PAIN
Volume 143, Issue 1 , Pages 12-20 , May 2009

Neuroactive steroids inhibit spinal reflex potentiation by selectively enhancing specific spinal GABAA receptor subtypes

  • Hsien-Yu Peng

      Affiliations

    • Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd, Section 1, Taichung 40201, Taiwan
    • Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan
  • ,
  • Gin-Den Chen

      Affiliations

    • Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung, Taiwan
    • These two authors contributed equally to this study.
  • ,
  • Shin-Da Lee

      Affiliations

    • School of Physical Therapy, Graduate Institute of Rehabilitation Science, College of Medicine, China Medical University, Taichung, Taiwan
  • ,
  • Cheng-Yuan Lai

      Affiliations

    • Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd, Section 1, Taichung 40201, Taiwan
    • Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan
  • ,
  • Chun-Hsien Chiu

      Affiliations

    • Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd, Section 1, Taichung 40201, Taiwan
    • Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan
  • ,
  • Chen-Li Cheng

      Affiliations

    • Urology Division, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
  • ,
  • Yu-Shuo Chang

      Affiliations

    • Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd, Section 1, Taichung 40201, Taiwan
  • ,
  • Ming-Chun Hsieh

      Affiliations

    • Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd, Section 1, Taichung 40201, Taiwan
  • ,
  • Kwong-Chung Tung

      Affiliations

    • Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan
  • ,
  • Tzer-Bin Lin

      Affiliations

    • Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd, Section 1, Taichung 40201, Taiwan
    • Medical Department, Saint Paul’s Hospital, Taoyuan, Taiwan
    • Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
    • These two authors contributed equally to this study.
    • Corresponding Author InformationCorresponding author. Address: Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd, Section 1, Taichung 40201, Taiwan. Tel.: +886 4 2473 0022; fax: +886 4 2473 9030.

Received 23 July 2008 ,Revised 15 December 2008 ,Accepted 16 December 2008.

References 

  1. Agis-Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, et al. Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis. Proc Natl Acad Sci USA. 2006;103:14602–14607
  2. Baulieu EE, Robel P. Neurosteroids: a new brain function?. J Steroid Biochem Mol Biol. 1990;37:395–403
  3. Belelli D, Casula A, Ling A, Lambert JJ. The influence of subunit composition on the interaction of neurosteroids with GABAA receptors. Neuropharmacology. 2002;43:651–661
  4. Bogdanov Y, Michels G, Armstrong-Gold C, Haydon PG, Lindstrom J, Pangalos M, et al. Synaptic GABAA receptors are directly recruited from their extrasynaptic counterparts. EMBO J. 2006;25:4381–4389
  5. Brussaard AB, Wossink J, Lodder JC, Kits KS. Progesterone metabolite prevents protein kinase C-dependent modulation of gammaaminobutyric acid type A receptors in oxytocin neurons. Proc Natl Acad Sci USA. 2000;97:3625–3630
  6. Celik O, Hascalik S, Tagluk ME, Elter K, Parlakpinar H, Acet A. Assessment of myoelectrical signal parameters in estrogen, progesterone, and human chorionic gonadotropin administered in nonpregnant rat myometrium after ovariectomy. Fertil Steril. 2008;89:188–198
  7. Chang Y, Wang R, Barot S, Weiss DS. Stoichiometry of a recombinant GABA-A receptor. J Neurosci. 1990;16:534–541
  8. Chen GD, Peng HY, Tung KC, Cheng CL, Chen YJ, Liao JM, et al. Descending facilitation of spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats. Am J Physiol Renal Physiol. 2007;293:F1115–F1122
  9. Chen GD, Peng ML, Wang PY, Lee SD, Chang HM, Pan SF, et al. Calcium/calmodulin-dependent kinase II mediates NO-elicited PKG activation to participate in spinal reflex potentiation in anesthetized rats. Am J Physiol Regul Integr Comp Physiol. 2008;294:R487–R493
  10. Chen KJ, Chen LW, Liao JM, Chen CH, Ho YC, Ho YC, et al. Effects of a calcineurin inhibitor, tacrolimus (FK-506), on glutamate dependent potentiation in pelvic–urethral reflex in anesthetized rats. Neuroscience. 2006;138:69–76
  11. Chen KJ, Peng HY, Cheng CL, Chen CH, Liao JM, Ho YC, et al. Acute unilateral ureter distension inhibits glutamate-dependent spinal pelvic–urethra reflex potentiation via GABAergic neurotransmission in anesthetized rats. Am J Physiol Renal Physiol. 2007;292:F1007–F1015
  12. Chen SL, Huang YH, Kao YL, Chen GD, Cheng CL, Peng HY, et al. Acute anal stretch inhibits NMDA-dependent pelvic–urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats. Am J Physiol Renal Physiol. 2008;295:F923–F931
  13. Concas A, Mostallino MC, Porcu P, Follesa P, Barbaccia ML, Trabucchi M, et al. Role of brain allopregnanolone in the plasticity of gamma-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery. Proc Natl Acad Sci USA. 1998;95:13284–13289
  14. Cruz Y, Downie JW. Abdominal muscle activity during voiding in female rats with normal or irritated bladder. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1436–R1445
  15. Dang K, Bowery NG, Urban L. Interaction of gamma-aminobutyric acid receptor type B receptors and calcium channels in nociceptive transmission studied in the mouse hemisected spinal cord in vitro: withdrawal symptoms related to baclofen treatment. Neurosci Lett. 2004;361:72–75
  16. Essrich C, Lorez M, Benson JA, Fritschy JM, Luscher B. Postsynaptic clustering of major GABA(A) receptor subtypes requires the gamma 2 subunit and gephyrin. Nat Neurosci. 1998;1:563–571
  17. Edinger KL, Frye CA. Testosterone’s analgesic, anxiolytic, and cognitive-enhancing effects may be due in part to actions of its 5alpha-reduced metabolites in hippocampus. Behav Neurosci. 2004;118:1352–1364
  18. Edinger KL, Frye CA. Testosterone’s anti-anxiety and analgesic effects may be due in part to actions of its 5α-reduced metabolites in the hippocampus. Psychoneuroendocrinology. 2005;30:418–430
  19. Fancsik A, Linn DM, Tasker JG. Neurosteroid modulation of GABA IPSCs is phosphorylation dependent. J Neurosci. 2000;20:3067–3075
  20. Frye CA, Walf AA. Estrogen and/or progesterone administered systemically or to the amygdale can have anxiety-, fear-, and pain reducing effects in ovariectomized rats. Behav Neurosci. 2004;118:306–313
  21. Frye CA, Walf AA, Rhodes ME, Harney JP. Progesterone enhances motor, anxiolytic, analgesic, and antidressive behavior of wide-type mice, but not those deficient in type 1,5-alpha-reductase. Brain Res. 2004;104:116–124
  22. Grassi S, Frondaroli A, Dieni C, Dutia MB, Pettorossi VE. Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibule nuclei. Eur J Neurosci. 2007;26:23–32
  23. Greenspan JD, Craft RM, Resche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB, et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007;132:26–45
  24. Griffiths J, Lovick T. Withdrawal from progesterone increases expression of alpha4, beta1 and delta GABA (A) receptor subunits in neurons in the periaqueductal gray matter in female Wistar rats. J Comp Neurol. 2005;486:89–97
  25. Gulinello M, Orman R, Smith SS. Sex differences in anxiety, sensorimotor gating and expression of the alpha4 subunit of the GABAA receptor in the amygdala after progesterone withdrawal. Eur J Neurosci. 2003;17:641–648
  26. Harney SC, Frenguelli BG, Lambert JJ. Phosphorylation influences neurosteroid modulation of synaptic GABA(A) receptors in rat CA1 and dentate gyrus neurones. Neuropharmacology. 2003;45:873–883
  27. Hevers W, Luddens H. The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes. Mol Neurobiol. 1998;18:35–86
  28. Hodge CW, Raber J, McMahon T, Walter H, Sanchez-Perez AM, Olive MF, et al. Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase C epsilon. J Clin Invest. 2002;110:1003–1010
  29. Kawaguchi SY, Hirano T. Sustained structural changes of GABAA receptor-associated protein underlies long-term potentiation at inhibitory synapses on a cerebellar Purkinje neuron. J Neurosci. 2007;27:6788–6799
  30. Kibaly C, Meyer L, Patte-Mensah C, Mensah-Nyagan AG. Biochemical and functional evidence for the control of pain mechanism by dehydroepaianddroosterone endogenously synthesized in the spinal cord. FASEB J. 2007;22:93–104
  31. Kittler JT, Moss SJ. Modulation of GABA(A) receptor activity by phosphorylation and receptor trafficking: implications for the efficacy of synaptic inhibition. Curr Opin Neurobiol. 2003;13:341–347
  32. Knabl J, Witschi R, Hösl K, Reinold H, Zeilhofer UB, Ahmadi S, et al. Reversal of pathological pain through specific spinal GABAA receptor subtypes. Nature. 2008;451:330–334
  33. Li XT, O’Malley BW. Unfolding the action of progesterone receptors. J Biol Chem. 2003;278:39261–39264
  34. Liao JM, Huang PC, Pan SF, Chen MJ, Tung KC, Peng HY, et al. Spinal glutamatergic NMDA-dependent pelvic nerve-to-external urethra sphincter reflex potentiation caused by a mechanical stimulation in anesthetized rats. Am J Physiol Renal Physiol. 2007;292:F1791–F1801
  35. Liao JM, Yang CH, Cheng CL, Pan SF, Chen MJ, Huang PC, et al. Spinal glutamatergic NMDA-dependent cyclic pelvic nerve-to-external urethra sphincte. Am J Physiol Renal Physiol. 2007;293:F790–F800
  36. Lin SY, Chen GD, Liao JM, Pan SF, Chen MJ, Chen CJ, et al. Estrogen modulates the spinal NMDA-mediated pelvic nerve-to-urethra reflex plasticity in rats. Endocrinology. 2006;147:2956–2963
  37. Lin TB. Dynamic pelvic–pudendal reflex plasticity mediated by glutamate in anesthetized rats. Neuropharmacology. 2003;44:163–170
  38. Lovic TA, Griffiths JL, Dunn SMJ, Martin IL. Changes in GABAA receptor subunit expression in the midbrain during the oestrous cycle in Wistar rats. Neuroscience. 2006;131:397–405
  39. Maguire J, Mody I. Neurosteroid synthesis-mediated regulation of GABAA receptor: relevance to the ovarian cycle and stress. J Neurosci. 2007;27:2155–2162
  40. Maguire JL, Stell BM, Rafizadeh M, Mody I. Ovarian cycle-linked changes in GABAA receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat Neurosci. 2005;8:797–804
  41. Mensah-Nyagan AG, kibaly C, Schaeffer V, Venard C, Meyer L, Patte-Mensah C. Endogenous steroid production in the spinal cord and potential involvement in neuropathic pain modulation. J Steroid Biochem Mol Biol. 2008;109:286–293
  42. Meyer L, Venard C, Schaeffer V, Patte-Mensah C, Mensah-Nyagan AG. The biological activity of 3 alpha-hydroxysteroid oxido-reductase in the spinal cord regulates thermal and mechanical pain thresholds after saciatic nerve injury. Neurobiol Dis. 2008;30:30–41
  43. Pan SF, Peng HY, Chen CC, Chen MJ, Lee SD, Cheng CL, et al. Nicotine-activated descending facilitation on spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats. Am J Physiol Renal Physiol. 2008;294:F1195–F1204
  44. Peng HY, Chang HM, Chang SY, Tung KC, Lee SD, Chou D, et al. Orexin-A modulates glutamatergic NMDA-dependent spinal reflex potentiation via inhibition of NR2B subunit. Am J Physiol Endocrinol Metab. 2008;295:E117–E129
  45. Peng HY, Chang HM, Chang SY, Tung KC, Lee SD, Chou D, et al. TRPV1 mediates the uterine capsaicin-induced NMDA NR2B-dependent cross-organ reflex sensitization in anesthetized rats. Am J Physiol Renal Physiol. 2008;295:F1324–F1335
  46. Peng H-Y, Chen G-D, Tung K-C, Lai C-Y, Hsien M-C, Chiu C-H, et al. Colon mustard oil instillation induced cross-organ reflex sensitization on the pelvic-urethra reflex activity in rats. Pain. 2009;142:75–88
  47. Peng HY, Chien YW, Lee SD, Ho YC, Chou D, Chen GD, et al. Glutamate-mediated spinal reflex potentiation involves ERK 1/2 phosphorylation in anesthetized rats. Neuropharmacology. 2008;54:686–698
  48. Peng HY, Huang PC, Liao JM, Tung KC, Lee SD, Cheng CL, et al. Estrous cycle variation of TRPV1-mediated cross-organ sensitization between uterus and NMDA-dependent pelvic–urethra reflex activity. Am J Physiol Endocrinol Metab. 2008;295:E559–E568
  49. Poisbeau P, Patte-Mensah C, Keller AF, Barrot M, Breton JD, Luis-Delgado OE, et al. Inflammatory pain upregulates spinal inhibition via endogenous neurosteroid production. J Neurosci. 2005;25:11768–11776
  50. Riekki R, Pavlov I, Tornberg J, Lauri SE, Airaksinen MS, Taira T. Altered synaptic dynamics and hippocampal excitability but normal long-term plasticity in mice lacking hyperpolarizing GABAA receptor-mediated inhibition in CA1 pyramidal neurons. J Neurophysiol. 2008;99:3075–3089
  51. Sarihi A, Jiang B, Komai A, Sohya K, Yanagawa Y, Tsumoto T. Metabotropic glutamate receptor type 5-dependent long-term potentiation of excitatory synapses on fast-spiking GABAergic neurons in mouse visual cortex. J Neurosci. 2008;28:1223–1235
  52. Shen H, Gong QH, Yuan M, Smith SS. Short-term steroid treatment increases delta GABA(A) receptor subunit expression in rat CA1 hippocampus: pharmacological and behavioral effects. Neuropharmacology. 2005;49:573–586
  53. Smith SS, Shen H, Gong SQ, Zhou X. Neurosteroid regulation of GABAA receptors: focus on the alpha 4 and delta subunits. Pharmacol Ther. 2007;116:58–76
  54. Steward O, Schuman EM. Protein synthesis at synaptic sites on dendrites. Annu Rev Neurosci. 2001;24:299–325
  55. Sur C, Farrar S, Kerby J, Whiting PJ, Atack JR, McKernan RM. Preferential coassembly of alpha-4 and delta subunits of the GABAA receptor in rat thalamus. Mol Pharmacol. 1999;56:110–115
  56. Walf AA, Frye CA. Anti-nociception following exposure to trimethylthiazoline, peripheral or intra-amygdala estrogen and/or progesterone. Behav Brain Res. 2003;15:77–85
  57. Wang DD, Kriegstein A. GABA regulates excitatory synapse formation in the neocortex via NMDA receptor activation. J Neurosci. 2008;28:5547–5558
  58. Wei WZ, Zhang NH, Peng ZC, Houser CR, Mody I. Perisynaptic localization of delta subunit-containing GABA(A) receptors and their activation by GABA spillover in the mouse dentate gyrus. J Neurosci. 2003;23:10650–10661
  59. Wohlfarth KM, Bianchi MT, Macdonald RL. Enhanced neurosteroid potentiation of ternary GABAA receptors containing the delta subunit. J Neurosci. 2002;22:1541–1549

PII: S0304-3959(08)00763-X

doi: 10.1016/j.pain.2008.12.023

PAIN
Volume 143, Issue 1 , Pages 12-20 , May 2009