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Experimental Brain Research

Erschienen in:

01.06.2009 | Review

Ectopic discharge in Aβ afferents as a source of neuropathic pain

verfasst von: Marshall Devor

Erschienen in: Experimental Brain Research | Ausgabe 1/2009

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Abstract

Ectopic discharge in axotomized dorsal root ganglion neurons is a key driver of neuropathic pain. However, the bulk of this activity is generated and carried centrally in large diameter myelinated Aβ afferents, a cell type that normally signals touch and vibration sense. Evidence is considered suggesting that following axotomy, Aβ afferents undergo a change in their electrical characteristics and also in the neurotransmitter complement that they express. This dual phenotypic switching renders them capable of (1) directly driving postsynaptic pain signaling pathways in the spinal cord, and (2) triggering and maintaining central sensitization.

Abdulla FA, Smith PA (2001) Changes in Na⁺ channel currents of rat dorsal root ganglion neurons following axotomy and axotomy-induced autotomy. J Neurophysiol 88:2518–2529CrossRef

Alano CC, Kauppinen TM, Valls AV, Swanson RA (2006) Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci USA 103:9685–9690PubMedCrossRef

Allen BJ, Li J, Menning PM, Rogers SD, Ghilardi J, Mantyh PW, Simone DA (1999) Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury. J Neurophysiol 81:1379–1390PubMed

Amir R, Michaelis M, Devor M (1999) Membrane potential oscillations in dorsal root ganglion neurons: role in normal electrogenesis and in neuropathic pain. J Neurosci 19:8589–8596PubMed

Amir R, Liu CN, Kocsis JD, Devor M (2002) Oscillatory mechanism in primary sensory neurones. Brain 125:421–435PubMedCrossRef

Amir R, Kocsis JD, Devor M (2005) Multiple interacting sites of ectopic spike electrogenesis in primary sensory neurons. J Neurosci 25:2576–2585PubMedCrossRef

Amir R, Argoff CE, Bennett GJ, Cummins TR, Durieux ME, Gerner P, Gold MS, Porreca F, Strichartz GR (2006) The role of sodium channels in chronic inflammatory and neuropathic pain. J Pain 7:S1–S29PubMedCrossRef

Andrew D, Greenspan JD (1999) Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat. J Neurophysiol 82:2649–2656PubMed

Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB, Gitelman DR (2004) Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci 24:10410–10415PubMedCrossRef

Banik RK, Brennan TJ (2004) Spontaneous discharge and increased heat sensitivity of rat C-fiber nociceptors are present in vitro after plantar incision. Pain 112:204–213PubMedCrossRef

Banik RK, Brennan TJ (2008) Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation. Pain 138(2):380–391PubMedCrossRef

Bao L, Wang HF, Cai HJ, Tong YG, Jin SX, Lu YJ, Grant G, Hokfelt T, Zhang X (2002) Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord. Eur J Neurosci 16:175–185PubMedCrossRef

Baron R, Saguer M (1993) Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 116(Pt 6):1477–1496PubMedCrossRef

Battaglia AA, Sehayek K, Grist J, McMahon SB, Gavazzi I (2003) EphB receptors and ephrin-B ligands regulate spinal sensory connectivity and modulate pain processing. Nat Neurosci 6:339–340PubMedCrossRef

Ben-Chaim Y, Chanda B, Dascal N, Bezanilla F, Parnas I, Parnas H (2006) Movement of ‘gating charge’ is coupled to ligand binding in a G-protein-coupled receptor. Nature 444:106–109PubMedCrossRef

Birbaumer N, Lutzenberger W, Montoya P, Larbig W, Unertl K, Topfner S, Grodd W, Taub E, Flor H (1997) Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization. J Neurosci 17:5503–5508PubMed

Blenk K, Habler H, Janig W (1997) Neomycin and gadolinium applied to an L5 spinal nerve lesion prevent mechanical allodynia-like behaviour in rats. Pain 70:155–165PubMedCrossRef

Boada MD, Woodbury CJ (2008) Myelinated skin sensory neurons project extensively throughout adult mouse substantia gelatinosa. J Neurosci 28:2006–2014PubMedCrossRef

Boucher TJ, McMahon SB (2001) Neurotrophic factors and neuropathic pain. Curr Opin Pharmacol 1:66–72PubMedCrossRef

Campbell AW (1905) Histological studies on the localization of cerebral function. Cambridge University Press, Cambridge

Campbell JN, Raja SN, Meyer RA, MacKinnon SE (1988) Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain 32:89–94PubMedCrossRef

Cao X, Xie H, Yang R, Lei G, Li F, Li A, Liu C, Liu L (2007) Effects of capsaicin on VGSCs in TRPV1-/- mice. Brain Res 1163:33–43PubMedCrossRef

Castro-Lopes JM, Tavares I, Coimbra A (1993) GABA decreases in the spinal cord dorsal horn after peripheral neurectomy. Brain Res 620:287–291PubMedCrossRef

Chen Y, Devor M (1998) Ectopic mechanosensitivity in injured sensory axons arises from the site of spontaneous electrogenesis. Eur J Pain 2:165–178PubMedCrossRef

Costigan M, Befort K, Karchewski L, Griffin RS, D’Urso D, Allchorne A, Sitarski J, Mannion JW, Pratt RE, Woolf CJ (2002) Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 3:16–28PubMedCrossRef

Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444:894–898PubMedCrossRef

Craig AD (2003) Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci 26:1–30PubMedCrossRef

Cummins TR, Dib-Hajj SD, Waxman SG (2004) Electrophysiological properties of mutant Nav 1.7 sodium channels in a painful inherited neuropathy. J Neurosci 24:8232–8236PubMedCrossRef

Dalal A, Tata M, Allegre G, Gekiere F, Bons N, Albe-Fessard D (1999) Spontaneous activity of rat dorsal horn cells in spinal segments of sciatic projection following transection of sciatic nerve or of corresponding dorsal roots. Neuroscience 94:217–228PubMedCrossRef

Decosterd I, Allchorne A, Woolf CJ (2002) Progressive tactile hypersensitivity after a peripheral nerve crush: non-noxious mechanical stimulus-induced neuropathic pain. Pain 100:155–162PubMedCrossRef

Devor M (1999) Unexplained peculiarities of the dorsal root ganglion. Pain suppl 6:S27–S35PubMedCrossRef

Devor M (2006a) Centralization, central sensitization and neuropathic pain. Focus on “sciatic chronic constriction injury produces cell-type-specific changes in the electrophysiological properties of rat substantia gelatinosa neurons”. J Neurophysiol 96:522–523PubMedCrossRef

Devor M (2006b) Pain cortex, and consciousness. Behav Brain Sci 30:89–90

Devor M (2006c) Peripheral nerve generators of neuropathic pain. In: Campbell JN, Basbaum AI, Dray A, Dubner R, Dworkin RH, Sang CN (eds) Emerging strategies for the treatment of neuropathic pain. IASP Press, Seattle, pp 37–68

Devor M (2006d) Response of nerves to injury in relation to neuropathic pain. In: McMahon SL, Koltzenburg M (eds) Wall and Melzack’s textbook of pain, 5th edn. Churchill Livingstone, London, pp 905–927

Devor M (2007) Central changes after nerve injury. In: Willis W, Schmidt R (eds) Encyclopedia of pain. Springer, Berlin

Devor M, Govrin-Lippmann R, Raber P (1985) Corticosteroids suppress ectopic neuronal discharge originating in experimental neuromas. Pain 22:127–137PubMedCrossRef

Devor M, Keller CH, Deerinck TJ, Levinson SR, Ellisman M (1989) Na⁺ channel accumulation on axolemma of afferent endings in nerve-end neuromas in Apteronotus. Neurosci Lett 102:149–154PubMedCrossRef

Devor M, Govrin-Lippmann R, Angelides K (1993) Na⁺ channel immuno-localization in peripheral mammalian axons and changes following nerve injury and neuroma formation. J Neurosci 13:1976–1992PubMed

Djouhri L, Lawson SN (2004) Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals. Brain Res Brain Res Rev 46:131–145PubMedCrossRef

Duggan AW, Hope PJ, Jarrott B, Schaible HG, Fleetwood-Walker SM (1990) Release, spread and persistence of immunoreactive neurokinin A in the dorsal horn of the cat following cutaneous stimulation. Studies with antibody microprobes. Neuroscience 35:195–202PubMedCrossRef

England JD, Happel LT, Kline DG, Gamboni F, Thouron CL, Liu ZP, Levinson SR (1996) Sodium channel accumulation in humans with painful neuromas. Neurology 47:272–276PubMed

Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, Ostman J, Klugbauer N, Wood JN, Gardiner RM, Rees M (2006) SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 52:767–774PubMedCrossRef

Fields RD (1996) Signaling from neural impulses to genes. Neuroscientist 2:315–325

Fields RD, Eshete F, Dudek S, Ozsarac N, Stevens B (2001) Regulation of gene expression by action potentials: dependence on complexity in cellular information processing. Novartis Found Symp 239:160–172PubMedCrossRef

Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, Larbig W, Taub E (1995) Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375:482–484PubMedCrossRef

Fried K, Govrin-Lippmann R, Rosenthal F, Ellisman M, Devor M (1991) Ultra-structure of afferent axon endings in a neuroma. J Neurocytol 20:682–701PubMedCrossRef

Gold MS, Reichling DB, Shuster MJ, Levine JD (1996) Hyperalgesic agents increase a tetrodotoxin-resistant Na⁺ current in nociceptors. Proc Natl Acad Sci USA 93:1108–1112PubMedCrossRef

Gonzalez JC, Egea J, Del Carmen Godino M, Fernandez-Gomez FJ, Sanchez-Prieto J, Gandia L, Garcia AG, Jordan J, Hernandez-Guijo JM (2007) Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca(2+) signalling in hippocampal neurons. Eur J Neurosci 26:2481–2495PubMedCrossRef

Gracely R, Lynch S, Bennett G (1992) Painful neuropathy: altered central processing, maintained dynamically by peripheral input. Pain 51:175–194PubMedCrossRef

Gu X, Wang S, Yang L, Sung B, Lim G, Mao J, Zeng Q, Chang Y (2007) Time-dependent effect of epidural steroid on pain behavior induced by chronic compression of dorsal root ganglion in rats. Brain Res 1174:39–46PubMedCrossRef

Haeseler G, Tetzlaff D, Bufler J, Dengler R, Munte S, Hecker H, Leuwer M (2003) Blockade of voltage-operated neuronal and skeletal muscle sodium channels by S(+)- and R(−)-ketamine. Anesth Analg 96:1019–1026PubMedCrossRef

Han H, Lee D, Chung J (2000) Characteristics of ectopic discharges in a rat neuropathic pain model. Pain 84:253–261PubMedCrossRef

Harris AJ (1999) Cortical origin of pathological pain. Lancet 354:1464–1466PubMedCrossRef

Harty TP, Dib-Hajj SD, Tyrrell L, Blackman R, Hisama FM, Rose JB, Waxman SG (2006) Nav 1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive dorsal root ganglion neurons. J Neurosci 26:12566–12575PubMedCrossRef

Hoffmann T, Sauer SK, Horch RE, Reeh PW (2008) Sensory transduction in peripheral nerve axons elicits ectopic action potentials. J Neurosci 28(RC140):6281–6284PubMedCrossRef

Hughes DI, Scott DT, Riddell JS, Todd AJ (2007) Upregulation of substance P in low-threshold myelinated afferents is not required for tactile allodynia in the chronic constriction injury and spinal nerve ligation models. J Neurosci 27:2035–2044PubMedCrossRef

Ibuki T, Hama AT, Wang XT, Pappas GD, Sagen J (1997) Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts. Neuroscience 76:845–858PubMedCrossRef

Kaczmarek LK (2006) Non-conducting functions of voltage-gated ion channels. Nat Rev Neurosci 7:761–771PubMedCrossRef

Kalso E (1997) Prevention of chronicity. In: Jensen TS, Turner JA, Wiesenfeld-Hallin ZH (eds) Proceedings of the 8th world congress on pain. Progress in pain research and management, vol 8. IASP Press, Seattle, pp 215–230

Kapoor R, Li Y-G, Smith K (1997) Slow sodium-dependent potential oscillations contribute to ectopic firing in mammalian demyelinated axons. Brain 120:647–652PubMedCrossRef

Khan GM, Chen SR, Pan HL (2002) Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats. Neuroscience 114:291–299PubMedCrossRef

Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:355–363PubMedCrossRef

Kim HK, Schattschneider J, Lee I, Chung K, Baron R, Chung JM (2007) Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli. Pain 129:93–101PubMedCrossRef

Kinnman E, Levine J (1995) Sensory and sympathetic contributions to nerve injury-induced sensory abnormalities in the rat. Neuroscience 64:751–767PubMedCrossRef

Klein JP, Tendi EA, Dib-Hajj SD, Fields RD, Waxman SG (2003) Patterned electrical activity modulates sodium channel expression in sensory neurons. J Neurosci Res 74:192–198PubMedCrossRef

Kocsis JD, Devor M (2000) Altered excitability of large diameter cutaneous afferents following nerve injury: consequences for chronic pain. In: Devor M, Rowbotham MC, Wiesenfeld-Hallin Z (eds), Proceedings of the 9th world congress on pain, progress in pain research and management, vol 16, IASP Press, Seattle

Koltzenburg M, Kees S, Budweiser S, Ochs G, Toyka KV (1994a) The properties of unmyelinated nociceptive afferents change in a painful chronic constriction neuropathy. In: Gebhart G, Hammond D, Jensen T (eds) Progress in pain research and management, vol 2. IASP Press, Seattle, pp 511–521

Koltzenburg M, Torebjork H, Wahren L (1994b) Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain. Brain 117:579–591PubMedCrossRef

Kovalsky Y, Amir R, Devor M (2008) Subthreshold oscillations facilitate neuropathic spike discharge by overcoming membrane accommodation. Exp Neurol 210:194–206PubMedCrossRef

Lawson SN (2002) Phenotype and function of somatic primary afferent nociceptive neurones with C-Adelta- or Aalpha/beta-fibres. Exp Physiol 87:239–244PubMedCrossRef

Lever IJ, Bradbury EJ, Cunningham JR, Adelson DW, Jones MG, McMahon SB, Marvizon JC, Malcangio M (2001) Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. J Neurosci 21:4469–4477PubMed

Li M, West JW, Lai Y, Scheuer Y, Catterall WA (1992) Functional modulation of brain sodium channels by cAMP-dependent phosphorylation. Neuron 8:1151–1159PubMedCrossRef

Li Y, Dorsi MJ, Meyer RA, Belzberg AJ (2000) Mechanical hyperalgesia after an L5 spinal nerve lesion in the rat is not dependent on input from injured nerve fibers. Pain 85:493–502PubMedCrossRef

Lindblom U, Verrillo RT (1979) Sensory functions in chronic neuralgia. J Neurol Neurosurg Psychiatry 42:422–435PubMedCrossRef

Liu C-N, Michaelis M, Amir R, Devor M (2000a) Spinal nerve injury enhances subthreshold membrane potential oscillations in DRG neurons: relation to neuropathic pain. J Neurophysiol 84:205–215PubMed

Liu C-N, Wall PD, Ben-Dor E, Michaelis M, Amir R, Devor M (2000b) Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury. Pain 85:503–521PubMedCrossRef

Liu X, Eschenfelder S, Blenk K-H, Janig W, Habler H-J (2000c) Spontaneous activity of axotomized afferent neurons after L5 spinal nerve injury in rats. Pain 84:309–318PubMedCrossRef

Liu L, Oortgiesen M, Li L, Simon SA (2001a) Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons. J Neurophysiol 85:745–758PubMed

Liu CN, Raber P, Ziv-Sefer S, Devor M (2001b) Hyperexcitability in sensory neurons of rats selected for high versus low neuropathic pain phenotype. Neuroscience 105:265–275PubMedCrossRef

Ma W, Ramer MS, Bisby MA (1999) Increased calcitonin gene-related peptide immunoreactivity in gracile nucleus after partial sciatic nerve injury: age-dependent and originating from spared sensory neurons. Exp Neurol 159:459–473PubMedCrossRef

Malcangio M, Ramer MS, Jones MG, McMahon SB (2000) Abnormal substance P release from the spinal cord following injury to primary sensory neurons. Eur J Neurosci 12:397–399PubMedCrossRef

Marchand JE, Wurm WH, Kato T, Kream RM (1994) Altered tachykinin expression by dorsal root ganglion neurons in a rat model of neuropathic pain. Pain 58:219–231PubMedCrossRef

Matsumoto M, Inoue M, Hald A, Xie W, Ueda H (2006) Inhibition of paclitaxel-induced A-fiber hypersensitization by gabapentin. J Pharmacol Exp Ther 318:735–740PubMedCrossRef

Matzner O, Devor M (1994) Hyperexcitability at sites of nerve injury depends on voltage -sensitive Na+ channels. J Neurophysiol 72:349–357PubMed

Meiri H, Spira ME, Parnas I (1981) Membrane conductance and action potential of a regenerating axonal tip. Science 211:709–712PubMedCrossRef

Melzack R (1989) Phantom limbs the self and the brain. Can Psychol 30:1–16CrossRef

Michael GJ, Averill S, Shortland PJ, Yan Q, Priestley JV (1999) Axotomy results in major changes in BDNF expression by dorsal root ganglion cells: BDNF expression in large trkB and trkC cells in pericellular baskets, and in projections to deep dorsal horn and dorsal column nuclei. Eur J Neurosci 11:3539–3551PubMedCrossRef

Michaelis M, Blenk K-H, Janig W, Vogel C (1995) Development of spontaneous activity and mechano-sensitivity in axotomized afferent nerve fibers during the first hours after nerve transection in rats. J Neurophysiol 74:1020–1027PubMed

Miki K, Fukuoka T, Tokunaga A, Noguchi K (1998) Calcitonin gene-related peptide increase in the rat spinal dorsal horn and dorsal column nucleus following peripheral nerve injury: up-regulation in a subpopulation of primary afferent sensory neurons. Neuroscience 82:1243–1252PubMedCrossRef

Molander C, Hongpaisan J, Persson JK (1994) Distribution of c-fos expressing dorsal horn neurons after electrical stimulation of low threshold sensory fibers in the chronically injured sciatic nerve. Brain Res 644:74–82PubMedCrossRef

Nagy JI, Buss M, Mallory B (1986) Autotomy in rats after peripheral nerve section: lack of effect of topical nerve or neonatal capsaicin treatment. Pain 24:75–86PubMedCrossRef

Nassar MA, Baker MD, Levato A, Ingram R, Mallucci G, McMahon SB, Wood JN (2006) Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice. Mol Pain 2:33PubMedCrossRef

Neumann S, Doubell TP, Leslie TA, Woolf CJ (1996) Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 384:360–364PubMedCrossRef

Neumann S, Braz JM, Skinner K, Llewellyn-Smith IJ, Basbaum AI (2008) Innocuous not noxious, input activates PKCgamma interneurons of the spinal dorsal horn via myelinated afferent fibers. J Neurosci 28:7936–7944PubMedCrossRef

Noguchi K, Kawai Y, Fukuoka T, Senba E, Miki K (1995) Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons. J Neurosci 15:7633–7643PubMed

Nordin M, Nystrom B, Wallin U, Hagbarth K-E (1984) Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves dorsal roots and dorsal columns. Pain 20:231–245PubMedCrossRef

Obata K, Yamanaka H, Dai Y, Mizushima T, Fukuoka T, Tokunaga A, Noguchi K (2004) Differential activation of MAPK in injured and uninjured DRG neurons following chronic constriction injury of the sciatic nerve in rats. Eur J Neurosci 20:2881–2895PubMedCrossRef

Ossipov M, Bian D, Malan TJ, Lai J, Porreca F (1999) Lack of involvement of capsaicin-sensitive primary afferents in nerve-ligation injury induced tactile allodynia in rats. Pain 79:127–133PubMedCrossRef

Pan HL, Eisenach JC, Chen SR (1999) Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats. J Pharmacol Exp Ther 288:1026–1030PubMed

Persson A-K, Gebauer M, Jordan S, Metz-Weidmann C, Schulte AM, Schneider H-C, Ding-Pfennigdorff D, Thun J, Xu X-J, Wiesenfeld-Hallin Z, Darvasi A, Fried K, Devor M (2009) Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain. Mol Pain (in press)

Pfeffer SR (2007) Unsolved mysteries in membrane traffic. Annu Rev Biochem 76:629–645PubMedCrossRef

Pitcher GM, Henry JL (2004) Nociceptive response to innocuous mechanical stimulation is mediated via myelinated afferents and NK-1 receptor activation in a rat model of neuropathic pain. Exp Neurol 186:173–197PubMedCrossRef

Pitcher GM, Henry JL (2008) Governing role of primary afferent drive in increased excitation of spinal nociceptive neurons in a model of sciatic neuropathy. Exp Neurol 214:219–228PubMedCrossRef

Puil E, Gimbarzevsky B, Spigelman I (1988) Primary involvement of K⁺ conductance in membrane resonance of trigeminal root ganglion neurons. J Neurophysiol 59:77–89PubMed

Reeh PW, Bayer J, Kocher L, Handwerker HO (1987) Sensitization of nociceptive cutaneous nerve fibers from the rat’s tail by noxious mechanical stimulation. Exp Brain Res 65:505–512PubMedCrossRef

Rizzo M, Kocsis J, Waxman S (1996) Mechanism of paraesthesiae and hyperaesthesiae: role of Na⁺ channel heterogeneity. Eur Neurol 36:3–12PubMedCrossRef

Saade NE, Baliki M, El-Khoury C, Hawwa N, Atweh SF, Apkarian AV, Jabbur SJ (2002) The role of the dorsal columns in neuropathic behavior: evidence for plasticity and non-specificity. Neuroscience 115:403–413PubMedCrossRef

Schaible HG, Hope PJ, Lang CW, Duggan AW (1992) Calcitonin gene-related peptide causes intraspinal spreading of substance P released by peripheral stimulation. Eur J Neurosci 4:750–757PubMedCrossRef

Schmidt R, Schmelz M, Forster C, Ringkamp M, Torebjork E, Handwerker H (1995) Novel classes of responsive and unresponsive C nociceptors in human skin. J Neurosci 15:333–341PubMed

Schoffnegger D, Ruscheweyh R, Sandkuhler J (2008) Spread of excitation across modality borders in spinal dorsal horn of neuropathic rats. Pain 135:300–310PubMedCrossRef

Sheen K, Chung JM (1993) Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model. Brain Res 610:62–68PubMedCrossRef

Shehab SA, Spike RC, Todd AJ (2004) Do central terminals of intact myelinated primary afferents sprout into the superficial dorsal horn of rat spinal cord after injury to a neighboring peripheral nerve? J Comp Neurol 474:427–437PubMedCrossRef

Sherrington CS (1906) The integrative action of the nervous system. Constable, London

Shim B, Kim DW, Kim BH, Nam TS, Leem JW, Chung JM (2005) Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropathy. Neuroscience 132:193–201PubMedCrossRef

Shir Y, Seltzer Z (1990) A-fibers mediate mechanical hyperesthesia and allodynia and C-fibers mediate thermal hyperalgesia in a new model of causalgiform pain disorders in rats. Neurosci Lett 115:62–67PubMedCrossRef

Sotgiu ML, Biella G, Riva L (1994) A study of early ongoing activity in dorsal horn units following sciatic nerve constriction. NeuroReport 5:2609–2612PubMed

Sukhotinsky I, Ben-Dor E, Raber P, Devor M (2004) Key role of the dorsal root ganglion in neuropathic tactile hypersensibility. Eur J Pain 8:135–143PubMedCrossRef

Sun H, Ren K, Zhong CM, Ossipov MH, Malan TP, Lai J, Porreca F (2001) Nerve injury-induced tactile allodynia is mediated via ascending spinal dorsal column projections. Pain 90:105–111PubMedCrossRef

Sun Q, Tu H, Xing GG, Han JS, Wan Y (2005) Ectopic discharges from injured nerve fibers are highly correlated with tactile allodynia only in early but not late, stage in rats with spinal nerve ligation. Exp Neurol 191:128–136PubMedCrossRef

Tal M, Kim J, Back SK, Na HS, Devor M (2006) Onset of ectopic firing in the Chung model of neuropathic pain coincides with the onset of tactile allodynia. In: Flor H, Kalso E, Dostrovsky JO (eds), Proceedings of the 11th world congress on pain, IASP Press, Seattle, pp 119–130

Tessler MJ, Kleiman SJ (1994) Spinal anaesthesia for patients with previous lower limb amputations. Anaesthesia 49:439–441PubMedCrossRef

Torebjork H, Lundberg L, LaMotte R (1992) Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol 448:765–780PubMed

Tracey I, Mantyh PW (2007) The cerebral signature for pain perception and its modulation. Neuron 55:377–391PubMedCrossRef

Tsuboi Y, Takeda M, Tanimoto T, Ikeda M, Matsumoto S, Kitagawa J, Teramoto K, Simizu K, Yamazaki Y, Shima A, Ren K, Iwata K (2004) Alteration of the second branch of the trigeminal nerve activity following inferior alveolar nerve transection in rats. Pain 111:323–334PubMedCrossRef

Vallbo AB, Hagbarth KE, Torebjork HE, Wallin BG (1979) Somatosensory proprioceptive, and sympathetic activity in human peripheral nerves. Physiol Rev 59:919–957PubMed

Wagner LE 2nd, Gingrich KJ, Kulli JC, Yang J (2001) Ketamine blockade of voltage-gated sodium channels: evidence for a shared receptor site with local anesthetics. Anesthesiology 95:1406–1413PubMedCrossRef

Wang GK, Russell C, Wang SY (2004) State-dependent block of voltage-gated Na⁺ channels by amitriptyline via the local anesthetic receptor and its implication for neuropathic pain. Pain 110:166–174PubMedCrossRef

Watkins LR, Maier SF (2002) Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 82:981–1011PubMed

Waxman SG (ed) (2002) Sodium channels and neuronal hyperexcitability, Novartis Found Symp, vol 241, Wiley, West Sussex, UK, 232 p

Waxman SG, Dib-Hajj S (2005) Erythermalgia: molecular basis for an inherited pain syndrome. Trends Mol Med 11:555–562PubMedCrossRef

Waxman SG, Kocsis JD, Black JA (1994) Type III sodium channel mRNA is expressed in embryonic but not in adult spinal sensory neurons, and is re-expressed following axotomy. J Neurophysiol 72:466–470PubMed

Weissner W, Winterson BJ, Stuart-Tilley A, Devor M, Bove GM (2006) Time course of substance P expression in dorsal root ganglia following complete spinal nerve transection. J Comp Neurol 497:78–87PubMedCrossRef

Willis W (1992) Hyperalgesia and allodynia. Raven Press, New York, pp 173–385, 400

Woolf CJ, Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288:1765–1769PubMedCrossRef

Woolf C, Thompson S (1991) The induction and maintenance of central sensitization is dependent on N-methyl d-aspartic acid receptor activation: implications for the treatment of post injury pain hypersensitivity states. Pain 44:293–299PubMedCrossRef

Wu G, Ringkamp M, Hartke TV, Murinson BB, Campbell JN, Griffin JW, Meyer RA (2001a) Early onset of spontaneous activity in uninjured C-fiber nociceptors after injury to neighboring nerve fibers. J Neurosci 21(8):RC140PubMed

Wu N, Hsiao C-F, Chandler S (2001b) Membrane resonance and subthreshold membrane oscillations in mesencephalic V neurons: participants in burst generation. J Neurosci 21:3729–3739PubMed

Xiao HS, Huang QH, Zhang FX, Bao L, Lu YJ, Guo C, Yang L, Huang WJ, Fu G, Xu SH, Cheng XP, Yan Q, Zhu ZD, Zhang X, Chen Z, Han ZG, Zhang X (2002) Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci USA 99:8360–8365PubMedCrossRef

Xie W, Strong JA, Meij JT, Zhang JM, Yu L (2005) Neuropathic pain: early spontaneous afferent activity is the trigger. Pain 116:243–256PubMedCrossRef

Yang RH, Xing JL, Duan JH, Hu SJ (2005) Effects of gabapentin on spontaneous discharges and subthreshold membrane potential oscillation of type A neurons in injured DRG. Pain 116:187–193PubMedCrossRef

Zheng JH, Song XJ (2005) Abeta-afferents activate neurokinin-1 receptor in dorsal horn neurons after nerve injury. Neuroreport 16:715–719PubMedCrossRef

Zhou ZS, Zhao ZQ (2000) Ketamine blockage of both tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels of rat dorsal root ganglion neurons. Brain Res Bull 52:427–433PubMedCrossRef

Ziegler EA, Magerl W, Meyer RA, Treede RD (1999) Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. Brain 122:2245–2257PubMedCrossRef

Titel: Ectopic discharge in Aβ afferents as a source of neuropathic pain
verfasst von: Marshall Devor
Publikationsdatum: 01.06.2009
Verlag: Springer-Verlag
Erschienen in: Experimental Brain Research / Ausgabe 1/2009
Print ISSN: 0014-4819
Elektronische ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-009-1724-6

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Ectopic discharge in Aβ afferents as a source of neuropathic pain

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