Analgesic strategies aimed at stimulating the endogenous production of allopregnanolone

Frontiers in Cellular Neuroscience

Volumn 8, Issue JUN, 2014, Pages

  Poisbeau, Pierrick ^a   Keller, Anne Florence ^a,b   Aouad, Maya ^a   Kamoun, Nisrine ^a   Groyer, Ghislaine ^c   Schumacher, Michael ^c  

^a CNRS   (France)

^b Rhenovia Pharma   (France)

^c INSERM   (France)

Author keywords

Allodynia; Etifoxine; Hyperalgesia; Neurosteroids; Nociception; Pain

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; 4 AMINOBUTYRIC ACID A RECEPTOR; ANALGESIC AGENT; ETIFOXINE; NEUROSTEROID; OXALIPLATIN; OXYTOCIN; PACLITAXEL; STEROID 5ALPHA REDUCTASE; STEROID ANALGESIC AGENT; UNCLASSIFIED DRUG; VINCRISTINE SULFATE;

ALLODYNIA; HORMONAL REGULATION; HYPERSENSITIVITY; NONHUMAN; PAIN; PAIN THRESHOLD; REVIEW; SCIATIC NERVE; SEX SPECIFIC PAIN; STEROIDOGENESIS;

EID: 84902602168     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00174     Document Type: Review

References (72)

1. Akk, G., Shu, H. J., Wang, C., Steinbach, J. H., Zorumski, C. F., Covey, D. F., et al. (2005). Neurosteroid access to the GABAA receptor. J. Neurosci. 25, 11605-11613. doi: 10.1523/jneurosci.4173-05.2005
2. Aouad, M., Charlet, A., Rodeau, J. L., and Poisbeau, P. (2009). Reduction and prevention of vincristine-induced neuropathic pain symptoms by the non-benzodiazepine anxiolytic etifoxine are mediated by 3alpha-reduced neuros-teroids. Pain 147, 54-59. doi: 10.1016/j.pain.2009.08.001
3. Aouad, M., Petit-Demouliere, N., Goumon, Y., and Poisbeau, P. (2014a). Etifoxine stimulates allopregnanolone synthesis in the spinal cord to produce analgesia in experimental mononeuropathy. Eur. J. Pain 18, 258-268. doi: 10.1002/j.1532-2149.2013.00367.x
4. Aouad, M., Petit-Demouliere, N., and Poisbeau, P. (2010). Anti-hyperalgesic/allodynic properties of the non benzodiazepine anxiolytic etifoxine in inflammatory and neuropathic pain models. Proceedings of the 13th world congress of pain (IASP press) 46.
5. Aouad, M., Zell, V., Juif, P. E., Lacaud, A., Goumon, Y., Darbon, P., et al. (2014b). Etifoxine analgesia in experimental monoarthritis: a combined action that protects spinal inhibition and limits central inflammatory processes. Pain 155, 403-412. doi: 10.1016/j.pain.2013.11.003
6. Baulieu, E. E., and Robel, P. (1990). Neurosteroids: a new brain function? J. Steroid Biochem. Mol. Biol. 37, 395-403. doi: 10.1016/0960-0760(90)90490-c
7. Benavides, J., Quarteronet, D., Imbault, F., Malgouris, C., Uzan, A., Renault, C., et al. (1983). Labelling of "peripheral-type" benzodiazepine binding sites in the rat brain by using [3H]PK 11195, an isoquinoline carboxamide derivative: kinetic studies and autoradiographic localization. J. Neurochem. 41, 1744-1750. doi: 10.1111/j.1471-4159.1983.tb00888.x
8. Bordet, T., Buisson, B., Michaud, M., Abitbol, J. L., Marchand, F., Grist, J., et al. (2008). Specific antinociceptive activity of cholest-4-en-3-one, oxime (TRO19622) in experimental models of painful diabetic and chemotherapy-induced neuropathy. J. Pharmacol. Exp. Ther. 326, 623-632. doi: 10.1124/jpet. 108.139410
9. Breton, J. D., Poisbeau, P., and Darbon, P. (2009). Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord. Mol. Pain 5:63. doi: 10.1186/1744-8069-5-63
10. Breton, J. D., Veinante, P., Uhl-Bronner, S., Vergnano, A. M., Freund-Mercier, M. J., Schlichter, R., et al. (2008). Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition. Mol. Pain 4:19. doi: 10.1186/1744-80 69-4-19
11. Brinton, R. D. (2013). Neurosteroids as regenerative agents in the brain: therapeutic implications. Nat. Rev. Endocrinol. 9, 241-250. doi: 10.1038/nrendo. 2013.31
12. Caruso, D., Pesaresi, M., Abbiati, F., Calabrese, D., Giatti, S., Garcia-Segura, L. M., et al. (2013). Comparison of plasma and cerebrospinal fluid levels of neuroactive steroids with their brain, spinal cord and peripheral nerve levels in male and female rats. Psychoneuroendocrinology 38, 2278-2290. doi: 10.1016/j.psyneuen. 2013.04.016
13. Charlet, A., Lasbennes, F., Darbon, P., and Poisbeau, P. (2008). Fast non-genomic effects of progesterone-derived neurosteroids on nociceptive thresholds and pain symptoms. Pain 139, 603-609. doi: 10.1016/j.pain.2008.06.016
14. Chen, Y. H., Wang, J. Y., Zhou, S., and Shoyab, M. (1991). Bovine endozepine potentiates morphine analgesia in mice. Life Sci. 48, PL79-PL83. doi: 10. 1016/0024-3205(91)90129-y
15. Child, K. J., Currie, J. P., Dis, B., Dodds, M. G., Pearce, D. R., and Twissell, D. J. (1971). The pharmacological properties in animals of CT1341-a new steroid anaesthetic agent. Br. J. Anaesth. 43, 2-13. doi: 10.1093/bja/43.1.2-a
16. Cooper, E. J., Johnston, G. A., and Edwards, F. A. (1999). Effects of a naturally occurring neurosteroid on GABAA IPSCs during development in rat hippocam-pal or cerebellar slices. J. Physiol. 521(Pt. 2), 437-449. doi: 10.1111/j.1469-7793. 1999.00437.x
17. Costa, E., and Guidotti, A. (1991). Diazepam binding inhibitor (DBI): a peptide with multiple biological actions. Life Sci. 49, 325-344. doi: 10.1016/0024-3205(91)90440-m
18. Do-Rego, J. L., Mensah-Nyagan, A. G., Feuilloley, M., Ferrara, P., Pelletier, G., and Vaudry, H. (1998). The endozepine triakontatetraneuropeptide diazepam-binding inhibitor [1750] stimulates neurosteroid biosynthesis in the frog hypothalamus. Neuroscience 83, 555-570. doi: 10.1016/s0306-4522(97) 00362-x
19. Frye, C. A., and Duncan, J. E. (1994). Progesterone metabolites, effective at the GABAA receptor complex, attenuate pain sensitivity in rats. Brain Res. 643, 194-203. doi: 10.1016/0006-8993(94)90025-6
20. Frye, C. A., Rhodes, M. E., Walf, A., and Harney, J. P. (2002). Testosterone enhances aggression of wild-type mice but not those deficient in type I 5alpha-reductase. Brain Res. 948, 165-170. doi: 10.1016/s0006-8993(02)03076-7
21. Frye, C. A., Walf, A. A., Rhodes, M. E., and Harney, J. P. (2004). Progesterone enhances motor, anxiolytic, analgesic and antidepressive behavior of wild-type mice, but not those deficient in type 1 5 alpha-reductase. Brain Res. 1004, 116-124. doi: 10.1016/j.brainres.2004.01.020
22. Giatti, S., Pesaresi, M., Cavaletti, G., Bianchi, R., Carozzi, V., Lombardi, R., et al. (2009). Neuroprotective effects of a ligand of translocator protein-18 kDa (Ro54864) in experimental diabetic neuropathy. Neuroscience 164, 520-529. doi: 10.1016/j.neuroscience.2009.08.005
23. Girard, C., Liu, S., Cadepond, F., Adams, D., Lacroix, C., Verleye, M., et al. (2008). Etifoxine improves peripheral nerve regeneration and functional recovery. Proc. Natl. Acad. Sci. U S A 105, 20505-20510. doi: 10.1073/pnas.08112 01106
24. Greenspan, J. D., Craft, R. M., LeResche, L., Arendt-Nielsen, L., Berkley, K. J., Fillingim, R. B., et al. (2007). Studying sex and gender differences in pain and analgesia: a consensus report. Pain 132(Suppl. 1), S26-S45. doi: 10.1016/j.pain. 2007.10.014
25. Gulinello, M., and Smith, S. S. (2003). Anxiogenic effects of neurosteroid exposure: sex differences and altered GABAA receptor pharmacology in adult rats. J. Pharmacol. Exp. Ther. 305, 541-548. doi: 10.1124/jpet.102.045120
26. Hamon, A., Morel, A., Hue, B., Verleye, M., and Gillardin, J. M. (2003). The modulatory effects of the anxiolytic etifoxine on GABA(A) receptors are mediated by the beta subunit. Neuropharmacology 45, 293-303. doi: 10.1016/s0028-3908(03)00187-4
27. Harney, S. C., Frenguelli, B. G., and Lambert, J. J. (2003). Phosphorylation influences neurosteroid modulation of synaptic GABAA receptors in rat CA1 and dentate gyrus neurones. Neuropharmacology 45, 873-883. doi: 10.1016/s0028-3908(03)00251-x
28. Harrison, N. L., and Simmonds, M. A. (1984). Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res. 323, 287-292. doi: 10.1016/0006-8993(84)90299-3
29. Hernstadt, H., Wang, S., Lim, G., and Mao, J. (2009). Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis. Brain Res. 1286, 42-52. doi: 10.1016/j.brainres.2009.06.043
30. Hosie, A. M., Wilkins, M. E., da Silva, H. M., and Smart, T. G. (2006). Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature 444, 486-489. doi: 10.1038/nature05324
31. Inquimbert, P., Rodeau, J. L., and Schlichter, R. (2008). Regional differences in the decay kinetics of GABA(A) receptor-mediated miniature IPSCs in the dorsal horn of the rat spinal cord are determined by mitochondrial transport of cholesterol. J. Neurosci. 28, 3427-3437. doi: 10.1523/JNEUROSCI.5076-07.2008
32. Itzhak, Y., Baker, L., and Norenberg, M. D. (1993). Characterization of the peripheral-type benzodiazepine receptors in cultured astrocytes: evidence for multiplicity. Glia 9, 211-218. doi: 10.1002/glia.440090306
33. Juif, P. E., Breton, J. D., Rajalu, M., Charlet, A., Goumon, Y., and Poisbeau, P. (2013). Long-lasting spinal oxytocin analgesia is ensured by the stimulation of allopregnanolone synthesis which potentiates GABA(A) receptor-mediated synaptic inhibition. J. Neurosci. 33, 16617-16626. doi: 10.1523/JNEUROSCI. 3084-12.2013
34. Karchewski, L. A., Bloechlinger, S., and Woolf, C. J. (2004). Axonal injury-dependent induction of the peripheral benzodiazepine receptor in small-diameter adult rat primary sensory neurons. Eur. J. Neurosci. 20, 671-683. doi: 10.1111/j.1460-9568.2004.03530.x
35. Kavaliers, M., and Hirst, M. (1986). An octadecaneuropeptide (ODN) derived from diazepam binding inhibitor increases aggressive interactions in mice. Brain Res. 383, 343-349. doi: 10.1016/0006-8993(86)90037-5
36. Kavaliers, M., and Wiebe, J. P. (1987). Analgesic effects of the progesterone metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one and possible modes of action in mice. Brain Res. 415, 393-398. doi: 10.1016/0006-8993(87)90228-9
37. Keller, A. F. (2002). "Synaptic plasticity of inhibitory controls during postnatal development and inflammatory pain states in the rat spinal nociceptive system," in Health and Life Sciences, (Strasbourg: University of Strasbourg Press), 161. (PUS; Thesis.fr).
38. Keller, A. F., Breton, J. D., Schlichter, R., and Poisbeau, P. (2004). Production of 5alpha-reduced neurosteroids is developmentally regulated and shapes GABA(A) miniature IPSCs in lamina II of the spinal cord. J. Neurosci. 24, 907-915. doi: 10.1523/jneurosci.4642-03.2004
39. Keller, A. F., Coull, J. A., Chery, N., Poisbeau, P., and De Koninck, Y. (2001). Region-specific developmental specialization of GABA-glycine cosynapses in laminas I-II of the rat spinal dorsal horn. J. Neurosci. 21, 7871-7880.
40. Lacor, P., Benavides, J., and Ferzaz, B. (1996). Enhanced expression of the peripheral benzodiazepine receptor (PBR) and its endogenous ligand octadecaneuropep-tide (ODN) in the regenerating adult rat sciatic nerve. Neurosci. Lett. 220, 61-65. doi: 10.1016/s0304-3940(96)13187-6
41. Melcangi, R. C., Giatti, S., Pesaresi, M., Calabrese, D., Mitro, N., Caruso, D., et al. (2011). Role of neuroactive steroids in the peripheral nervous system. Front. Endocrinol. (Lausanne) 2:104. doi: 10.3389/fendo.2011.00104
42. Meyer, L., Patte-Mensah, C., Taleb, O., and Mensah-Nyagan, A. G. (2011). Allo-pregnanolone prevents and suppresses oxaliplatin-evoked painful neuropathy: multi-parametric assessment and direct evidence. Pain 152, 170-181. doi: 10. 1016/j.pain.2010.10.015
43. Meyer, L., Venard, C., Schaeffer, V., Patte-Mensah, C., and Mensah-Nyagan, A. G. (2008). The biological activity of 3alpha-hydroxysteroid oxido-reductase in the spinal cord regulates thermal and mechanical pain thresholds after sciatic nerve injury. Neurobiol. Dis. 30, 30-41. doi: 10.1016/j.nbd.2007. 12.001
44. Micallef, J., Soubrouillard, C., Guet, F., Le Guern, M. E., Alquier, C., Bruguerolle, B., et al. (2001). A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected]. Fundam. Clin. Pharmacol. 15, 209-216. doi: 10.1046/j.1472-8206. 2001.00025.x
45. Miller, T. R., Wetter, J. B., Jarvis, M. F., and Bitner, R. S. (2013). Spinal microglial activation in rat models of neuropathic and osteoarthritic pain: an autoradio-graphic study using [3H]PK11195. Eur. J. Pain 17, 692-703. doi: 10.1002/j.1532-2149.2012.00232.x
46. Moynagh, P. N., Bailey, C. J., Boyce, S. J., and Williams, D. C. (1991). Immuno-logical studies on the rat peripheral-type benzodiazepine acceptor. Biochem. J. 275(Pt. 2), 419-425.
47. Nguyen, N., Fakra, E., Pradel, V., Jouve, E., Alquier, C., Le Guern, M. E., et al. (2006). Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: a double-blind controlled study in general practice. Hum. Psychopharmacol. 21, 139-149. doi: 10.1002/hup.814
48. Papadopoulos, V., Berkovich, A., Krueger, K. E., Costa, E., and Guidotti, A. (1991). Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. Endocrinology 129, 1481-1488. doi: 10.1210/endo-129-3-1481
49. Park, C. H., Carboni, E., Wood, P. L., and Gee, K. W. (1996). Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line. Glia 16, 65-70. doi: 10.1002/(sici)1098-1136(199601)16:1<65::aid-glia7>3.0.co;2-a
50. Pathirathna, S., Brimelow, B. C., Jagodic, M. M., Krishnan, K., Jiang, X., Zorumski, C. F., et al. (2005). 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, 429-443. doi: 10.1016/j.pain.2005. 01.009
51. Patte-Mensah, C., Kibaly, C., and Mensah-Nyagan, A. G. (2005). 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, 9044-9049. doi: 10.1073/pnas.0502968102
52. Pednekar, J. R., and Mulgaonker, V. K. (1995). Role of testosterone on pain threshold in rats. Indian J. Physiol. Pharmacol. 39, 423-424.
53. Poisbeau, P., Feltz, P., and Schlichter, R. (1997). Modulation of GABAA receptor-mediated IPSCs by neuroactive steroids in a rat hypothalamo-hypophyseal coculture model. J. Physiol. 500(Pt. 2), 475-485.
54. Poisbeau, P., Patte-Mensah, C., Keller, A. F., Barrot, M., Breton, J. D., Luis-Delgado, O. E., et al. (2005). Inflammatory pain upregulates spinal inhibition via endogenous neurosteroid production. J. Neurosci. 25, 11768-11776. doi: 10. 1523/jneurosci.3841-05.2005
55. Roglio, I., Bianchi, R., Gotti, S., Scurati, S., Giatti, S., Pesaresi, M., et al. (2008). Neuroprotective effects of dihydroprogesterone and progesterone in an experimental model of nerve crush injury. Neuroscience 155, 673-685. doi: 10.1016/j. neuroscience.2008.06.034
56. Rupprecht, R., Rammes, G., Eser, D., Baghai, T. C., Schüle, C., Nothdurfter, C., et al. (2009). Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects. Science 325, 490-493. doi: 10.1126/science. 1175055
57. Rupprecht, R., Papadopoulos, V., Rammes, G., Baghai, T. C., Fan, J., Akula, N., et al. (2010). Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat. Rev. Drug Discov. 9, 971-988. doi: 10.1038/nrd3295
58. Schlichter, R., Keller, A. F., De Roo, M., Breton, J. D., Inquimbert, P., and Poisbeau, P. (2006). Fast nongenomic effects of steroids on synaptic transmission and role of endogenous neurosteroids in spinal pain pathways. J. Mol. Neurosci. 28, 33-51. doi: 10.1385/jmn:28:1:33
59. Schlichter, R., Rybalchenko, V., Poisbeau, P., Verleye, M., and Gillardin, J. (2000). Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine. Neuropharmacology 39, 1523-1535. doi: 10.1016/s0028-3908(99)00253-1
60. Schumacher, M., Weill-Engerer, S., Liere, P., Robert, F., Franklin, R. J., Garcia-Segura, L. M., et al. (2003). Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog. Neurobiol. 71, 3-29. doi: 10. 1016/j.pneurobio.2003.09.004
61. Selye, H. (1941). Anaesthetic effects of steroid hormones. Proc. Soc. Exp. Biol. 46, 116-121. doi: 10.3181/00379727-46-11907
62. Servant, D., Graziani, P. L., Moyse, D., and Parquet, P. J. (1998). Treatment of adjustment disorder with anxiety: efficacy and tolerance of etifoxine in a double-blind controlled study. Encephale 24, 569-574.
63. Smith, S. S. (2001). Pre-menstrual steroids. Cell. Mol. Life Sci. 58, 1263-1275. doi: 10.1007/pl00000938
64. Smith, S. S. (2002). Withdrawal properties of a neuroactive steroid: implications for GABA(A) receptor gene regulation in the brain and anxiety behavior. Steroids 67, 519-528. doi: 10.1016/s0039-128x(01)00170-2
65. Tsuda, M., Inoue, K., and Salter, M. W. (2005). Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia. Trends Neurosci. 28, 101-107. doi: 10.1016/j.tins.2004.12.002
66. Varga, B., Marko, K., Hadinger, N., Jelitai, M., Demeter, K., Tihanyi, K., et al. (2009). Translocator protein (TSPO 18kDa) is expressed by neural stem and neuronal precursor cells. Neurosci. Lett. 462, 257-262. doi: 10.1016/j.neulet. 2009.06.051
67. Vergnano, A. M., Schlichter, R., and Poisbeau, P. (2007). PKC activation sets an upper limit to the functional plasticity of GABAergic transmission induced by endogenous neurosteroids. Eur. J. Neurosci. 26, 1173-1182. doi: 10.1111/j.1460-9568.2007.05746.x
68. Verleye, M., Akwa, Y., Liere, P., Ladurelle, N., Pianos, A., Eychenne, B., et al. (2005). The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain. Pharmacol. Biochem. Behav. 82, 712-720. doi: 10.1016/j.pbb.2005.11.013
69. Verleye, M., Pansart, Y., and Gillardin, J. (2002). Effects of etifoxine on ligand binding to GABA(A) receptors in rodents. Neurosci. Res. 44, 167-172. doi: 10. 1016/s0168-0102(02)00121-9
70. Verleye, M., Schlichter, R., and Gillardin, J. M. (1999). Interactions of etifoxine with the chloride channel coupled to the GABA(A) receptor complex. Neuroreport 10, 3207-3210. doi: 10.1097/00001756-199910190-00015
71. Wang, W., Wu, D. C., Chen, Y. H., He, W., and Yu, L. C. (2002). Anti-nociceptive effects of diazepam binding inhibitor in the central nervous system of rats. Brain Res. 956, 393-397. doi: 10.1016/s0006-8993(02) 03613-2
72. Zeilhofer, H. U. (2009). Etifoxine (Stresam) for chemotherapy-induced pain? Pain 147, 9-10. doi: 10.1016/j.pain.2009.09.021