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Molecular Pain

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Open Access 01-12-2006 | Research

Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain

Authors: Steven A Prescott, Terrence J Sejnowski, Yves De Koninck

Published in: Molecular Pain | Issue 1/2006

Abstract

Background

Reduction of the transmembrane chloride gradient in spinal lamina I neurons contributes to the cellular hyperexcitability producing allodynia and hyperalgesia after peripheral nerve injury. The resultant decrease in anion reversal potential (i.e. shift in E _anion to less negative potentials) reduces glycine/GABA_A receptor-mediated hyperpolarization, but the large increase in membrane conductance caused by inhibitory input can nonetheless shunt concurrent excitatory input. Without knowing the relative contribution of hyperpolarization and shunting to inhibition's modulation of firing rate, it is difficult to predict how much net disinhibition results from reduction of E _anion. We therefore used a biophysically accurate lamina I neuron model to investigate quantitatively how changes in E _anion affect firing rate modulation.

Results

Simulations reveal that even a small reduction of E _anion compromises inhibitory control of firing rate because reduction of E _anion not only decreases glycine/GABA_A receptor-mediated hyperpolarization, but can also indirectly compromise the capacity of shunting to reduce spiking. The latter effect occurs because shunting-mediated modulation of firing rate depends on a competition between two biophysical phenomena: shunting reduces depolarization, which translates into reduced spiking, but shunting also shortens the membrane time constant, which translates into faster membrane charging and increased spiking; the latter effect predominates when average depolarization is suprathreshold. Disinhibition therefore occurs as both hyperpolarization- and shunting-mediated modulation of firing rate are subverted by reduction of E _anion. Small reductions may be compensated for by increased glycine/GABA_A receptor-mediated input, but the system decompensates (i.e. compensation fails) as reduction of E _anion exceeds a critical value. Hyperexcitability necessarily develops once disinhibition becomes incompensable. Furthermore, compensation by increased glycine/GABA_A receptor-mediated input introduces instability into the system, rendering it increasingly prone to abrupt decompensation and even paradoxical excitation.

Conclusion

Reduction of E _anion dramatically compromises the inhibitory control of firing rate and, if compensation fails, is likely to contribute to the allodynia and hyperalgesia associated with neuropathic pain. These data help explain the relative intractability of neuropathic pain and illustrate how it is important to choose therapies not only based on disease mechanism, but based on quantitative understanding of that mechanism.

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Woolf CJ, Salter MW: Neuronal plasticity: increasing the gain in pain. Science 2000, 288: 1765–1769. 10.1126/science.288.5472.1765PubMed

Woolf CJ, Mannion RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999, 353: 1959–1964. 10.1016/S0140-6736(99)01307-0PubMed

Woolf CJ: Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life Sci 2004, 74: 2605–2610. 10.1016/j.lfs.2004.01.003PubMed

Koltzenburg M, Scadding J: Neuropathic pain. Curr Opin Neurol 2001, 14: 641–647. 10.1097/00019052-200110000-00014PubMed

Besson JM: The neurobiology of pain. Lancet 1999, 353: 1610–1615. 10.1016/S0140-6736(99)01313-6PubMed

Dickenson AH: Balances between excitatory and inhibitory events in the spinal cord and chronic pain. Prog Brain Res 1996, 110: 225–231.PubMed

Wiesenfeld-Hallin Z, Aldskogius H, Grant G, Hao JX, Hokfelt T, Xu XJ: Central inhibitory dysfunctions: mechanisms and clinical implications. Behav Brain Sci 1997, 20: 420–425. 10.1017/S0140525X97261480PubMed

Sandkühler J: Neurobiology of spinal nociception: new concepts. Prog Brain Res 1996, 110: 207–224.PubMed

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: 111–123. 10.1016/0304-3959(89)90160-7PubMed

10.

Sherman SE, Loomis CW: Morphine insensitive allodynia is produced by intrathecal strychnine in the lightly anesthetized rat. Pain 1994, 56: 17–29. 10.1016/0304-3959(94)90146-5PubMed

11.

Sivilotti L, Woolf CJ: The contribution of GABA(A) and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol 1994, 72: 169–179.PubMed

12.

Sherman SE, Loomis CW: Strychnine-dependent allodynia in the urethane-anesthetized rat is segmentally distributed and prevented by intrathecal glycine and betaine. Can J Physiol Pharmacol 1995, 73: 1698–1705.PubMed

13.

Sherman SE, Loomis CW: Strychnine-sensitive modulation is selective for non-noxious somatosensory input in the spinal cord of the rat. Pain 1996, 66: 321–330. 10.1016/0304-3959(96)03063-1PubMed

14.

Sorkin LS, Puig S: Neuronal model of tactile allodynia produced by spinal strychnine: effects of excitatory amino acid receptor antagonists and a mu-opiate receptor agonist. Pain 1996, 68: 283–292. 10.1016/S0304-3959(96)03130-2PubMed

15.

Sorkin LS, Puig S, Jones DL: Spinal bicuculline produces hypersensitivity of dorsal horn neurons: effects of excitatory amino acid antagonists. Pain 1998, 77: 181–190. 10.1016/S0304-3959(98)00094-3PubMed

16.

Loomis CW, Khandwala H, Osmond G, Hefferan MP: Coadministration of intrathecal strychnine and bicuculline effects synergistic allodynia in the rat: an isobolographic analysis. J Pharmacol Exp Ther 2001, 296: 756–761.PubMed

17.

Malan TP, Mata HP, Porreca F: Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain. Anesthesiology 2002, 96: 1161–1167. 10.1097/00000542-200205000-00020PubMed

18.

Ugarte SD, Homanics GE, Firestone LL, Hammond DL: Sensory thresholds and the antinociceptive effects of GABA receptor agonists in mice lacking the beta3 subunit of the GABA(A) receptor. Neuroscience 2000, 95: 795–806. 10.1016/S0306-4522(99)00481-9PubMed

19.

Hwang JH, Yaksh TL: The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the rat. Pain 1997, 70: 15–22. 10.1016/S0304-3959(96)03249-6PubMed

20.

Eaton MJ, Plunkett JA, Martinez MA, Lopez T, Karmally S, Cejas P, Whittemore SR: Transplants of neuronal cells bioengineered to synthesize GABA alleviate chronic neuropathic pain. Cell Transplant 1999, 8: 87–101.PubMed

21.

Stubley LA, Martinez MA, Karmally S, Lopez T, Cejas P, Eaton MJ: Only early intervention with gamma-aminobutyric acid cell therapy is able to reverse neuropathic pain after partial nerve injury. J Neurotrauma 2001, 18: 471–477. 10.1089/089771501750171092PubMed

22.

Rode F, Jensen DG, Blackburn-Munro G, Bjerrum OJ: Centrally-mediated antinociceptive actions of GABA(A) receptor agonists in the rat spared nerve injury model of neuropathic pain. Eur J Pharmacol 2005, 516: 131–138. 10.1016/j.ejphar.2005.04.034PubMed

23.

Woolf CJ, Wall PD: Chronic peripheral nerve section diminishes the primary afferent A-fibre mediated inhibition of rat dorsal horn neurones. Brain Res 1982, 242: 77–85. 10.1016/0006-8993(82)90497-8PubMed

24.

Castro-Lopes JM, Tavares I, Coimbra A: GABA decreases in the spinal cord dorsal horn after peripheral neurectomy. Brain Res 1993, 620: 287–291. 10.1016/0006-8993(93)90167-LPubMed

25.

Stiller CO, Cui JG, O'Connor WT, Brodin E, Meyerson BA, Linderoth B: Release of gamma-aminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord stimulation in mononeuropathic rats. Neurosurgery 1996, 39: 367–374. 10.1097/00006123-199608000-00026PubMed

26.

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: 845–858. 10.1016/S0306-4522(96)00341-7PubMed

27.

Ralston DD, Behbehani M, Sehlhorst SC, Meng XW, Ralston HJ: Decreased GABA immunoreactivity in rat dorsal horn is correlated with pain behavior: a light and electron microscope study. Proceedings of the Eighth World Congress on Pain. Edited by: Jensen TS, Turner JA and Wiesenfeld-Hallin Z. Seattle, WA, IASP Press; 1997:547–560.

28.

Eaton MJ, Plunkett JA, Karmally S, Martinez MA, Montanez K: Changes in GAD- and GABA- immunoreactivity in the spinal dorsal horn after peripheral nerve injury and promotion of recovery by lumbar transplant of immortalized serotonergic precursors. J Chem Neuroanat 1998, 16: 57–72. 10.1016/S0891-0618(98)00062-3PubMed

29.

Fukuoka T, Tokunaga A, Kondo E, Miki K, Tachibana T, Noguchi K: Change in mRNAs for neuropeptides and the GABA(A) receptor in dorsal root ganglion neurons in a rat experimental neuropathic pain model. Pain 1998, 78: 13–26. 10.1016/S0304-3959(98)00111-0PubMed

30.

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: 6724–6731.PubMed

31.

Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, De Koninck P, De Koninck Y: Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003, 424: 938–942. 10.1038/nature01868PubMed

32.

Miletic G, Draganic P, Pankratz MT, Miletic V: Muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the GABA transporter GAT-1. Pain 2003, 105: 347–353. 10.1016/S0304-3959(03)00250-1PubMed

33.

Somers DL, Clemente FR: Dorsal horn synaptosomal content of aspartate, glutamate, glycine and GABA are differentially altered following chronic constriction injury to the rat sciatic nerve. Neurosci Lett 2002, 323: 171–174. 10.1016/S0304-3940(02)00157-XPubMed

34.

Polgar E, Hughes DI, Riddell JS, Maxwell DJ, Puskar Z, Todd AJ: Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. Pain 2003, 104: 229–239. 10.1016/S0304-3959(03)00011-3PubMed

35.

Polgar E, Gray S, Riddell JS, Todd AJ: Lack of evidence for significant neuronal loss in laminae I-III of the spinal dorsal horn of the rat in the chronic constriction injury model. Pain 2004, 111: 144–150. 10.1016/j.pain.2004.06.011PubMed

36.

Polgar E, Hughes DI, Arham AZ, Todd AJ: Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain. J Neurosci 2005, 25: 6658–6666. 10.1523/JNEUROSCI.1490-05.2005PubMed

37.

Price TJ, Cervero F, De Koninck Y: Role of cation-chloride-cotransporters (CCC) in pain and hyperalgesia. Curr Top Med Chem 2005, 5: 547–555. 10.2174/1568026054367629PubMedCentralPubMed

38.

Staley KJ, Mody I: Shunting of excitatory input to dentate gyrus granule cells by a depolarizing GABA(A) receptor-mediated postsynaptic conductance. J Neurophysiol 1992, 68: 197–212.PubMed

39.

Gulledge AT, Stuart GJ: Excitatory actions of GABA in the cortex. Neuron 2003, 37: 299–309. 10.1016/S0896-6273(02)01146-7PubMed

40.

Chance FS, Abbott LF, Reyes AD: Gain modulation from background synaptic input. Neuron 2002, 35: 773–782. 10.1016/S0896-6273(02)00820-6PubMed

41.

Prescott SA, De Koninck Y: Gain control of firing rate by shunting inhibition: roles of synaptic noise and dendritic saturation. Proc Natl Acad Sci USA 2003, 100: 2076–2081. 10.1073/pnas.0337591100PubMedCentralPubMed

42.

Coull JAM, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005, 438: 1017–1021. 10.1038/nature04223PubMed

43.

Jensen TS, Baron R: Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003, 102: 1–8. 10.1016/s0304-3959(03)00006-xPubMed

44.

Trevino DL: The origin and projections of a spinal nociceptive and thermoreceptive pathway. In Sensory Functions of the Skin. Edited by: Zotterman Y. Oxford, Pergamon Press; 1976:367–376.

45.

Perl ER: Pain and nociception. In Sensory processes. Edited by: Darian-Smith I. Bethesda, American Physiological Society; 1984:915–975.

46.

Craig AD: Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci 2003, 26: 1–30. 10.1146/annurev.neuro.26.041002.131022PubMed

47.

Craig AD, Kniffki KD: Spinothalamic lumbosacral lamina I cells responsive to skin and muscle stimulation in the cat. J Physiol 1985, 365: 197–221.PubMedCentralPubMed

48.

Bester H, Chapman V, Besson JM, Bernard JF: Physiological properties of the lamina I spinoparabrachial neurons in the rat. J Neurophysiol 2000, 83: 2239–2259.PubMed

49.

Craig AD, Krout K, Andrew D: Quantitative response characteristics of thermoreceptive and nociceptive lamina I spinothalamic neurons in the cat. J Neurophysiol 2001, 86: 1459–1480.PubMed

50.

Andrew D, Craig AD: Responses of spinothalamic lamina I neurons to maintained noxious mechanical stimulation in the cat. J Neurophysiol 2002, 87: 1889–1901.PubMed

51.

Craig AD, Andrew D: Responses of spinothalamic lamina I neurons to repeated brief contact heat stimulation in the cat. J Neurophysiol 2002, 87: 1902–1914.PubMed

52.

Slugg RM, Campbell JN, Meyer RA: The population response of A- and C-fiber nociceptors in monkey encodes high-intensity mechanical stimuli. J Neurosci 2004, 24: 4649–4656. 10.1523/JNEUROSCI.0701-04.2004PubMed

53.

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: 1833–1843. 10.1523/JNEUROSCI.4584-05.2006PubMed

54.

Prescott SA, De Koninck Y: Four cell types with distinctive membrane properties and morphologies in lamina I of the spinal dorsal horn of the adult rat. J Physiol 2002, 539: 817–836. 10.1113/jphysiol.2001.013437PubMedCentralPubMed

55.

Eccles JC: The Physiology of Synapses. Berlin, Springer-Verlag; 1964.

56.

Borg-Graham LJ, Monier C, Fregnac Y: Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 1998, 393: 369–373. 10.1038/30735PubMed

57.

Kontinen VK, Stanfa LC, Basu A, Dickenson AH: Electrophysiologic evidence for increased endogenous GABAergic but not glycinergic inhibitory tone in the rat spinal nerve ligation model of neuropathy. Anesthesiology 2001, 94: 333–339. 10.1097/00000542-200102000-00024PubMed

58.

Chizh BA, Headley PM: NMDA antagonists and neuropathic pain - multiple drug targets and multiple uses. Curr Pharm Des 2005, 11: 2977–2994. 10.2174/1381612054865082PubMed

59.

Isaev D, Gerber G, Park SK, Chung JM, Randik M: Facilitation of NMDA-induced currents and Ca2+ transients in the rat substantia gelatinosa neurons after ligation of L5-L6 spinal nerves. Neuroreport 2000, 11: 4055–4061.PubMed

60.

Kalso E: Sodium channel blockers in neuropathic pain. Curr Pharm Des 2005, 11: 3005–3011. 10.2174/1381612054865028PubMed

61.

Yoshimura M, North RA: Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature 1983, 305: 529–530. 10.1038/305529a0PubMed

62.

Kuhn A, Aertsen A, Rotter S: Neuronal integration of synaptic input in the fluctuation-driven regime. J Neurosci 2004, 24: 2345–2356. 10.1523/JNEUROSCI.3349-03.2004PubMed

63.

Morita K, Tsumoto K, Aihara K: Possible effects of depolarizing GABA(A) conductance on the neuronal input-output relationship: a modeling study. J Neurophysiol 2005, 93: 3504–3523. 10.1152/jn.00988.2004PubMed

64.

Pezet S, McMahon SB: Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci 2006, 29: 507–538. 10.1146/annurev.neuro.29.051605.112929PubMed

65.

Qian N, Sejnowski TJ: When is an inhibitory synapse effective? Proc Natl Acad Sci USA 1990, 87: 8145–8149. 10.1073/pnas.87.20.8145PubMedCentralPubMed

66.

Staley KJ, Soldo BL, Proctor WR: Ionic mechanisms of neuronal excitation by inhibitory GABA(A) receptors. Science 1995, 269: 977–981.PubMed

67.

Staley KJ, Proctor WR: Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cl- and HCO3- transport. J Physiol 1999, 519: 693–712. 10.1111/j.1469-7793.1999.0693n.xPubMedCentralPubMed

68.

Cordero-Erausquin M, Coull JA, Boudreau D, Rolland M, De Koninck Y: Differential maturation of GABA action and anion reversal potential in spinal lamina I neurons: impact of chloride extrusion capacity. J Neurosci 2005, 25: 9613–9623. 10.1523/JNEUROSCI.1488-05.2005PubMed

69.

Kaila K, Lamsa K, Smirnov S, Taira T, Voipio J: Long-lasting GABA-mediated depolarization evoked by high-frequency stimulation in pyramidal neurons of rat hippocampal slice is attributable to a network-driven, bicarbonate-dependent K+ transient. J Neurosci 1997, 17: 7662–7672.PubMed

70.

Jarolimek W, Lewen A, Misgeld U: A furosemide-sensitive K+-Cl- cotransporter counteracts intracellular Cl- accumulation and depletion in cultured rat midbrain neurons. J Neurosci 1999, 19: 4695–4704.PubMed

71.

Todd AJ: GABA and glycine in synaptic glomeruli of the rat spinal dorsal horn. Eur J Neurosci 1996, 8: 2492–2498. 10.1111/j.1460-9568.1996.tb01543.xPubMed

72.

Chéry N, De Koninck Y: Junctional versus extrajunctional glycine and GABA(A) receptor-mediated IPSCs in identified lamina I neurons of the adult rat spinal cord. J Neurosci 1999, 19: 7342–7355.PubMed

73.

Keller AF, Coull JA, Chery N, Poisbeau P, De Koninck Y: Region-specific developmental specialization of GABA-glycine cosynapses in laminas I-II of the rat spinal dorsal horn. J Neurosci 2001, 21: 7871–7880.PubMed

74.

Harvey RJ, Depner UB, Wassle H, Ahmadi S, Heindl C, Reinold H, Smart TG, Harvey K, Schutz B, Abo-Salem OM, Zimmer A, Poisbeau P, Welzl H, Wolfer DP, Betz H, Zeilhofer HU, Muller U: GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science 2004, 304: 884–887. 10.1126/science.1094925PubMed

75.

Zeilhofer HU: The glycinergic control of spinal pain processing. Cell Mol Life Sci 2005, 62: 2027–2035. 10.1007/s00018-005-5107-2PubMed

76.

Poisbeau P, Patte-Mensah C, Keller AF, Barrot M, Breton JD, Luis-Delgado OE, Freund-Mercier MJ, Mensah-Nyagan AG, Schlichter R: Inflammatory pain upregulates spinal inhibition via endogenous neurosteroid production. J Neurosci 2005, 25: 11768–11776. 10.1523/JNEUROSCI.3841-05.2005PubMed

77.

Cummins TR, Dib-Hajj SD, Black JA, Waxman SG: Sodium channels and the molecular pathophysiology of pain. Prog Brain Res 2000, 129: 3–19.PubMed

78.

Julius D, Basbaum AI: Molecular mechanisms of nociception. Nature 2001, 413: 203–210. 10.1038/35093019PubMed

79.

Lewin GR, Lu Y, Park TJ: A plethora of painful molecules. Curr Opin Neurobiol 2004, 14: 443–449. 10.1016/j.conb.2004.07.009PubMed

80.

Melzack R, Wall PD: Pain mechanisms: a new theory. Science 1965, 150: 971–979. 10.1126/science.150.3699.971PubMed

81.

Game CJ, Lodge D: The pharmacology of the inhibition of dorsal horn neurones by impulses in myelinated cutaneous afferents in the cat. Exp Brain Res 1975, 23: 75–84. 10.1007/BF00238730PubMed

82.

Baba H, Ji RR, Kohno T, Moore KA, Ataka T, Wakai A, Okamoto M, Woolf CJ: Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn. Mol Cell Neurosci 2003, 24: 818–830. 10.1016/S1044-7431(03)00236-7PubMed

83.

Furue H, Katafuchi T, Yoshimura M: Sensory processing and functional reorganization of sensory transmission under pathological conditions in the spinal dorsal horn. Neurosci Res 2004, 48: 361–368. 10.1016/j.neures.2003.12.005PubMed

84.

Seagrove LC, Suzuki R, Dickenson AH: Electrophysiological characterisations of rat lamina I dorsal horn neurones and the involvement of excitatory amino acid receptors. Pain 2004, 108: 76–87. 10.1016/j.pain.2003.12.004PubMed

85.

Buesa I, Ortiz V, Aguilera L, Torre F, Zimmermann M, Azkue JJ: Disinhibition of spinal responses to primary afferent input by antagonism at GABA receptors in urethane-anaesthetised rats is dependent on NMDA and metabotropic glutamate receptors. Neuropharmacology 2006.

86.

McGowan MK, Hammond DL: Intrathecal GABA(B) antagonists attenuate the antinociception produced by microinjection of L-glutamate into the ventromedial medulla of the rat. Brain Res 1993, 607: 39–46. 10.1016/0006-8993(93)91487-DPubMed

87.

Antal M, Petko M, Polgar E, Heizmann CW, Storm-Mathisen J: Direct evidence of an extensive GABAergic innervation of the spinal dorsal horn by fibres descending from the rostral ventromedial medulla. Neuroscience 1996, 73: 509–518. 10.1016/0306-4522(96)00063-2PubMed

88.

Lin Q, Peng YB, Willis WD: Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is reduced during central sensitization. J Neurophysiol 1996, 76: 1005–1014.PubMed

89.

Peng YB, Lin Q, Willis WD: Effects of GABA and glycine receptor antagonists on the activity and PAG-induced inhibition of rat dorsal horn neurons. Brain Res 1996, 736: 189–201. 10.1016/0006-8993(96)00668-3PubMed

90.

Hao JX, Xu XJ, Aldskogius H, Seiger A, Wiesenfeld-Hallin Z: Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation. Pain 1991, 45: 175–185. 10.1016/0304-3959(91)90186-2PubMed

91.

Xu XJ, Hao JX, Aldskogius H, Seiger A, Wiesenfeld-Hallin Z: Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury. Pain 1992, 48: 279–290. 10.1016/0304-3959(92)90070-RPubMed

92.

Woolf CJ, Bennett GJ, Doherty M, Dubner R, Kidd B, Koltzenburg M, Lipton R, Loeser JD, Payne R, Torebjork E: Towards a mechanism-based classification of pain? Pain 1998, 77: 227–229. 10.1016/S0304-3959(98)00099-2PubMed

93.

Block BM, Hurley RW, Raja SN: Mechanism-based therapies for pain. Drug News Perspect 2004, 17: 172–186. 10.1358/dnp.2004.17.3.829015PubMed

94.

Smith PA: Neuropathic pain: drug targets for current and future interventions. Drug News Perspect 2004, 17: 5–17. 10.1358/dnp.2004.17.1.829021PubMed

95.

Woolf CJ: Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004, 140: 441–451.PubMed

96.

Harden RN: Chronic neuropathic pain. Mechanisms, diagnosis, and treatment. Neurologist 2005, 11: 111–122. 10.1097/01.nrl.0000155180.60057.8ePubMed

97.

Hines ML, Carnevale NT: The NEURON simulation environment. Neural Comput 1997, 9: 1179–1209. 10.1162/neco.1997.9.6.1179PubMed

98.

Mainen ZF, Joerges J, Huguenard JR, Sejnowski TJ: A model of spike initiation in neocortical pyramidal neurons. Neuron 1995, 15: 1427–1439. 10.1016/0896-6273(95)90020-9PubMed

99.

Traub RD, Miles R: Neuronal Networks of the Hippocampus. Cambridge,U.K., Cambridge; 1991.

100.

Prescott SA, De Koninck Y: Integration time in a subset of spinal lamina I neurons is lengthened by sodium and calcium currents acting synergistically to prolong subthreshold depolarization. J Neurosci 2005, 25: 4743–4754. 10.1523/JNEUROSCI.0356-05.2005PubMed

101.

Mainen ZF, Sejnowski TJ: Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 1996, 382: 363–366. 10.1038/382363a0PubMed

102.

Dahlhaus A, Ruscheweyh R, Sandkuhler J: Synaptic input of rat spinal lamina I projection and unidentified neurones in vitro. J Physiol 2005, 566: 355–368. 10.1113/jphysiol.2005.088567PubMedCentralPubMed

103.

Jahr CE, Stevens CF: A quantitative description of NMDA receptor-channel kinetic behavior. J Neurosci 1990, 10: 1830–1837.PubMed

104.

Jahr CE, Stevens CF: Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics. J Neurosci 1990, 10: 3178–3182.PubMed

105.

Destexhe A, Mainen ZF, Sejnowski TJ: Kinetic models of synaptic transmission. In Methods in Neuronal Modeling. Volume 1. 2nd edition. Edited by: Koch C and Segev I. Cambridge, MA, MIT; 1998:1–25.

106.

Furue H, Narikawa K, Kumamoto E, Yoshimura M: Responsiveness of rat substantia gelatinosa neurones to mechanical but not thermal stimuli revealed by in vivo patch-clamp recording. J Physiol 1999, 521 Pt 2: 529–535. 10.1111/j.1469-7793.1999.00529.xPubMed

Title: Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain
Authors: Steven A Prescott
Terrence J Sejnowski
Yves De Koninck
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2006
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-2-32

2024 ASCO Annual Meeting

Springer Medicine

Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain

Abstract

Background

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Results

Conclusion

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