PAIN
Volume 147, Issue 1 , Pages 54-59 , 15 December 2009

Reduction and prevention of vincristine-induced neuropathic pain symptoms by the non-benzodiazepine anxiolytic etifoxine are mediated by 3α-reduced neurosteroids

Received 22 May 2009 ,Revised 16 July 2009 ,Accepted 5 August 2009.

References 

  1. Authier N, Coudore F, Eschalier A, Fialip J. Pain related behaviour during vincristine-induced neuropathy in rats. Neuroreport. 1999;10:965–968
  2. Belelli D, Lambert JJ. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci. 2005;6:565–575
  3. Boissier JR, Simon P, Zaczinska M, Fichelle J. Experimental psychopharmacologic study of a new psychotropic drug, 2-ethylamino-6-chloro-4-methyl-4-phenyl-4H-3,1-benzoxazine. Therapie. 1972;27:325–338
  4. Bordet T, Buisson B, Michaud M, Abitbol JL, Marchand F, Grist J, et al. 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. 2008;326:623–632
  5. Casey EB, Jellife AM, Le Quesne PM, Millett YL. Vincristine neuropathy. Clinical and electrophysiological observations. Brain. 1973;96:69–86
  6. Charlet A, Lasbennes F, Darbon P, Poisbeau P. Fast non-genomic effects of progesterone-derived neurosteroids on nociceptive thresholds and pain symptoms. Pain. 2008;139:603–609
  7. Compagnone NA, Mellon SH. Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol. 2000;21:1–56
  8. Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature. 2003;424:938–942
  9. Craig AD. A new view of pain as a homeostatic emotion. Trends Neurosci. 2003;26:303–307
  10. De Koninck Y. Altered chloride homeostasis in neurological disorders: a new target. Curr Opin Pharmacol. 2007;7:93–99
  11. Flatters SJ, Bennett GJ. Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy. Pain. 2004;109:150–161
  12. Frye CA, Duncan JE. Progesterone metabolites, effective at the GABAA receptor complex, attenuate pain sensitivity in rats. Brain Res. 1994;643:194–203
  13. Girard C, Liu S, Cadepond F, Adams D, Lacroix C, Verleye M, et al. Etifoxine improves peripheral nerve regeneration and functional recovery. Proc Natl Acad Sci USA. 2008;105:20505–20510
  14. Hamon A, Morel A, Hue B, Verleye M, Gillardin JM. The modulatory effects of the anxiolytic etifoxine on GABA(A) receptors are mediated by the beta subunit. Neuropharmacology. 2003;45:293–303
  15. Ishikawa T, Marsala M, Sakabe T, Yaksh TL. Characterization of spinal amino acid release and touch-evoked allodynia produced by spinal glycine or GABA(A) receptor antagonist. Neuroscience. 2000;95:781–786
  16. Jarrell J. Studies on the developmental pattern of rat ovarian 3 alpha-hydroxysteroid dehydrogenase: inhibition of the postpubertal activity with medroxyprogesterone acetate in vivo. J Steroid Biochem. 1984;21:151–156
  17. Jin HW, Flatters SJ, Xiao WH, Mulhern HL, Bennett GJ. Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-l-carnitine: effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells. Exp Neurol. 2008;210:229–237
  18. Keller AF, Breton JD, Schlichter R, Poisbeau P. Production of 5alpha-reduced neurosteroids is developmentally regulated and shapes GABA(A) miniature IPSCs in lamina II of the spinal cord. J Neurosci. 2004;24:907–915
  19. Knabl J, Witschi R, Hosl K, Reinold H, Zeilhofer UB, Ahmadi S, et al. Reversal of pathological pain through specific spinal GABAA receptor subtypes. Nature. 2008;451:330–334
  20. Luis-Delgado OE, Barrot M, Rodeau JL, Schott G, Benbouzid M, Poisbeau P, et al. Calibrated forceps: a sensitive and reliable tool for pain and analgesia studies. J Pain. 2006;7:32–39
  21. 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
  22. Meyer L, Venard C, Schaeffer V, Patte-Mensah C, Mensah-Nyagan AG. The biological activity of 3alpha-hydroxysteroid oxido-reductase in the spinal cord regulates thermal and mechanical pain thresholds after sciatic nerve injury. Neurobiol Dis. 2008;30:30–41
  23. Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapere JJ, Lindemann P, et al. Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 2006;27:402–409
  24. Pathirathna S, Brimelow BC, Jagodic MM, Krishnan K, Jiang X, Zorumski CF, et al. 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. 2005;114:429–443
  25. Pathirathna S, Todorovic SM, Covey DF, Jevtovic-Todorovic V. 5alpha-reduced neuroactive steroids alleviate thermal and mechanical hyperalgesia in rats with neuropathic pain. Pain. 2005;117:326–339
  26. Penning TM, Sharp RB, Krieger NR. Purification and properties of 3 alpha-hydroxysteroid dehydrogenase from rat brain cytosol. Inhibition by nonsteroidal anti-inflammatory drugs and progestins. J Biol Chem. 1985;260:15266–15272
  27. 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
  28. Schlichter R, Keller AF, De Roo M, Breton JD, Inquimbert P, Poisbeau P. Fast nongenomic effects of steroids on synaptic transmission and role of endogenous neurosteroids in spinal pain pathways. J Mol Neurosci. 2006;28:33–51
  29. Schlichter R, Rybalchenko V, Poisbeau P, Verleye M, Gillardin J. Modulation of GABAergic synaptic transmission by the non-benzodiazepine anxiolytic etifoxine. Neuropharmacology. 2000;39:1523–1535
  30. Sivilotti L, Woolf CJ. The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol. 1994;72:169–179
  31. Tanner KD, Levine JD, Topp KS. Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine-induced painful neuropathy in rat. J Comp Neurol. 1998;395:481–492
  32. Tanner KD, Reichling DB, Levine JD. Nociceptor hyper-responsiveness during vincristine-induced painful peripheral neuropathy in the rat. J Neurosci. 1998;18:6480–6491
  33. Topp KS, Tanner KD, Levine JD. Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat. J Comp Neurol. 2000;424:563–576
  34. Ugale RR, Sharma AN, Kokare DM, Hirani K, Subhedar NK, Chopde CT. Neurosteroid allopregnanolone mediates anxiolytic effect of etifoxine in rats. Brain Res. 2007;1184:193–201
  35. Verleye M, Akwa Y, Liere P, Ladurelle N, Pianos A, Eychenne B, et al. The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain. Pharmacol Biochem Behav. 2005;82:712–720
  36. Verleye M, Gillardin JM. Effects of etifoxine on stress-induced hyperthermia, freezing behavior and colonic motor activation in rats. Physiol Behav. 2004;82:891–897
  37. Verleye M, Schlichter R, Gillardin JM. Interactions of etifoxine with the chloride channel coupled to the GABA(A) receptor complex. Neuroreport. 1999;10:3207–3210
  38. Weng HR, Cordella JV, Dougherty PM. Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. Pain. 2003;103:131–138

PII: S0304-3959(09)00448-5

doi: 10.1016/j.pain.2009.08.001

PAIN
Volume 147, Issue 1 , Pages 54-59 , 15 December 2009

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