Endogenous steroid production in the spinal cord and potential involvement in neuropathic pain modulation

Journal of Steroid Biochemistry and Molecular Biology

Volumn 109, Issue 3-5, 2008, Pages 286-293

  Mensah Nyagan, A G ^a   Kibaly, C ^a   Schaeffer, V ^a   Venard, C ^a   Meyer, L ^a   Patte Mensah, C ^a  

^a CNRS   (France)

Author keywords

Neurosteroid; Nociception; Pain; Sensory system; Spinal cord

Indexed keywords

3(OR 17)BETA HYDROXYSTEROID DEHYDROGENASE; 3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; 3ALPHA HYDROXYSTEROID DEHYDROGENASE; CYTOCHROME P450C17; PRASTERONE; PREGNENOLONE; PROGESTERONE; STEROID; STEROID 5ALPHA REDUCTASE;

ENZYME LOCALIZATION; GENE EXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; RADIOIMMUNOASSAY; REAL TIME POLYMERASE CHAIN REACTION; REVIEW; SPINAL CORD; STEROID RELEASE; STEROIDOGENESIS;

ANIMALS; HUMANS; PAIN; PERIPHERAL NERVOUS SYSTEM DISEASES; SIGNAL TRANSDUCTION; SPINAL CORD; STEROIDS;

EID: 44049104356     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2008.03.002     Document Type: Review

References (131)

1. Corpechot C., Robel P., Axelson M., Sjovall J., and Baulieu E.E. Characterization and measurement of dehydroepiandrosterone sulfate in rat brain. Proc. Natl. Acad. Sci. U.S.A. 78 8 (1981) 4704-4707
2. Corpechot C., Synguelakis M., Talha S., Axelson M., Sjovall J., Vihko R., Baulieu E.E., and Robel P. Pregnenolone and its sulfate ester in the rat brain. Brain Res. 270 1 (1983) 119-125
3. Baulieu E.E., Robel P., and Schumacher M. Contemporary Endocrinology (1999), Humana Press, Totowa
4. Mensah-Nyagan A.G., Do-Rego J.L., Beaujean D., Luu-The V., Pelletier G., and Vaudry H. Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system. Pharmacol. Rev. 51 1 (1999) 63-81
5. Compagnone N.A., and Mellon S.H. Neurosteroids: biosynthesis and function of these novel neuromodulators. Front. Neuroendocrinol. 21 1 (2000) 1-56
6. Mayo W., Dellu F., Robel P., Cherkaoui J., Le Moal M., Baulieu E.E., and Simon H. Infusion of neurosteroids into the nucleus basalis magnocellularis affects cognitive processes in the rat. Brain Res. 607 1-2 (1993) 324-328
7. Vallee M., Mayo W., Darnaudery M., Corpechot C., Young J., Koehl M., Le Moal M., Baulieu E.E., Robel P., and Simon H. Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc. Natl. Acad. Sci. U.S.A. 94 26 (1997) 14865-14870
8. Vallee M., Mayo W., Koob G.F., and Le Moal M. Neurosteroids in learning and memory processes. Int. Rev. Neurobiol. 46 (2001) 273-320
9. Purdy R.H., Morrow A.L., Moore Jr. P.H., and Paul S.M. Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain. Proc. Natl. Acad. Sci. U.S.A. 88 10 (1991) 4553-4557
10. Patchev V.K., Hassan A.H., Holsboer D.F., and Almeida O.F. The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus. Neuropsychopharmacology 15 6 (1996) 533-540
11. Zimmerberg B., and Brown R.C. Prenatal experience and postnatal stress modulate the adult neurosteroid and catecholaminergic stress responses. Int. J. Dev. Neurosci. 16 3-4 (1998) 217-228
12. Majewska M.D. Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog. Neurobiol. 38 4 (1992) 379-395
13. Brot M.D., Akwa Y., Purdy R.H., Koob G.F., and Britton K.T. The anxiolytic-like effects of the neurosteroid allopregnanolone: interactions with GABA(A) receptors. Eur. J. Pharmacol. 325 1 (1997) 1-7
14. Hodge C.W., Raber J., McMahon T., Walter H., Sanchez-Perez A.M., Olive M.F., Mehmert K., Morrow A.L., and Messing R.O. Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cepsilon. J. Clin. Invest. 110 7 (2002) 1003-1010
15. Uzunova V., Sheline Y., Davis J.M., Rasmusson A., Uzunov D.P., Costa E., and Guidotti A. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc. Natl. Acad. Sci. U.S.A. 95 6 (1998) 3239-3244
16. Strohle A., Pasini A., Romeo E., Hermann B., Spalletta G., di Michele F., Holsboer F., and Rupprecht R. Fluoxetine decreases concentrations of 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) in major depression. J. Psychiatr. Res. 34 3 (2000) 183-186
17. van Broekhoven F., and Verkes R.J. Neurosteroids in depression: a review. Psychopharmacology (Berl.) 165 2 (2003) 97-110
18. Guth L., Zhang Z., and Roberts E. Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc. Natl. Acad. Sci. U.S.A. 91 25 (1994) 12308-12312
19. Kimonides V.G., Khatibi N.H., Svendsen C.N., Sofroniew M.V., and Herbert J. Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Proc. Natl. Acad. Sci. U.S.A. 95 4 (1998) 1852-1857
20. Frank C., and Sagratella S. Neuroprotective effects of allopregnenolone on hippocampal irreversible neurotoxicity in vitro. Prog. Neuropsychopharmacol. Biol. Psychiatry 24 7 (2000) 1117-1126
21. Haines D.E., Mihailoff G.A., and Yezierski R.P. The spinal cord. In: Haines D.E. (Ed). Fundamental Neuroscience (1997), Churchill Livingstone Inc., New York 129-141
22. Coirini H., Gouezou M., Liere P., Delespierre B., Pianos A., Eychenne B., Schumacher M., and Guennoun R. 3 Beta-hydroxysteroid dehydrogenase expression in rat spinal cord. Neuroscience 113 4 (2002) 883-891
23. Kibaly C., Patte-Mensah C., and Mensah-Nyagan A.G. Molecular and neurochemical evidence for the biosynthesis of dehydroepiandrosterone in the adult rat spinal cord. J. Neurochem. 93 5 (2005) 1220-1230
24. Patte-Mensah C., Kappes V., Freund-Mercier M.J., Tsutsui K., and Mensah-Nyagan A.G. Cellular distribution and bioactivity of the key steroidogenic enzyme, cytochrome P450side chain cleavage, in sensory neural pathways. J. Neurochem. 86 5 (2003) 1233-1246
25. Patte-Mensah C., Li S., and Mensah-Nyagan A.G. Impact of neuropathic pain on the gene expression and activity of cytochrome P450side-chain-cleavage in sensory neural networks. Cell. Mol. Life Sci. 61 17 (2004) 2274-2284
26. Patte-Mensah C., Penning T.M., and Mensah-Nyagan A.G. Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord. J. Comp. Neurol. 477 3 (2004) 286-299
27. Patte-Mensah C., Kibaly C., and Mensah-Nyagan A.G. Substance P inhibits progesterone conversion to neuroactive metabolites in spinal sensory circuit: a potential component of nociception. Proc. Natl. Acad. Sci. U.S.A. 102 25 (2005) 9044-9049
28. Patte-Mensah C., Kibaly C., Boudard D., Schaeffer V., Begle A., Saredi S., Meyer L., and Mensah-Nyagan A.G. Neurogenic pain and steroid synthesis in the spinal cord. J. Mol. Neurosci. 28 1 (2006) 17-31
29. Meyer L., Venard C., Schaeffer V., Patte-Mensah C., and Mensah-Nyagan A.G. The biological activity of 3α-hydroxysteroid oxido-reductase in the spinal cord regulates thermal and mechanical pain thresholds after sciatic nerve injury. Neurobiol. Dis. 30 1 (2008) 30-41
30. Saredi S., Patte-Mensah C., Melcangi R.C., and Mensah-Nyagan A.G. Effect of streptozotocin-induced diabetes on the gene expression and biological activity of 3beta-hydroxysteroid dehydrogenase in the rat spinal cord. Neuroscience 135 3 (2005) 869-877
31. Willis W.D., Westlund K.N., and Carlton S.M. Pain. In: Paxinos G. (Ed). The Rat Nervous System. 2nd edn. (1995), Academic Press Inc., Sydney 725-750
32. Millan M.J. The induction of pain: an integrative review. Prog. Neurobiol. 57 1 (1999) 1-164
33. Millan M.J. Descending control of pain. Prog. Neurobiol. 66 6 (2002) 355-474
34. Suhara K., Gomi T., Sato H., Itagaki E., Takemori S., and Katagiri M. Purification and immunochemical characterization of the two adrenal cortex mitochondrial cytochrome P-450-proteins. Arch. Biochem. Biophys. 190 1 (1978) 290-299
35. Ikushiro S., Kominami S., and Takemori S. Adrenal P-450scc modulates activity of P-45011 beta in liposomal and mitochondrial membranes. Implication of P-450scc in zone specificity of aldosterone biosynthesis in bovine adrenal. J. Biol. Chem. 267 3 (1992) 1464-1469
36. Tsutsui K., and Yamazaki T. Avian neurosteroids. I. Pregnenolone biosynthesis in the quail brain. Brain Res. 678 1-2 (1995) 1-9
37. Usui M., Yamazaki T., Kominami S., and Tsutsui K. Avian neurosteroids. II. Localization of a cytochrome P450scc-like substance in the quail brain. Brain Res. 678 1-2 (1995) 10-20
38. Ukena K., Usui M., Kohchi C., and Tsutsui K. Cytochrome P450 side-chain cleavage enzyme in the cerebellar Purkinje neuron and its neonatal change in rats. Endocrinology 139 1 (1998) 137-147
39. Roby K.F., Larsen D., Deb S., and Soares M.J. Generation and characterization of antipeptide antibodies to rat cytochrome P-450 side-chain cleavage enzyme. Mol. Cell. Endocrinol. 79 1-3 (1991) 13-20
40. Kennedy P.G. Neural cell markers and their applications to neurology. J. Neuroimmunol. 2 1 (1982) 35-53
41. Nagle R.B. Intermediate filaments: a review of the basic biology. Am. J. Surg. Pathol. 12 Suppl. 1 (1988) 4-16
42. Fuxe K., and Agnati L.F. Volume Transmission in the Brain: Novel Mechanisms for Neuronal Transmission (1992), Raven Press, New York
43. Mensah-Nyagan A.G., Feuilloley M., Dupont E., Do-Rego J.L., Leboulenger F., Pelletier G., and Vaudry H. Immunocytochemical localization and biological activity of 3 beta-hydroxysteroid dehydrogenase in the central nervous system of the frog. J. Neurosci. 14 12 (1994) 7306-7318
44. Mensah-Nyagan A.G., Do-Rego J.L., Feuilloley M., Marcual A., Lange C., Pelletier G., and Vaudry H. In vivo and in vitro evidence for the biosynthesis of testosterone in the telencephalon of the female frog. J. Neurochem. 67 1 (1996) 413-422
45. Mensah-Nyagan A.G., Feuilloley M., Do-Rego J.L., Marcual A., Lange C., Tonon M.C., Pelletier G., and Vaudry H. Localization of 17beta-hydroxysteroid dehydrogenase and characterization of testosterone in the brain of the male frog. Proc. Natl. Acad. Sci. U.S.A. 93 4 (1996) 1423-1428
46. Mensah-Nyagan A.G., Beaujean D., Luu-The V., Pelletier G., and Vaudry H. Anatomical and biochemical evidence for the synthesis of unconjugated and sulfated neurosteroids in amphibians. Brain Res. Brain Res. Rev. 37 1-3 (2001) 13-24
47. Mensah-Nyagan A.G., Do-Rego J.L., Beaujean D., Luu-The V., Pelletier G., and Vaudry H. Regulation of neurosteroid biosynthesis in the frog diencephalon by GABA and endozepines. Horm. Behav. 40 2 (2001) 218-225
48. Hales D.B., Sha L.L., and Payne A.H. Testosterone inhibits cAMP-induced de novo synthesis of Leydig cell cytochrome P-450(17 alpha) by an androgen receptor-mediated mechanism. J. Biol. Chem. 262 23 (1987) 11200-11206
49. Hales D.B. Interleukin-1 inhibits Leydig cell steroidogenesis primarily by decreasing 17 alpha-hydroxylase/C17-20 lyase cytochrome P450 expression. Endocrinology 131 5 (1992) 2165-2172
50. Kuhn-Velten W.N., and Lessmann M. Ketoconazole inhibition of the bifunctional cytochrome P450c17 does not affect androgen formation from the endogenous lyase substrate. The catalytic site remains refractory in the course of intermediary hydroxyprogesterone processing. Biochem. Pharmacol. 44 12 (1992) 2371-2378
51. Swart P., Swart A.C., Waterman M.R., Estabrook R.W., and Mason J.I. Progesterone 16 alpha-hydroxylase activity is catalyzed by human cytochrome P450 17 alpha-hydroxylase. J. Clin. Endocrinol. Metab. 77 1 (1993) 98-102
52. Sanne J.L., and Krueger K.E. Expression of cytochrome P450 side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase in the rat central nervous system: a study by polymerase chain reaction and in situ hybridization. J. Neurochem. 65 2 (1995) 528-536
53. Saitoh H., Hirato K., Yanaihara T., and Nakayama T. A study of 5 alpha-reductase in human fetal brain. Endocrinol. Jpn. 29 4 (1982) 461-467
54. Melcangi R.C., Celotti F., Castano P., and Martini L. Differential localization of the 5 alpha-reductase and the 3 alpha-hydroxysteroid dehydrogenase in neuronal and glial cultures. Endocrinology 132 3 (1993) 1252-1259
55. Pelletier G., Luu-The V., and Labrie F. Immunocytochemical localization of 5 alpha-reductase in rat brain. Mol. Cell. Neurosci. 5 5 (1994) 394-399
56. Martini L., Celotti F., and Melcangi R.C. Testosterone and progesterone metabolism in the central nervous system: cellular localization and mechanism of control of the enzymes involved. Cell. Mol. Neurobiol. 16 3 (1996) 271-282
57. Negri-Cesi P., Poletti A., and Celotti F. Metabolism of steroids in the brain: a new insight into the role of 5alpha-reductase and aromatase in brain differentiation and functions. J. Steroid Biochem. Mol. Biol. 58 5-6 (1996) 455-466
58. Stoffel-Wagner B., Watzka M., Steckelbroeck S., Ludwig M., Clusmann H., Bidlingmaier F., Casarosa E., Luisi S., Elger C.E., and Beyenburg S. Allopregnanolone serum levels and expression of 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase isoforms in hippocampal and temporal cortex of patients with epilepsy. Epilepsy Res. 54 1 (2003) 11-19
59. Celotti F., Melcangi R.C., and Martini L. The 5 alpha-reductase in the brain: molecular aspects and relation to brain function. Front. Neuroendocrinol. 13 2 (1992) 163-215
60. Poletti A., Coscarella A., Negri-Cesi P., Colciago A., Celotti F., and Martini L. 5 alpha-reductase isozymes in the central nervous system. Steroids 63 5-6 (1998) 246-251
61. Poletti A., Negri-Cesi P., Rabuffetti M., Colciago A., Celotti F., and Martini L. Transient expression of the 5alpha-reductase type 2 isozyme in the rat brain in late fetal and early postnatal life. Endocrinology 139 4 (1998) 2171-2178
62. Torres J.M., and Ortega E. Differential regulation of steroid 5alpha-reductase isozymes expression by androgens in the adult rat brain. FASEB J. 17 11 (2003) 1428-1433
63. Pozzi P., Bendotti C., Simeoni S., Piccioni F., Guerini V., Marron T.U., Martini L., and Poletti A. Androgen 5-alpha-reductase type 2 is highly expressed and active in rat spinal cord motor neurones. J. Neuroendocrinol. 15 9 (2003) 882-887
64. Julius D., and Basbaum A.I. Molecular mechanisms of nociception. Nature 413 6852 (2001) 203-210
65. Andersson S., and Russell D.W. Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases. Proc. Natl. Acad. Sci. U.S.A. 87 10 (1990) 3640-3644
66. Thigpen A.E., Cala K.M., and Russell D.W. Characterization of Chinese hamster ovary cell lines expressing human steroid 5 alpha-reductase isozymes. J. Biol. Chem. 268 23 (1993) 17404-17412
67. Raff M.C., Mirsky R., Fields K.L., Lisak R.P., Dorfman S.H., Silberberg D.H., Gregson N.A., Leibowitz S., and Kennedy M.C. Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture. Nature 274 5673 (1978) 813-816
68. Matus A. Microtubule-associated proteins. Curr. Opin. Cell. Biol. 2 1 (1990) 10-14
69. Melcangi R.C., Celotti F., Ballabio M., Castano P., Poletti A., Milani S., and Martini L. Ontogenetic development of the 5 alpha-reductase in the rat brain: cerebral cortex, hypothalamus, purified myelin and isolated oligodendrocytes. Brain Res. Dev. Brain Res. 44 2 (1988) 181-188
70. Melcangi R.C., Celotti F., Ballabio M., Poletti A., Castano P., and Martini L. Testosterone 5 alpha-reductase activity in the rat brain is highly concentrated in white matter structures and in purified myelin sheaths of axons. J. Steroid Biochem. 31 2 (1988) 173-179
71. Poletti A., Celotti F., Rumio C., Rabuffetti M., and Martini L. Identification of type 1 5alpha-reductase in myelin membranes of male and female rat brain. Mol. Cell. Endocrinol. 129 2 (1997) 181-190
72. Pawlowski J.E., Huizinga M., and Penning T.M. Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. J. Biol. Chem. 266 14 (1991) 8820-8825
73. Jez J.M., Bennett M.J., Schlegel B.P., Lewis M., and Penning T.M. Comparative anatomy of the aldo-keto reductase superfamily. Biochem. J. 326 Pt 3 (1997) 625-636
74. Jez J.M., Flynn T.G., and Penning T.M. A new nomenclature for the aldo-keto reductase superfamily. Biochem. Pharmacol. 54 6 (1997) 639-647
75. Penning T.M., Jin Y., Heredia V.V., and Lewis M. Structure-function relationships in 3alpha-hydroxysteroid dehydrogenases: a comparison of the rat and human isoforms. J. Steroid Biochem. Mol. Biol. 85 2-5 (2003) 247-255
76. Krieger N.R., and Scott R.G. 3 alpha-Hydroxysteroid oxidoreductase in rat brain. J. Neurochem. 42 3 (1984) 887-890
77. Krieger N.R., and Scott R.G. Nonneuronal localization for steroid converting enzyme: 3 alpha-hydroxysteroid oxidoreductase in olfactory tubercle of rat brain. J. Neurochem. 52 6 (1989) 1866-1870
78. Khanna M., Qin K.N., and Cheng K.C. Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans. J. Steroid Biochem. Mol. Biol. 53 1-6 (1995) 41-46
79. Smithgall T.E., and Penning T.M. Electrophoretic and immunochemical characterization of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenases of rat tissues. Biochem. J. 254 3 (1988) 715-721
80. Jez J.M., Schlegel B.P., and Penning T.M. Characterization of the substrate binding site in rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase. The roles of tryptophans in ligand binding and protein fluorescence. J. Biol. Chem. 271 47 (1996) 30190-30198
81. Paul S.M., and Purdy R.H. Neuroactive steroids. FASEB J. 6 6 (1992) 2311-2322
82. Frye C.A., Duncan J.E., Basham M., and Erskine M.S. Behavioral effects of 3 alpha-androstanediol. II. Hypothalamic and preoptic area actions via a GABAergic mechanism. Behav. Brain Res. 79 1-2 (1996) 119-130
83. Frye C.A., Rhodes M.E., Rosellini R., and Svare B. The nucleus accumbens as a site of action for rewarding properties of testosterone and its 5alpha-reduced metabolites. Pharmacol. Biochem. Behav. 74 1 (2002) 119-127
84. Reddy D.S. Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions?. Trends Pharmacol. Sci. 24 3 (2003) 103-106
85. Melcangi R.C., Poletti A., Cavarretta I., Celotti F., Colciago A., Magnaghi V., Motta M., Negri-Cesi P., and Martini L. The 5alpha-reductase in the central nervous system: expression and modes of control. J. Steroid Biochem. Mol. Biol. 65 1-6 (1998) 295-299
86. Lumbroso S., Sandillon F., Georget V., Lobaccaro J.M., Brinkmann A.O., Privat A., and Sultan C. Immunohistochemical localization and immunoblotting of androgen receptor in spinal neurons of male and female rats. Eur. J. Endocrinol. 134 5 (1996) 626-632
87. Matsumoto A. Hormonally induced neuronal plasticity in the adult motoneurons. Brain Res. Bull. 44 4 (1997) 539-547
88. Kastrup Y., Hallbeck M., Amandusson A., Hirata S., Hermanson O., and Blomqvist A. Progesterone receptor expression in the brainstem of the female rat. Neurosci. Lett. 275 2 (1999) 85-88
89. Labombarda F., Guennoun R., Gonzalez S., Roig P., Lima A., Schumacher M., and De Nicola A.F. Immunocytochemical evidence for a progesterone receptor in neurons and glial cells of the rat spinal cord. Neurosci. Lett. 288 1 (2000) 29-32
90. Frye C.A. The role of neurosteroids and non-genomic effects of progestins and androgens in mediating sexual receptivity of rodents. Brain Res. Brain Res. Rev. 37 1-3 (2001) 201-222
91. Lambert J.J., Belelli D., Peden D.R., Vardy A.W., and Peters J.A. Neurosteroid modulation of GABAA receptors. Prog. Neurobiol. 71 1 (2003) 67-80
92. Bennett G.J., and Xie Y.K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33 1 (1988) 87-107
93. Gispen W.H., and Biessels G.J. Cognition, and synaptic plasticity in diabetes mellitus. Trends Neurosci. 23 11 (2000) 542-549
94. Varsik P., Kucera P., Buranova D., and Balaz M. Is the spinal cord lesion rare in diabetes mellitus? Somatosensory evoked potentials and central conduction time in diabetes mellitus. Med. Sci. Monit. 7 4 (2001) 712-715
95. Jacobson A.M., Samson J.A., Weinger K., and Ryan C.M. Diabetes, the brain, and behavior: is there a biological mechanism underlying the association between diabetes and depression?. Int. Rev. Neurobiol. 51 (2002) 455-479
96. Courteix C., Eschalier A., and Lavarenne J. Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain. Pain 53 1 (1993) 81-88
97. Bitar M.S., and Pilcher C.W. Diabetes attenuates the response of the lumbospinal noradrenergic system to idazoxan. Pharmacol. Biochem. Behav. 67 2 (2000) 247-255
98. Zurek J.R., Nadeson R., and Goodchild C.S. Spinal and supraspinal components of opioid antinociception in streptozotocin-induced diabetic neuropathy in rats. Pain 90 1-2 (2001) 57-63
99. Chen S.R., and Pan H.L. Hypersensitivity of spinothalamic tract neurons associated with diabetic neuropathic pain in rats. J. Neurophysiol. 87 6 (2002) 2726-2733
100. Chen S.R., and Pan H.L. Antinociceptive effect of morphine, but not mu opioid receptor number, is attenuated in the spinal cord of diabetic rats. Anesthesiology 99 6 (2003) 1409-1414
101. Kapur D. Neuropathic pain and diabetes. Diabetes Metab. Res. Rev. 19 Suppl. 1 (2003) S9-S15
102. De Koninck Y., and Henry J.L. Substance P-mediated slow excitatory postsynaptic potential elicited in dorsal horn neurons in vivo by noxious stimulation. Proc. Natl. Acad. Sci. U.S.A. 88 24 (1991) 11344-11348
103. Mantyh P.W., Rogers S.D., Honore P., Allen B.J., Ghilardi J.R., Li J., Daughters R.S., Lappi D.A., Wiley R.G., and Simone D.A. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278 5336 (1997) 275-279
104. Nichols M.L., Allen B.J., Rogers S.D., Ghilardi J.R., Honore P., Luger N.M., Finke M.P., Li J., Lappi D.A., Simone D.A., and Mantyh P.W. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286 5444 (1999) 1558-1561
105. Ueda H., Inoue M., Yoshida A., Mizuno K., Yamamoto H., Maruo J., Matsuno K., and Mita S. Metabotropic neurosteroid/sigma-receptor involved in stimulation of nociceptor endings of mice. J. Pharmacol. Exp. Ther. 298 2 (2001) 703-710
106. Uchida H., Mizuno K., Yoshida A., and Ueda H. Neurosteroid-induced hyperalgesia through a histamine release is inhibited by progesterone and p,p′-DDE, an endocrine disrupting chemical. Neurochem. Int. 42 5 (2003) 401-407
107. De Roo M., Rodeau J.L., and Schlichter R. Dehydroepiandrosterone potentiates native ionotropic ATP receptors containing the P2X2 subunit in rat sensory neurones. J. Physiol. 552 Pt 1 (2003) 59-71
108. Chen S.C., Chang T.J., and Wu F.S. Competitive inhibition of the capsaicin receptor-mediated current by dehydroepiandrosterone in rat dorsal root ganglion neurons. J. Pharmacol. Exp. Ther. 311 2 (2004) 529-536
109. Dawson-Basoa M., and Gintzler A.R. Involvement of spinal cord delta opiate receptors in the antinociception of gestation and its hormonal simulation. Brain Res. 757 1 (1997) 37-42
110. Dawson-Basoa M., and Gintzler A.R. Gestational and ovarian sex steroid antinociception: synergy between spinal kappa and delta opioid systems. Brain Res. 794 1 (1998) 61-67
111. Thomas A.J., Nockels R.P., Pan H.Q., Shaffrey C.I., and Chopp M. Progesterone is neuroprotective after acute experimental spinal cord trauma in rats. Spine 24 20 (1999) 2134-2138
112. Koltzenburg M. Painful neuropathies. Curr. Opin. Neurol. 11 5 (1998) 515-521
113. Woolf C.J., and Mannion R.J. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 353 9168 (1999) 1959-1964
114. Goodchild C.S., Guo Z., and Nadeson R. Antinociceptive properties of neurosteroids. I. Spinally-mediated antinociceptive effects of water-soluble aminosteroids. Pain 88 1 (2000) 23-29
115. Goodchild C.S., Robinson A., and Nadeson R. Antinociceptive properties of neurosteroids IV: pilot study demonstrating the analgesic effects of alphadolone administered orally to humans. Br. J. Anaesth. 86 4 (2001) 528-534
116. Gambhir M., Mediratta P.K., and Sharma K.K. Evaluation of the analgesic effect of neurosteroids and their possible mechanism of action. Indian J. Physiol. Pharmacol. 46 2 (2002) 202-208
117. Belelli D., and Lambert J.J. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat. Rev. Neurosci. 6 7 (2005) 565-575
118. Waldvogel H.J., Faull R.L., Jansen K.L., Dragunow M., Richards J.G., Mohler H., and Streit P. GABA, GABA receptors and benzodiazepine receptors in the human spinal cord: an autoradiographic and immunohistochemical study at the light and electron microscopic levels. Neuroscience 39 2 (1990) 361-385
119. Bohlhalter S., Mohler H., and Fritschy J.M. Inhibitory neurotransmission in rat spinal cord: co-localization of glycine- and GABAA-receptors at GABAergic synaptic contacts demonstrated by triple immunofluorescence staining. Brain Res. 642 1-2 (1994) 59-69
120. Bohlhalter S., Weinmann O., Mohler H., and Fritschy J.M. Laminar compartmentalization of GABAA-receptor subtypes in the spinal cord: an immunohistochemical study. J. Neurosci. 16 1 (1996) 283-297
121. Gutierrez A., Khan Z.U., and De Blas A.L. Immunocytochemical localization of the alpha 6 subunit of the gamma-aminobutyric acidA receptor in the rat nervous system. J. Comp. Neurol. 365 3 (1996) 504-510
122. Nadeson R., and Goodchild C.S. Antinociceptive properties of neurosteroids. II. Experiments with Saffan and its components alphaxalone and alphadolone to reveal separation of anaesthetic and antinociceptive effects and the involvement of spinal cord GABA(A) receptors. Pain 88 1 (2000) 31-39
123. Todorovic S.M., and Lingle C.J. Pharmacological properties of T-type Ca2+ current in adult rat sensory neurons: effects of anticonvulsant and anesthetic agents. J. Neurophysiol. 79 1 (1998) 240-252
124. Todorovic S.M., Prakriya M., Nakashima Y.M., Nilsson K.R., Han M., Zorumski C.F., Covey D.F., and Lingle C.J. Enantioselective blockade of T-type Ca2+ current in adult rat sensory neurons by a steroid that lacks gamma-aminobutyric acid-modulatory activity. Mol. Pharmacol. 54 5 (1998) 918-927
125. Pathirathna S., Brimelow B.C., Jagodic M.M., Krishnan K., Jiang X., Zorumski C.F., Mennerick S., Covey D.F., Todorovic S.M., and Jevtovic-Todorovic V. New evidence that both T-type calcium channels and GABAA channels are responsible for the potent peripheral analgesic effects of 5alpha-reduced neuroactive steroids. Pain 114 3 (2005) 429-443
126. Murakami K., Fellous A., Baulieu E.E., and Robel P. Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly. Proc. Natl. Acad. Sci. U.S.A. 97 7 (2000) 3579-3584
127. Plassart-Schiess E., and Baulieu E.E. Neurosteroids: recent findings. Brain Res. Brain Res. Rev. 37 1-3 (2001) 133-140
128. Woolf C.J., and Salter M.W. Neuronal plasticity: increasing the gain in pain. Science 288 5472 (2000) 1765-1769
129. Whiteside G.T., and Munglani R. Cell death in the superficial dorsal horn in a model of neuropathic pain. J. Neurosci. Res. 64 2 (2001) 168-173
130. Maione S., Siniscalco D., Galderisi U., de Novellis V., Uliano R., Di Bernardo G., Berrino L., Cascino A., and Rossi F. Apoptotic genes expression in the lumbar dorsal horn in a model neuropathic pain in rat. Neuroreport 13 1 (2002) 101-106
131. Joseph E.K., and Levine J.D. Caspase signalling in neuropathic and inflammatory pain in the rat. Eur. J. Neurosci. 20 11 (2004) 2896-2902