs, A. Siekhaus, S. Bubel and P. Trillenberg: “Association between clinical disease activity and Epstein-Barr virus reactivation in MS”, Neurology, Vol. 55, (2000), pp. 178–184. [Crossref]
-  C.N. Martyn, M. Cruddas, D.A. Compston: “Symptomatic Epstein-Barr virus infection and multiple sclerosis”, J. Neurol. Neurosurg. Psychiatry, Vol. 56, (1993), pp. 167–168. [Crossref]
-  S. Sriram, W. Mitchell and C. Stratton: “Multiple sclerosis associated with Chlamydia pneumoniae infection of the CNS”, Neurology, Vol. 50, (1998), pp. 571–572. [Crossref]
-  S. Sriram, C.W. Stratton, S. Yao, A. Tharp and L. Ding: “Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis”, Ann. Neurol., Vol. 46, (1999), pp. 6–14.
-  E. Maida: “Immunological reactions against Mycoplasma pneumoniae in multiple sclerosis: preliminary findings”, J. Neurol., Vol. 229, (1983), pp. 103–111. [Crossref]
-  D.A. Dyment, G.C. Ebers and A.D. Sadovnick: “Genetics of multiple sclerosis”, Lancet Neurol., Vol. 3, (2004), pp. 104–110. [Crossref]
-  J.L. Haines, Y. Bradford, M.E. Garcia and A.D. Reed, E. Neumeister: “Multiple susceptibility loci for multiple sclerosis”, Hum. Mol. Genet., Vol. 11, (2002), pp. 2251–2256.
-  U. Christen, D. Benke, T. Wolfe, E. Rodrigo, A. Rhode, A.C. Hughes and M.B. Oldstone: “Cure of prediabetic mice by viral infections involves lymphocyte recruitment along an IP-10 gradient”, J. Clin. Invest., Vol. 113, (2004), pp. 74–84. [Crossref]
-  U. Christen and M.G. Von Herrath: “Infections and autoimmunity - good or bad?”, J. Immunol., Vol. 174, (2005), pp. 7481–7486. [Crossref]
-  P.D. Katsikis, S.B. Cohen, M. Londei and M. Feldman: “Are CD4+ Th1 cells proin-flammatory or anti-inflammatory? The ratio of IL-10 to INF-gamma or IL-2 determines their function”, Int. Immunol., Vol. 7, (1995), pp. 1287–1294.
-  P.B. Carrieri, V. Provitera, T. De Rosa, G. Tartaglia, F. Gorga and O. Perrella: “Profile of cerebrospinal fluid and serum cytokines in patients with relapsing-remitting multiple sclerosis: a correlation with clinical of IRS activation, such as T cell activation increased activity”, Immunopharmacol. Immunotoxicol., Vol. 20, (1998), pp. 373–382. http://dx.doi.org/10.3109/08923979809034820[Crossref]
-  P. Hautecoeur, G. Forzy, P. Gallois, V. Demirbilek and O. Feugas: “Variations of IL2, IL6, TNF alpha plasmatic levels in relapsing remitting multiple sclerosis”, Acta Neurol. Belg., Vol. 97, (1997), pp. 240–243.
-  O. Mikova, R. Yakimova, E. Bosmans, G. Kenis and M. Maes: “Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis”, Eur. Neuropsychopharmacol., Vol. 11, (2001), pp. 203–208. [Crossref]
-  R.L. Wilder: “Neuroendocrine-immune system interactions and autoimmunity”, Annu. Rev. Immunol., Vol. 13. (1995), pp. 307–338. [Crossref]
-  J.W. Karaszewski, A.T. Reder, R. Maselli, M. Brown and B.G. Arnason: “Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis”, Ann. Neurol., Vol. 27, (1990), pp. 366–372.
-  E. Chelmicka-Schorr, M.N. Kwasniewski, B.E. Thomas and B.G. Arnason: “The beta-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats”, J. Neuroimmunol., Vol. 25, (1989), pp. 203–207. [Crossref]
-  K. Wiegmann, S. Muthyala, D.H. Kim, B.G. Arnason and E. Chelmicka-Schorr: “Beta-adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats”, J. Neuroimmunol., Vol. 56, (1995), pp. 201–206. [Crossref]
-  S.E. Ross, R.O. Williams, L.J. Mason, C. Mauri, L. Marinova-Mutafchieva, A.M. Malfait, R.N. Maini and M. Feldmann: “Suppression of TNF-alpha expression, inhibition of Th1 activity, and amelioration of collagen-induced arthritis by rolipram”, J. Immunol., Vol. 159, (1997), pp. 6253–6259.
-  L. Liang, E. Beshay and G.J. Prud’homme: “The phosphodiesterase inhibitors pentoxifylline and rolipram prevent diabetes in NOD mice”, Diabetes, Vol. 47, (1998), pp. 570–575. [Crossref]
-  W.B. Essmann: “Serotonin distribution in tissue and fluids”, In: W.B. Essmann (Ed.): Serotonin in health and disease, Vol. 1, Spectrum, New York.
-  T.M. Aune, K.M. McGrath, T. Sarr, Bombara and K.A. Kelley: “Expression of 5HT1a receptors on activated human T cells”, J. Immunol., Vol. 151, (1993), pp. 1175–1183.
-  M.R.I. Young, J.L. Kut, M.P. Coogan, M.A. Wright, M.E. Young and J. Matthews: “Stimulation of splenic T-lymphocyte function by endgenuous serotonin and by low-dose exogenous serotonin”, Immunology, Vol. 80, (1993), pp. 395–400.
-  M.R.I. Young and J.P. Matthews: “Serotonin regulation of T-cell subpopulations and of macro-phage accessory function”, Immunology, Vol. 84, (1995), pp. 148–152.
-  M. Freire-Garabal, M.J. Nunez, J. Balboa, P. Lopez-Delgado, R. Gallego, T. Garcia-Caballero, M.D. Fernandez-Roel, J. Brenlla and M. Rey-Mendez: “Serotonin upregulates the activity of phagocytosis through 5-HT1A receptors”, Br. J. Pharmacol., Vol. 139, (2003), pp. 457–463.
-  T.M. Aune, H.W. Golden and K.M. McGrath: “Inhibitors of serotonin synthesis and antagonists of serotonin 1A receptors inhibit T lymphocyte function in vitro and cell-mediated immunity in vivo”, J. Immunol., Vol. 153, (1994), pp. 489–498.
-  D. Davidson, I.A. Pullar, C. Mawdsley, N. Kinloch and C.M. Yates: “Monoamine metabolites in cerebrospinal fluid in multiple sclerosis”, J. Neurol. Neurosur. Psychiatry, Vol. 40, (1977), pp. 741–745. [Crossref]
-  B. Johansson and B.E. Ross: “5-hydroxyindoleacetic acid and homovanillic acid in CSF of patients with neurological disease”, Eur. Neurol., Vol. 11, (1977), pp. 37–45.
-  V. Sonnien, P. Riekkinen and U.K. Rinne: “Acid monoamine metabolites in cerebrospinal fluid in multiple sclerosis”, Neurology, Vol. 23, (1973), pp. 760–763. [Crossref]
-  J.E. Blalock: “The syntax of immune-neuroendocrine communication”, Immunol. Today, Vol. 15, (1994), pp. 504–511.
-  W. Savino, E. Arzt and M. Dardenne: “Immunoneuroendocrine connectivity: the paradigm of the thymus-hypothalamus-pituitary axis”, Neuroimmunomodulation, Vol. 6, (1999), pp. 126–136. [Crossref]
-  O.J.G. Schiepers, M.C. Wichers and M. Maes: “Cytokines and major depression”, Prog. Neuro-Psychopharmacol. Biol. Psychiatry, Vol. 29, (2005), pp. 201–217.
-  M. Maes, R. Verkerk, S. Bonaccorso, W. Ombelet, E. Bosmans and S. Scharpe: “Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation”, Life Sci., Vol. 71, (2002), pp. 1837–1848. [Crossref]
-  M. Wichers and M. Maes: “The role of indoleamine 2,3 dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression”, J. Psychiatry. Neurosci., Vol. 29, (2004), pp. 11–17.
-  A. Mangoni: “The kynurenine shunt and depression”, Adv. Biochem. Psychopharmacol., Vol. 11, (1974), pp. 293–298.
-  J.J.A. Hendriks, C.E. Teunissen, H.E. de Vries and C.D. Dijkstra: “Macrophages and neurodegeneration”, Brain Res. Rev., Vol. 48, (2005), pp. 185–195. [Crossref]
-  M. Salter and C.I. Pogson: “The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes”, Biochem. J., Vol. 229, (1985), pp. 499–504.
-  J.M. Loftis and P. Hauser: “The phenomenology and treatment of interferon-induced depression”, J. Affect. Disord., Vol. 82, (2004), pp. 175–90. [Crossref]
-  A. Amirkhani, C. Rajda, B. Arvidsson, K. Bencsik, K. Boda, E. Seres, K.E. Markides, L. Vecsei and J. Bergquist: “Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients”, Eur. J. Neurol., Vol. 12, (2005), pp. 625–631. [Crossref]
-  Z. Hartai, P. Klivenyi, T. Janaky, B. Penke, L. Dux and L. Vecsei: “Kynurenine metabolism in multiple sclerosis”, Acta Neurol. Scand., Vol. 112, (2005), pp. 93–96. [Crossref]
-  E. Kwidzinski, J. Bunse, O. Aktas, D. Richter, L. Mutlu, F. Zipp, R. Nitsch and I. Bechmann: “Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation”, FASEB J., Vol. 19, (2005), pp. 1347–1349.
-  F.E. Bloom, J. Rossier, E.L.F. Battenberg, A. Bayon, E. French, S.J. Hendriksen, G.R. Siggins, D. Segal, R. Browne, N. Ling and R. Guillemin: “Beta endorphin: cellular localization, electrophysiological and behavioral effects”, Adv. Biochem. Psychopharmacol., Vol. 18, (1978), pp. 89–109.
-  L.G. Roda, L. Bongiorno, E. Trani, A. Urbani and M. Marini: “Positive and negative immunomodulation by opioid peptides”, Int. J. Immunopharmacol., Vol. 18, (1996), pp. 1–16. [Crossref]
-  A. Kavelaars, R.E. Ballieux and C.J. Heijnen: Differential effects of beta-endorphin on cAMP levels in human peripheral blood mononuclear cells”, Brain Behav. Immun., Vol. 4, (1990), pp. 171–179. [Crossref]
-  R. Przewlocki, A.H. Hassan, W. Lason, C. Epplen, A. Herz, C. Stein: “Gene expression and localization of opioid peptides in immune cells of inflamed tissue: functional role in antinociception”, Neuroscience, Vol. 48, (1992), pp. 491–500. [Crossref]
-  J.E. Blalock: “A molecular basis for bidirectional communication between the immune and neuroendocrine systems”, Physiol. Rev., Vol. 69, (1989), pp. 1–32.
-  M. Gironi, V. Martinelli and E. Brambilla: “Beta-endorphin concentrations in peripheral blood mononuclear cells of patients with multiple sclerosis”, Arch. Neurol., Vol. 57, (2000), pp. 1178–1181. [Crossref]
-  M. Gironi, R. Furlan, M. Rovaris, G. Comi, M. Filippi, A.E. Panerai and P. Sacerdote: “ß endorphin concentrations in PBMC of patients with different clinical phenotypes of multiple sclerosis”, J. Neurol. Neurosurg. Psychiatry, Vol. 74, (2003), pp. 495–497. [Crossref]
-  P. Sacerdote, B. Manfredi and L. Gaspani: “The opioid antagonist naloxone induces a shift from type 2 to type 1 cytokine pattern in BALB/cJ mice”, Blood, Vol. 95, (2000), pp. 2031–2036.
-  J. Hosoi, H. Ozawa, R.D. Granstein: “Beta-endorphin binding and regulation of cytokine expression in Langerhans cells”, Ann. N.Y. Acad. Sci., Vol. 885, (1999), pp. 405–413. http://dx.doi.org/10.1111/j.1749-6632.1999.tb08700.x[Crossref]
-  D.R. Smith, K.E. Balashov, D.A. Hafler, S.J. Khoury and H.I. Weiner: “Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: increased interleukin-4 production and associated eosinophilia”, Ann. Neurol., Vol. 42, (1997), pp. 313–318.
-  H.C. Nousari, A.K. Asadi and F.A. Tausk: “Subacute cutaneous lupus erythomatosus associated with interferon beta 1a”, Lancet, Vol. 352, (1998), pp. 1825–1826.
-  Y. Kreiss, O. Cohen, E. Pras and A. Achiron: “Subacute thyroiditis in a patient with multiple sclerosis treated with interferon beta 1a”, Neurology, Vol. 53, (1999), pp. 1606–1611.
-  M. Rotondi, G. Mazziotti, B. Biondi, G. Mangallena, A.D. Del Buono and P. Montella: “Long term treatment with interferon beta therapy for multiple sclerosis and occurrence of graves disease”, J. Endocrinol. Invest., Vol. 23, (2000), pp. 321–324. [Crossref]
-  J.L. Goeb, C. Even, G. Nicolas, B. Gohier, F. Dubas and J.B. Garre: “Psychiatric side effects of interferon-beta in multiple sclerosis”, Eur. Psychiatry, Vol. 21, (2006), pp. 186–193. [Crossref]
-  W. Haymaker: Bing’s local diagnosis in neurological diseases, The C.V. Mosby Company, Saint Louis, 1969.
-  R. Sandyk: “Demyelination as an epiphenomenon in multiple sclerosis”, Int. J. Neurosci., Vol. 72, (1993), pp. 141–148.
-  D.S. Russel: “Trauma and multiple sclerosis”, Lancet, Vol. 1, (1964), p. 978. [Crossref]
-  N.R. Ghatak, A. Hirano, H. Lijtmaer and H.M. Zimmerman: “Asymptomatic demyelinated plaque in the spinal cord”, Arch. Neurol., Vol. 30, (1974), pp. 484–486. [Crossref]
-  J.G. Phadke and P.V. Best: “A typical and clinically silent multiple sclerosis: a report of 12 cases discovered unexpectedly at necropsy”, J. Neurol. Neurosurg. Psychiatry, Vol. 46, (1983), pp. 414–420. http://dx.doi.org/10.1136/jnnp.46.5.414[Crossref]
-  S.G. Lynch, J.W. Rose, W. Smoker and J.H. Petajan: “MRL in familial multiple sclerosis”, Neurology, Vol. 40, (1990), pp. 900–903. [Crossref]
-  A.L. Traboulsee and D.K. Li: “The role of MRI in the diagnosis of multiple sclerosis”, Adv. Neurol., Vol. 98, (2006), pp. 125–146.
-  A. Theodoridou and L. Settas: “Demyelination in rheumatic diseases”, J. Neurol. Neurosurg. Psychiatry, Vol. 77, (2006), pp. 290–295.
-  A. Geissler, T. Andus and M. Roth: “Focal white-matter lesions in brain of patients with inflammatory bowel disease”, Lancet, Vol. 345, (1995), pp. 897–898.
-  P. Whiting, R. Harbord, C. Main, J.J. Deeks, G. Filippini, M. Egger and J.A.C. Sterne: “Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review”, Br. Med. J., Vol. 332, (2006), pp. 875–884. [Crossref]
-  M.T. Hyyppa, T. Jolma, P. Riekkinen and U.K. Rinne: “Effects of L-tryptophan on central indoleamine metabolism and short-lasting neurologic disturbances in multiple sclerosis”, J. Neural. Transm., Vol. 37, (1975), pp. 297–304. [Crossref]
-  R.T. Joffe: “Depression and multiple sclerosis: a potential way to understand the biology of major depressive illness”, J. Psychiatry Neurosci., Vol. 30, (2005), pp. 9–10.
-  D.C. Mohr, D.E. Goodkin, J. Islar, L. Hauser and C.P. Genain: “Treatment of depression is associated with suppression of nonspecific and antigen-specific Th1 responses in multiple sclerosis”, Arch. Neurol., Vol. 58, (2001), pp. 1081–1086. [Crossref]
-  D.C. Mohr, L. Stacey, A. Hart and A. Golberg: “Effects of treatment for depression on fatigue in multiple sclerosis”, Psychosom. Med., Vol. 65, (2003), pp. 542–547.
-  S. Hart, I. Fonareva, N. Merluzzi and D.C. Mohr: “Treatment for depression and its relationship to improvement in quality of life and psychological well-being in multiple sclerosis patients”, Qual. Life Res., Vol. 14, (2005), pp. 695–703. [Crossref]
-  A.C. Jung, T. Staiger and M. Sullivan: “The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain”, J. Gen. Intern. Med., Vol. 12, (1997), pp. 384–389. [Crossref]
-  E.N. Duman, M. Kesim, M. Kadioglu, E. Yaris, N.I. Kalyoncu and N. Erciyes: “Possible involvement of opioidergic and serotonergic mechanisms in antinociceptive effect of paroxetine in acute pain”, J. Pharmacol. Sci., Vol. 94, (2004), pp. 161–165. [Crossref]
-  M. Kesim, E.N. Duman, M. Kadioglu, E. Yaris, N.I. Kalyoncu, N. Erciyes: “The different roles of 5-HT(2) and 5-HT(3) receptors on antinociceptive effect of paroxetine in chemical stimuli in mice”, J. Pharmacol. Sci., Vol. 97, (2005), pp. 61–66. [Crossref]
-  F. Lechin, B. van der Dijs and M.E. Lechin (Ed.): Neurocircuitry and Neuroautonomic Disorders: Reviews and Therapeutic Strategies, Karger, Basel, 2002.
-  F. Lechin, B. van der Dijs and A.E. Lechin: “Treatment of bronchial asthma with tianeptine”, Methods Find. Exp. Clin. Pharmacol., Vol. 26, (2004), pp. 697–701. [Crossref]
-  F. Lechin, B. van der Dijs, B. Orozco, E. Jahn, S. Rodriguez and S. Baez: “Neuropharmacological treatment of refractory idiopathic thrombocytopenic purpura: roles of circulating catecholamines and serotonin”, Thromb. Haemost., Vol. 91, (2004), pp. 1254–1256.
-  F. Lechin and B. van der Dijs: “Neuropharmacological therapy of carcinoid syndrome”, Neuroendocrinology, Vol. 81, (2005), pp. 137–138. [Crossref]
-  F. Lechin, B. van der Dijs, B. Orozco, G. Hernandez-Adrian, S. Rodriguez and S. Baez: “Similar autonomic nervous system disorders underlying cystic fibrosis and pancreatic cysts allowed common neuropharmacological therapy: Report of four cases”, J. Appl. Res., Vol. 5, (2005b), pp. 299–304.
-  F. Lechin, B. van der Dijs, B. Orozco, S. Rodriguez and S. Baez: “Neuropharmacological therapy of polycythemia vera: roles of circulating catecholamines and serotonin”, Thromb. Hemost., Vol. 93, (2005), pp. 175–177.
-  T.C. Birdsall: “5-Hydroxytryptophan: a clinically-effective serotonin precursor”, Altern. Med. Rev., Vol. 3, (1998), pp. 271–280.
-  E.H. Turner and A.D. Blackwell: “5-Hydroxytryptophan plus SSRIs for interferoninduced depression: Synergistic mechanisms for normalizing synaptic serotonin”, Med. Hypoth., Vol. 65, (2005), pp. 138–144. [Crossref]
-  E.H. Turner, J.M. Loftis and A.D. Blackwell: “Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan”, Pharmacol. Ther., Vol. 109, (2005), pp. 325–338.
-  M. Kubera, A. Lin, G. Kenis, E. Bosmans, D. van Bockstaele and M. Maes: “Anti-inflammatory effects of antidepressants through suppression of the interferongamma/interleukin-10 production ratio”, J. Clin. Psychopharmacol., Vol. 21, (2001), pp. 199–206. [Crossref]
-  M. Kubera, G. Kenis, E. Bosmans, S. Scharpe and M. Maes: “Effects of serotonin and serotonergic agonists and antagonists on the production of interferon-g and interleukin-10”, Neuropsychopharmacology, Vol. 23, (2000), pp. 89–98. [Crossref]
-  M. Maes, C. Song, A.-H. Lin, S. Bonaccorso and G. Kenis: “Negative immunoregulatory effects of antidepressants: inhibition of interferon-g and stimulation of interleukin-10 secretion”, Neuropsychopharmacology, Vol. 20, (1999), pp. 370–379.
-  M. Maes: “The immunoregulatory effects of antidepressants”, Hum. Psychopharmacol., Vol. 16, (2001), pp. 95–103. [Crossref]
-  M. Maes, G. Kenis and M. Kubera: “The negative immunoregulatory effects of fluoxetine in relation to the camp-dependent PKA pathway”, Int. Immunopharmacol., Vol. 5, (2005), pp. 609–618. [Crossref]
-  H. Iwata, H. Okamoto and S. Ko: “Effects of various drugs on serum free and total tryptophan levels and brain tryptophan metabolism in rats”, Jpn. J. Pharmacol., Vol. 25, (1975), pp. 303–310.
-  A.A. Badawy: “Mechanisms of elevation of rat brain tryptophan concentration by various doses of salicylate”, Br. J. Pharmacol., Vol. 76, (1982), pp. 211–213.
-  A. Groppetti, P.C. Braga, G. Biella, M. Parenti, L. Rusconi and P. Mantegazza: “Effect of aspirin on serotonin and metenkephalin in brain: correlation with the antinociceptive activity of the drug”, Neuropharmacology, Vol. 27, (1988), pp. 499–505. [Crossref]
-  M. Sandrini, G. Vitale and L.A. Pini: “Central antinociceptive activity of acetylsalicylic acid is modulated by brain serotonin receptor subtypes”, Pharmacology, Vol. 65, (2002), pp. 193–197. [Crossref]
-  K. Schroecksnadel, C. Winkler, B. Wirleitner, H. Schennach and D. Fuchs: “Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro”, Clin. Exp. Immunol., Vol. 140, (2005), pp. 41–45. [Crossref]
-  D. Martinez, A. Broft and M. Laruelle: “Pindolol augmentation of antidepressant treatment: recent contributions from brain imaging studies”, Biol. Psychiatry, Vol. 48, (2000), pp. 844–853. [Crossref]
-  E.B. Perry, R.M. Berman, G. Sanacora, A. Anand, K. Lynch-Colonese and D.S. Charney: “Pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitors: a double-blind, randomized, controlled trial”, J. Clin. Psychiatry, Vol. 65, (2004), pp. 238–243. http://dx.doi.org/10.4088/JCP.v65n0215[Crossref]
-  C.F. Scott Jr, N. Cashman and L.E. Spitler: “Experimental allergic encephalitis; treatment with drugs which alter CNS serotonin levels”, J. Immunopharmacol., Vol. 4, (1982-83), pp. 153–162. [Crossref]
-  M. Freire-Garabal, M.J. Nunez, J. Balboa, L.A. Garci, S. Argibay, E. Rodrigo and M. Rey-Mendez: “Administration of the 5-hydroxytryptamine(1A) receptor antagonist WAY100635 suppresses acute experimental allergic encephalomyelitis in Lewis rats”, Neurosci. Lett., Vol. 342, (2003), pp. 33–36.
-  H.H. Hofstetter, R. Mossner, K.P. Lesch, R.A. Linker, K.V. Toyka and R. Gold: “Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE”, Clin. Exp. Immunol., Vol. 142, (2005), pp. 39–44. [Crossref]
-  F. Lechin, B. van der Dijs, G. Hernandez-Adrian: “Dorsal raphe vs. median raphe serotonergic antagonism. Anatomical, physiological, behavioral, neuroendocrinological, neuropharmacological and clinical evidences: Relevance for neuropharmacological therapy”, Prog. Neuropsychopharmacol. Biol. Psychiatry, Vol. 30, (2006), pp. 565–585. [Crossref]
-  S.S. Mosko and B.L. Jacobs: “Midbrain raphe neurons: sensitivity to glucocorticoids and ACTH in the rat”, Brain Res., Vol. (89), (1975), pp. 368–375.
-  G. Bagdy, A.E. Calogero, K. Szemeredi, M.T. Gomez, D.L. Murphy and G.P. Chrousos: “Beta-endorphin responses to different serotonin agonists: involvement of corticotropin-releasing hormone, vasopresin, and direct pituitary action”, Brain Res., Vol. 537, (1990), pp. 227–232.
-  N. Laaris, E. Le Poul, M. Hamon and L. Lanfumey: “Stress-induced alterations of somatodendritic 5-HT1A autoreceptor sensitivity in the rat dorsal raphe nucleus - in vitro electrophysiological evidence”, Fundam. Clin. Pharmacol., Vol. 11, (1997), pp. 206–214. http://dx.doi.org/10.1111/j.1472-8206.1997.tb00187.x[Crossref]
-  I. Huitinga, Z.A. Erkut, D. van Beurden and D.F. Swaab: “Impaired hypothalamuspituitary-adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions”, Ann. Neurol., Vol. 55, (2004), pp. 37–45.
-  S.E. Drewes, J. George and F. Khan: “Recent findings on natural products with erectile-dysfunction activity”, Phytochemistry, Vol. 62, (2003), pp. 1019–1025. [Crossref]
-  A.T. Guay, R.F. Spark and J. Jacobson: “Yohimbine treatment of organic erectile dysfunction in a dose-escalation trial”, Int. J. Impot. Res., Vol. 14, (2002), pp. 25–31. [Crossref]
-  J.M. Baraban and G.K. Aghajanian: “Noradrenergic innervation of serotonergic neurons in the dorsal raphe: demonstration by electron microscopic autoradiography”, Brain Res., Vol. 204, (1981), pp. 1–11. [Crossref]
-  L. Ferraro, K. Fuxe, S. Tanganelli, M. Fernandez, F.A. Rambert and T. Antonelli: “Amplification of cortical serotonin release: a further neurochemical action of the vigilance-promoting drug modafinil”, Neuropharmacology, Vol. 39, (2000), pp. 1974–1983. [Crossref]
-  S Caccia: “Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications”, Clin. Pharmacokinet. Vol. 34, (1998), pp. 281–302. [Crossref]
-  B.S. McEwen and S. Chattarji: “Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine”, Eur. Neuropsychopharmacol., Vol. 14 (Suppl 5), (2004), pp. S497–502. [Crossref]
-  W. Binder, S.A. Mousa, N. Sitte, M. Kaiser, C. Stein and M. Schafer: “Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue”, Eur. J. Neurosci., Vol. 20, (2004), pp. 92–100. [Crossref]
-  G.M. Rose, A. Hopper, M. De Vivo and A. Tehim: “Phosphodiesterase inhibitors for cognitive enhancement”, Curr. Pharm. Des., Vol. 11, (2005), pp. 3329–3334.
-  D. Djurovic, J. Milic-Askrabic and N. Majkic-Singh: “Serum beta-endorphin level in patients with depression on fluvoxamine”, Farmaco, Vol. 54, (1999), pp. 130–113. [Crossref]
-  A. Zangen, R. Nakash and G. Yadid: “Serotonin-mediated increases in the extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens: a microdialysis study”, J. Neurochem., Vol. 73, (1999), pp. 2569–2574.
-  R. Jadric, I. Zulic, S. Hasic, E. Kiseljakovic, B. Zecevic, J. Radovanovic, E. Icindic-Nakas, M. Winterhalter-Jadric: “Trazodone influence on rat sera beta-endorphins level”, Bosn. J. Basic. Med. Sci., Vol. 4, (2004), pp. 33–36.
-  A. Zangen, R. Nakash, I. Roth-Deri, D.H. Overstreet and G. Yadid: “Impaired release of beta-endorphin in response to serotonin in a rat model of depression”, Neuroscience, Vol. 110, (2002), pp. 389–393. [Crossref]
-  G. Moalem and D.J. Tracey: “Immune and inflammatory mechanisms in neuropathic pain”, Brain Res. Brain Res. Rev., Vol. 51, (2006), pp. 240–264. [Crossref]
-  W. Puehler and C. Stein: “Controlling pain by influencing neurogenic pathways”, Rheum. Dis. Clin. North. Am., Vol. 31, (2005), pp. 103–113. [Crossref]
-  Y.P. Agrawal: “Low dose naltrexone therapy in multiple sclerosis”, Med. Hypotheses, Vol. 64, (2005), pp. 721–724. [Crossref]
-  M. Dokur, C.P. Chen, J.P. Advis and D.K. Sarkar: “Beta-endorphin modulation of interferon-gamma, perforin and granzyme B levels in splenic NK cells: effects of ethanol”, J. Neuroimmunol., Vol. 166, (2005), pp. 29–38. [Crossref]
-  P. Lissoni, F. Malugani and O. Malysheva: “Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system”, Neuro. Endocrinol. Lett., Vol. 23, (2002), pp. 341–344.
-  I.S. Zagon and P.J. McLaughlin: “Opioids and the apoptotic pathway in human cancer cells”, Neuropeptides, Vol. 37, (2003), pp. 79–88. [Crossref]
-  I.S. Zagon and P.J. McLaughlin: “Opioids and differentiation in human cancer cells”, Neuropeptides, Vol. 39, (2005), pp. 495–505. [Crossref]
-  B.M. Berkson, D.M. Rubin and A.J. Berkson: “The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous α-lipoic acid/low-dose naltrexone protocol”, Integr. Cancer. Ther., Vol. 5, (2006), pp. 83–89.
-  K. Makhlouf, M. Comabella and J. Imitola: “Oral salbutamol decreases IL-12 in patients with secondary progressive multiple sclerosis”, J. Neuroimmunol., Vol. 117, (2001), pp. 156–165. [Crossref]
-  K. Makhlouf, H.L. Weiner and S.J. Khoury: “Potential of b2-adrenoceptor agonists as add-on therapy for multiple sclerosis: focus on salbutamol (albuterol)”, CNS Drugs, Vol. 16, (2002), pp. 1–8.
-  G. Ristori, M.G. Buzzi and U. Sabatini: “Use of Bacille Calmette-Guerin (BCG) in multiple sclerosis”, Neurology, Vol. 53, (1999), pp. 1588–1589. [Crossref]
-  R.K. Davis and A.S. Maslow: “Multiple sclerosis in pregnancy: a review”, Obstet. Gynecol. Surv., Vol. 47, (1992), pp. 290–296. [Crossref]
-  S. Sanchez-Ramon, A.J. Navarro and C. Aristimuno: “Pregnancy-induced expansion of regulatory T-lymphocytes may mediate protection to multiple sclerosis activity”, Immunol. Lett., Vol. 96, (2005), pp. 195–201.
-  M. Minagawa, J. Narita, T. Tada, S. Maruyama, T. Shimizu, M. Bannai, H. Oya, K. Hatakeyama and T. Abo: “Mechanisms underlying immunologic states during pregnancy: possible association of the sympathetic nervous system”, Cell. Immunol., Vol. 196, (1999), pp. 1–13. [Crossref]