NMDA receptor activation induces long-term potentiation of glycine synapses

Autoři: Michelle L. Kloc aff001;  Bruno Pradier aff001;  Anda M. Chirila aff001;  Julie A. Kauer aff001
Působiště autorů: Dept. of Pharmacology, Physiology and Biotechnology, Brown Institute for Brain Science, Brown University, Providence, RI, United States of America aff001
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222066


Of the fast ionotropic synapses, glycinergic synapses are the least well understood, but are vital for the maintenance of inhibitory signaling in the brain and spinal cord. Glycinergic signaling comprises half of the inhibitory signaling in the spinal cord, and glycinergic synapses are likely to regulate local nociceptive processing as well as the transmission to the brain of peripheral nociceptive information. Here we have investigated the rapid and prolonged potentiation of glycinergic synapses in the superficial dorsal horn of young male and female mice after brief activation of NMDA receptors (NMDARs). Glycinergic inhibitory postsynaptic currents (IPSCs) evoked with lamina II-III stimulation in identified GABAergic neurons in lamina II were potentiated by bath-applied Zn2+ and were depressed by the prostaglandin PGE2, consistent with the presence of both GlyRα1- and GlyRα3-containing receptors. NMDA application rapidly potentiated synaptic glycinergic currents. Whole-cell currents evoked by exogenous glycine were also readily potentiated by NMDA, indicating that the potentiation results from altered numbers or conductance of postsynaptic glycine receptors. Repetitive depolarization alone of the postsynaptic GABAergic neuron also potentiated glycinergic synapses, and intracellular EGTA prevented both NMDA-induced and depolarization-induced potentiation of glycinergic IPSCs. Optogenetic activation of trpv1 lineage afferents also triggered NMDAR-dependent potentiation of glycinergic synapses. Our results suggest that during peripheral injury or inflammation, nociceptor firing during injury is likely to potentiate glycinergic synapses on GABAergic neurons. This disinhibition mechanism may be engaged rapidly, altering dorsal horn circuitry to promote the transmission of nociceptive information to the brain.

Klíčová slova:

Biology and life sciences – Cell biology – Cellular types – Animal cells – Afferent neurons – Signal transduction – Sensory receptors – Nociceptors – Neuroscience – Cellular neuroscience – Neurons – Synapses – Sensory perception – Anatomy – Nervous system – Physiology – Electrophysiology – Neurophysiology – Membrane potential – Depolarization – Biochemistry – Proteins – Amino acids – Aliphatic amino acids – Glycine – Psychology – Medicine and health sciences – Neuroanatomy – Immunology – Immune response – Inflammation – Diagnostic medicine – Signs and symptoms – Pathology and laboratory medicine – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Organic chemistry – Social sciences


1. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895–926. Epub 2009/08/29. doi: 10.1016/j.jpain.2009.06.012 19712899; PubMed Central PMCID: PMC2750819.

2. Torsney C, MacDermott AB. Disinhibition opens the gate to pathological pain signaling in superficial neurokinin 1 receptor-expressing neurons in rat spinal cord. J Neurosci. 2006;26(6):1833–43. Epub 2006/02/10. doi: 10.1523/JNEUROSCI.4584-05.2006 16467532.

3. Baldo BA, Daniel RA, Berridge CW, Kelley AE. Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol. 2003;464(2):220–37. doi: 10.1002/cne.10783 12898614.

4. Zeilhofer HU, Benke D, Yevenes GE. Chronic pain States: pharmacological strategies to restore diminished inhibitory spinal pain control. Annu Rev Pharmacol Toxicol. 2012;52:111–33. doi: 10.1146/annurev-pharmtox-010611-134636 21854227.

5. Zeilhofer HU, Wildner H, Yevenes GE. Fast synaptic inhibition in spinal sensory processing and pain control. Physiol Rev. 2012;92(1):193–235. doi: 10.1152/physrev.00043.2010 22298656.

6. Yaksh TL. Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. Pain. 1989;37(1):111–23. Epub 1989/04/01. doi: 10.1016/0304-3959(89)90160-7 2542867.

7. Woolf CJ, Shortland P, Sivilotti LG. Sensitization of high mechanothreshold superficial dorsal horn and flexor motor neurones following chemosensitive primary afferent activation. Pain. 1994;58(2):141–55. Epub 1994/08/01. doi: 10.1016/0304-3959(94)90195-3 7816483.

8. Baba H, Ji RR, Kohno T, Moore KA, Ataka T, Wakai A, et al. Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn. Mol Cell Neurosci. 2003;24(3):818–30. Epub 2003/12/11. 14664828.

9. Altschuler RA, Betz H, Parakkal MH, Reeks KA, Wenthold RJ. Identification of glycinergic synapses in the cochlear nucleus through immunocytochemical localization of the postsynaptic receptor. Brain Res. 1986;369(1–2):316–20. doi: 10.1016/0006-8993(86)90542-1 3008938.

10. Alvarez FJ, Dewey DE, Harrington DA, Fyffe RE. Cell-type specific organization of glycine receptor clusters in the mammalian spinal cord. J Comp Neurol. 1997;379(1):150–70. 9057118.

11. Foster E, Wildner H, Tudeau L, Haueter S, Ralvenius WT, Jegen M, et al. Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch. Neuron. 2015;85(6):1289–304. Epub 2015/03/20. doi: 10.1016/j.neuron.2015.02.028 25789756; PubMed Central PMCID: PMC4372258.

12. 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(6951):938–42. doi: 10.1038/nature01868 12931188.

13. 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(1):169–79. Epub 1994/07/01. doi: 10.1152/jn.1994.72.1.169 7965003.

14. Zeilhofer HU. Loss of glycinergic and GABAergic inhibition in chronic pain—contributions of inflammation and microglia. Int Immunopharmacol. 2008;8(2):182–7. Epub 2008/01/10. doi: 10.1016/j.intimp.2007.07.009 18182224.

15. Huang X, Shaffer PL, Ayube S, Bregman H, Chen H, Lehto SG, et al. Crystal structures of human glycine receptor alpha3 bound to a novel class of analgesic potentiators. Nat Struct Mol Biol. 2017;24(2):108–13. Epub 2016/12/20. doi: 10.1038/nsmb.3329 27991902.

16. Takazawa T, Choudhury P, Tong CK, Conway CM, Scherrer G, Flood PD, et al. Inhibition Mediated by Glycinergic and GABAergic Receptors on Excitatory Neurons in Mouse Superficial Dorsal Horn Is Location-Specific but Modified by Inflammation. J Neurosci. 2017;37(9):2336–48. Epub 2017/01/29. doi: 10.1523/JNEUROSCI.2354-16.2017 28130358; PubMed Central PMCID: PMC5354347.

17. Takazawa T, MacDermott AB. Glycinergic and GABAergic tonic inhibition fine tune inhibitory control in regionally distinct subpopulations of dorsal horn neurons. J Physiol. 2010;588(Pt 14):2571–87. Epub 2010/05/26. doi: 10.1113/jphysiol.2010.188292 20498232; PubMed Central PMCID: PMC2916989.

18. Tyagarajan SK, Fritschy JM. Gephyrin: a master regulator of neuronal function? Nat Rev Neurosci. 2014;15(3):141–56. Epub 2014/02/21. doi: 10.1038/nrn3670 24552784.

19. Harvey RJ, Depner UB, Wassle H, Ahmadi S, Heindl C, Reinold H, et al. GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science. 2004;304(5672):884–7. Epub 2004/05/08. doi: 10.1126/science.1094925 15131310.

20. Becker CM, Hoch W, Betz H. Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J. 1988;7(12):3717–26. 2850172; PubMed Central PMCID: PMC454946.

21. Malosio ML, Marqueze-Pouey B, Kuhse J, Betz H. Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J. 1991;10(9):2401–9. Epub 1991/09/01. 1651228; PubMed Central PMCID: PMC452935.

22. Randic M, Jiang MC, Cerne R. Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord. J Neurosci. 1993;13(12):5228–41. Epub 1993/12/01. 8254370.

23. Ikeda H, Heinke B, Ruscheweyh R, Sandkuhler J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science. 2003;299(5610):1237–40. Epub 2003/02/22. doi: 10.1126/science.1080659 12595694.

24. Liu XG, Sandkuhler J. Long-term potentiation of C-fiber-evoked potentials in the rat spinal dorsal horn is prevented by spinal N-methyl-D-aspartic acid receptor blockage. Neurosci Lett. 1995;191(1–2):43–6. Epub 1995/05/19. doi: 10.1016/0304-3940(95)11553-0 7659287.

25. Fenselau H, Heinke B, Sandkuhler J. Heterosynaptic long-term potentiation at GABAergic synapses of spinal lamina I neurons. J Neurosci. 2011;31(48):17383–91. Epub 2011/12/02. doi: 10.1523/JNEUROSCI.3076-11.2011 22131400; PubMed Central PMCID: PMC6623805.

26. Chirila AM, Brown TE, Bishop RA, Bellono NW, Pucci FG, Kauer JA. Long-term potentiation of glycinergic synapses triggered by interleukin 1beta. Proc Natl Acad Sci U S A. 2014;111(22):8263–8. Epub 2014/05/17. doi: 10.1073/pnas.1401013111 24830427; PubMed Central PMCID: PMC4050559.

27. Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, et al. Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature. 2001;410(6827):471–5. Epub 2001/03/22. doi: 10.1038/35068566 11260714.

28. Whitehead KJ, Smith CG, Delaney SA, Curnow SJ, Salmon M, Hughes JP, et al. Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury. Brain Behav Immun. 2010;24(4):569–76. Epub 2009/12/29. doi: 10.1016/j.bbi.2009.12.007 20035858.

29. Raghavendra V, Tanga FY, DeLeo JA. Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci. 2004;20(2):467–73. Epub 2004/07/06. doi: 10.1111/j.1460-9568.2004.03514.x 15233755.

30. Xu TL, Dong XP, Wang DS. N-methyl-D-aspartate enhancement of the glycine response in the rat sacral dorsal commissural neurons. Eur J Neurosci. 2000;12(5):1647–53. Epub 2000/05/03. doi: 10.1046/j.1460-9568.2000.00065.x 10792442.

31. Levi S, Schweizer C, Bannai H, Pascual O, Charrier C, Triller A. Homeostatic regulation of synaptic GlyR numbers driven by lateral diffusion. Neuron. 2008;59(2):261–73. doi: 10.1016/j.neuron.2008.05.030 18667154.

32. Fucile S, De Saint Jan D, de Carvalho LP, Bregestovski P. Fast potentiation of glycine receptor channels of intracellular calcium in neurons and transfected cells. Neuron. 2000;28(2):571–83. Epub 2001/01/06. doi: 10.1016/s0896-6273(00)00134-3 11144365.

33. Mainen ZF, Maletic-Savatic M, Shi SH, Hayashi Y, Malinow R, Svoboda K. Two-photon imaging in living brain slices. Methods. 1999;18(2):231–9, 181. Epub 1999/06/05. doi: 10.1006/meth.1999.0776 10356355.

34. Ting JT, Daigle TL, Chen Q, Feng G. Acute brain slice methods for adult and aging animals: application of targeted patch clamp analysis and optogenetics. Methods Mol Biol. 2014;1183:221–42. Epub 2014/07/16. doi: 10.1007/978-1-4939-1096-0_14 25023312; PubMed Central PMCID: PMC4219416.

35. Lynch JW, Jacques P, Pierce KD, Schofield PR. Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways. J Neurochem. 1998;71(5):2159–68. Epub 1998/11/03. doi: 10.1046/j.1471-4159.1998.71052159.x 9798943.

36. Miller PS, Da Silva HM, Smart TG. Molecular basis for zinc potentiation at strychnine-sensitive glycine receptors. J Biol Chem. 2005;280(45):37877–84. Epub 2005/09/08. doi: 10.1074/jbc.M508303200 16144831.

37. Staubli U, Larson J, Lynch G. Mossy fiber potentiation and long-term potentiation involve different expression mechanisms. Synapse. 1990;5(4):333–5. Epub 1990/01/01. doi: 10.1002/syn.890050410 2360200.

38. Zalutsky RA, Nicoll RA. Comparison of two forms of long-term potentiation in single hippocampal neurons. Science. 1990;248(4963):1619–24. Epub 1990/06/29. doi: 10.1126/science.2114039 2114039.

39. Salin PA, Scanziani M, Malenka RC, Nicoll RA. Distinct short-term plasticity at two excitatory synapses in the hippocampus. Proc Natl Acad Sci U S A. 1996;93(23):13304–9. Epub 1996/11/12. doi: 10.1073/pnas.93.23.13304 8917586; PubMed Central PMCID: PMC24088.

40. Malenka RC, Kauer JA, Zucker RS, Nicoll RA. Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission. Science. 1988;242(4875):81–4. Epub 1988/10/07. doi: 10.1126/science.2845577 2845577.

41. Herring BE, Nicoll RA. Long-Term Potentiation: From CaMKII to AMPA Receptor Trafficking. Annu Rev Physiol. 2016;78:351–65. Epub 2016/02/11. doi: 10.1146/annurev-physiol-021014-071753 26863325.

42. Wyllie DJ, Nicoll RA. A role for protein kinases and phosphatases in the Ca(2+)-induced enhancement of hippocampal AMPA receptor-mediated synaptic responses. Neuron. 1994;13(3):635–43. Epub 1994/09/01. doi: 10.1016/0896-6273(94)90031-0 7917294.

43. Gutlerner JL, Penick EC, Snyder EM, Kauer JA. Novel protein kinase A-dependent long-term depression of excitatory synapses. Neuron. 2002;36(5):921–31. Epub 2002/12/07. doi: 10.1016/s0896-6273(02)01051-6 12467595.

44. Pradier B, Shin HB, Kim DS, St Laurent R, Lipscombe D, Kauer JA. Long-Term Depression Induced by Optogenetically Driven Nociceptive Inputs to Trigeminal Nucleus Caudalis or Headache Triggers. J Neurosci. 2018;38(34):7529–40. Epub 2018/07/29. doi: 10.1523/JNEUROSCI.3032-17.2018 30054391; PubMed Central PMCID: PMC6104302.

45. Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, et al. Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci. 2011;31(13):5067–77. Epub 2011/04/01. doi: 10.1523/JNEUROSCI.6451-10.2011 21451044; PubMed Central PMCID: PMC3087977.

46. Puig S, Sorkin LS. Formalin-evoked activity in identified primary afferent fibers: systemic lidocaine suppresses phase-2 activity. Pain. 1996;64(2):345–55. Epub 1996/02/01. doi: 10.1016/0304-3959(95)00121-2(95)00121-2. 8740613.

47. Peirs C, Seal RP. Neural circuits for pain: Recent advances and current views. Science. 2016;354(6312):578–84. Epub 2016/11/05. doi: 10.1126/science.aaf8933 27811268.

48. Todd AJ. Identifying functional populations among the interneurons in laminae I-III of the spinal dorsal horn. Mol Pain. 2017;13:1744806917693003. Epub 2017/03/23. doi: 10.1177/1744806917693003 28326935; PubMed Central PMCID: PMC5315367.

49. Yasaka T, Tiong SY, Hughes DI, Riddell JS, Todd AJ. Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach. Pain. 2010;151(2):475–88. Epub 2010/09/08. doi: 10.1016/j.pain.2010.08.008 20817353; PubMed Central PMCID: PMC3170912.

50. Heinke B, Ruscheweyh R, Forsthuber L, Wunderbaldinger G, Sandkuhler J. Physiological, neurochemical and morphological properties of a subgroup of GABAergic spinal lamina II neurones identified by expression of green fluorescent protein in mice. J Physiol. 2004;560(Pt 1):249–66. Epub 2004/07/31. doi: 10.1113/jphysiol.2004.070540 15284347; PubMed Central PMCID: PMC1665197.

51. Punnakkal P, von Schoultz C, Haenraets K, Wildner H, Zeilhofer HU. Morphological, biophysical and synaptic properties of glutamatergic neurons of the mouse spinal dorsal horn. J Physiol. 2014;592(4):759–76. Epub 2013/12/11. doi: 10.1113/jphysiol.2013.264937 24324003; PubMed Central PMCID: PMC3934713.

52. Nowak A, Mathieson HR, Chapman RJ, Janzso G, Yanagawa Y, Obata K, et al. Kv3.1b and Kv3.3 channel subunit expression in murine spinal dorsal horn GABAergic interneurones. J Chem Neuroanat. 2011;42(1):30–8. Epub 2011/03/29. doi: 10.1016/j.jchemneu.2011.02.003 21440618; PubMed Central PMCID: PMC3161392.

53. Cui L, Kim YR, Kim HY, Lee SC, Shin HS, Szabo G, et al. Modulation of synaptic transmission from primary afferents to spinal substantia gelatinosa neurons by group III mGluRs in GAD65-EGFP transgenic mice. J Neurophysiol. 2011;105(3):1102–11. doi: 10.1152/jn.00108.2010 21177998.

54. Patrizio A, Renner M, Pizzarelli R, Triller A, Specht CG. Alpha subunit-dependent glycine receptor clustering and regulation of synaptic receptor numbers. Sci Rep. 2017;7(1):10899. Epub 2017/09/09. doi: 10.1038/s41598-017-11264-3 28883437; PubMed Central PMCID: PMC5589798.

55. Charrier C, Machado P, Tweedie-Cullen RY, Rutishauser D, Mansuy IM, Triller A. A crosstalk between beta1 and beta3 integrins controls glycine receptor and gephyrin trafficking at synapses. Nat Neurosci. 2010;13(11):1388–95. doi: 10.1038/nn.2645 20935643.

56. Specht CG, Grunewald N, Pascual O, Rostgaard N, Schwarz G, Triller A. Regulation of glycine receptor diffusion properties and gephyrin interactions by protein kinase C. Embo J. 2011;30(18):3842–53. doi: 10.1038/emboj.2011.276 21829170.

57. Elias GM, Nicoll RA. Synaptic trafficking of glutamate receptors by MAGUK scaffolding proteins. Trends Cell Biol. 2007;17(7):343–52. Epub 2007/07/24. doi: 10.1016/j.tcb.2007.07.005 17644382.

58. Lee H, Kameyama K, Huganir RL, Bear MF. NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron. 1998;21:1151–62. doi: 10.1016/s0896-6273(00)80632-7 9856470

59. Sharma K, Fong DK, Craig AM. Postsynaptic protein mobility in dendritic spines: long-term regulation by synaptic NMDA receptor activation. Mol Cell Neurosci. 2006;31(4):702–12. Epub 2006/03/01. doi: 10.1016/j.mcn.2006.01.010 16504537.

60. Moreau AW, Kullmann DM. NMDA receptor-dependent function and plasticity in inhibitory circuits. Neuropharmacology. 2013;74:23–31. Epub 2013/03/30. doi: 10.1016/j.neuropharm.2013.03.004 23537500.

61. Marsden KC, Beattie JB, Friedenthal J, Carroll RC. NMDA receptor activation potentiates inhibitory transmission through GABA receptor-associated protein-dependent exocytosis of GABA(A) receptors. J Neurosci. 2007;27(52):14326–37. Epub 2007/12/28. doi: 10.1523/JNEUROSCI.4433-07.2007 18160640.

62. Bannai H, Levi S, Schweizer C, Inoue T, Launey T, Racine V, et al. Activity-dependent tuning of inhibitory neurotransmission based on GABAAR diffusion dynamics. Neuron. 2009;62(5):670–82. doi: 10.1016/j.neuron.2009.04.023 19524526.

63. Bannai H, Niwa F, Sherwood MW, Shrivastava AN, Arizono M, Miyamoto A, et al. Bidirectional Control of Synaptic GABAAR Clustering by Glutamate and Calcium. Cell reports. 2015;13(12):2768–80. doi: 10.1016/j.celrep.2015.12.002 26711343; PubMed Central PMCID: PMC4700050.

64. Petrini EM, Ravasenga T, Hausrat TJ, Iurilli G, Olcese U, Racine V, et al. Synaptic recruitment of gephyrin regulates surface GABAA receptor dynamics for the expression of inhibitory LTP. Nat Commun. 2014;5:3921. Epub 2014/06/05. doi: 10.1038/ncomms4921 24894704; PubMed Central PMCID: PMC4059940.

65. Yamanaka I, Miki M, Asakawa K, Kawakami K, Oda Y, Hirata H. Glycinergic transmission and postsynaptic activation of CaMKII are required for glycine receptor clustering in vivo. Genes Cells. 2013;18(3):211–24. Epub 2013/01/26. doi: 10.1111/gtc.12032 23347046.

66. Kirsch J, Betz H. Glycine-receptor activation is required for receptor clustering in spinal neurons. Nature. 1998;392(6677):717–20. Epub 1998/05/16. doi: 10.1038/33694 9565032.

67. Kurotani T, Yamada K, Yoshimura Y, Crair MC, Komatsu Y. State-dependent bidirectional modification of somatic inhibition in neocortical pyramidal cells. Neuron. 2008;57(6):905–16. Epub 2008/03/28. doi: 10.1016/j.neuron.2008.01.030 18367091; PubMed Central PMCID: PMC2880402.

68. Lu Y, Dong H, Gao Y, Gong Y, Ren Y, Gu N, et al. A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia. J Clin Invest. 2013;123(9):4050–62. Epub 2013/08/28. doi: 10.1172/JCI70026 23979158.

69. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150(3699):971–9. Epub 1965/11/19. doi: 10.1126/science.150.3699.971 5320816.

70. Laird JM, Bennett GJ. Dorsal root potentials and afferent input to the spinal cord in rats with an experimental peripheral neuropathy. Brain Res. 1992;584(1–2):181–90. Epub 1992/07/03. doi: 10.1016/0006-8993(92)90893-e 1515937.

71. Ibuki T, Hama AT, Wang XT, Pappas GD, Sagen J. Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts. Neuroscience. 1997;76(3):845–58. Epub 1997/02/01. doi: 10.1016/s0306-4522(96)00341-7 9135056.

72. Moore KA, Kohno T, Karchewski LA, Scholz J, Baba H, Woolf CJ. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci. 2002;22(15):6724–31. Epub 2002/08/02. doi: 20026611 12151551.

73. Muller F, Heinke B, Sandkuhler J. Reduction of glycine receptor-mediated miniature inhibitory postsynaptic currents in rat spinal lamina I neurons after peripheral inflammation. Neuroscience. 2003;122(3):799–805. Epub 2003/11/19. doi: 10.1016/j.neuroscience.2003.07.009 14622922.

74. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–15. Epub 2010/10/22. doi: 10.1016/j.pain.2010.09.030 20961685; PubMed Central PMCID: PMC3268359.

75. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012;73(4):638–52. Epub 2012/03/01. doi: 10.1016/j.neuron.2012.02.008 22365541; PubMed Central PMCID: PMC3319438.

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