Skip to main content
SpringerLink
Log in
Book cover

Toll-like Receptors: Roles in Infection and Neuropathology pp 169–186Cite as

Toll-Like Receptors in Peripheral Nerve Injury and Neuropathic Pain

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 336))

Abstract

Peripheral nerve injury triggers a series of responses in the injured nerve, such as the dissolution of distal axons, the activation of Schwann cells, the production of various proinflammatory mediators, and the infiltration of circulating immune cells. These orchestrated events regulate the degeneration and subsequent regeneration of the injured nerve. In addition, peripheral nerve injury often accompanies chronic pain. Studies in this field have revealed that spinal cord microglia activation plays a critical role in the development of pain hypersensitivity. Recent studies using genetically modified mice indicate that Toll-like receptors (TLRs) are involved in nerve degeneration (Wallerian degeneration) and chronic pain (neuropathic pain) development after nerve injury. Here, we review studies that have implicated TLRs in mediating nerve degeneration/regeneration and neuropathic pain following nerve injury. In addition, we discuss possible mechanisms underlying the roles of TLRs in these neurological disorders.

D. Kim and S. Lee contributed equally in writing this chapter

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ATP:

Adenosine triphosphate

BDNF:

Brain-derived neurotrophic factor

CNTF:

Ciliary neurotrophic factor

COX-2:

Cyclooxygenase 2

DRG:

Dorsal root ganglia

FGF:

Fibroblast growth factor

GDNF:

Glial cell line-derived neurotrophic factor

HMGB1:

High mobility group box 1 protein

HSP:

Heat-shock protein

iNOS:

Inducible nitric oxide synthase

LIF:

Leukemia inhibitory factor

LPA:

Lysophosphatidic acid

MCP-1:

Monocyte chemoattractant protein 1 (CCL2)

MIP-1α:

Macrophage inflammatory protein 1α (CCL3)

NGF:

Nerve growth factor

NO:

Nitric oxide

Poly I:C:

Polyinosinic:polycytidylic acid

PNS:

Peripheral nervous system

RANTES:

Regulated upon activation, normal T cell expressed and secreted (CCL5)

TLR:

Toll-like receptor

References

  • Applequist SE, Wallin RP, Ljunggren HG (2002) Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines. Int Immunol 14:1065–1074

    Article  PubMed  CAS  Google Scholar 

  • Arruda JL, Sweitzer S, Rutkowski MD, DeLeo JA (2000) Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain. Brain Res 879:216–225

    Article  PubMed  CAS  Google Scholar 

  • Babcock AA, Wirenfeldt M, Holm T, Nielsen HH, Dissing-Olesen L, Toft-Hansen H, Millward JM, Landmann R, Rivest S, Finsen B, Owens T (2006) Toll-like receptor 2 signalingin response to brain injury: an innate bridge to neuroinflammation. J Neurosci 2612826–12837

    Article  PubMed  CAS  Google Scholar 

  • Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87–107

    Article  PubMed  CAS  Google Scholar 

  • Boivin A, Pineau I, Barrette B, Filali M, Vallieres N, Rivest S, Lacroix S (2007) Toll-like receptor signaling is critical for Wallerian degeneration and functional recovery after peripheral nerve injury. J Neurosci 27:12565–12576

    Article  PubMed  CAS  Google Scholar 

  • Bolin LM, Verity AN, Silver JE, Shooter EM, Abrams JS (1995) Interleukin-6 production by Schwann cells and induction in sciatic nerve injury. J Neurochem 64:850–858

    Article  PubMed  CAS  Google Scholar 

  • Boyd JG, Gordon T (2003) Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol 183:610–619

    Article  PubMed  CAS  Google Scholar 

  • Broom DC, Samad TA, Kohno T, Tegeder I, Geisslinger G, Woolf CJ (2004) Cyclooxygenase 2 expression in the spared nerve injury model of neuropathic pain. Neuroscience 124:891–900

    Article  PubMed  CAS  Google Scholar 

  • Cameron JS, Alexopoulou L, Sloane JA, DiBernardo AB, Ma Y, Kosaras B, Flavell R, Strittmatter SM, Volpe J, Sidman R, Vartanian T (2007) Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals. J Neurosci 27:13033–13041

    Article  PubMed  CAS  Google Scholar 

  • Carroll SL, Frohnert PW (1998) Expression of JE (monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL/Wld(s) mice. J Neuropathol Exp Neurol 57:915–930

    Article  PubMed  CAS  Google Scholar 

  • Cavassani KA, Ishii M, Wen H, Schaller MA, Lincoln PM, Lukacs NW, Hogaboam CM, Kunkel SL (2008) TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J Exp Med 205:2609–2621

    Article  PubMed  CAS  Google Scholar 

  • Chakravarty S, Herkenham M (2005) Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci 25:1788–1796

    Article  PubMed  CAS  Google Scholar 

  • Chattopadhyay S, Myers RR, Janes J, Shubayev V (2007) Cytokine regulation of MMP-9 in peripheral glia: implications for pathological processes and pain in injured nerve. Brain Behav Immun 21:561–568

    Article  PubMed  CAS  Google Scholar 

  • Colburn RW, Rickman AJ, DeLeo JA (1999) The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp Neurol 157:289–304

    Article  PubMed  CAS  Google Scholar 

  • Coleman M (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6:889–898

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Cui JG, Holmin S, Mathiesen T, Meyerson BA, Linderoth B (2000) Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy. Pain 88:239–248

    Article  PubMed  CAS  Google Scholar 

  • Cunha TM, Verri WA Jr, Silva JS, Poole S, Cunha FQ, Ferreira SH (2005) A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc Natl Acad Sci USA 102:1755–1760

    Article  PubMed  CAS  Google Scholar 

  • Daffis S, Samuel MA, Suthar MS, Gale M, Diamond MS (2008) Toll-like receptor 3 has a protective role against west nile virus infection. J Virol 82:10349–10358

    Article  PubMed  CAS  Google Scholar 

  • Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87:149–158

    Article  PubMed  CAS  Google Scholar 

  • DeLeo JA, Colburn RW, Nichols M, Malhotra A (1996) Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. J Interferon Cytokine Res 16:695–700

    Article  PubMed  CAS  Google Scholar 

  • Dib-Hajj SD, Fjell J, Cummins TR, Zheng Z, Fried K, LaMotte R, Black JA, Waxman SG (1999) Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain 83:591–600

    Article  PubMed  CAS  Google Scholar 

  • Dowsing BJ, Romeo R, Morrison WA (2001) Expression of leukemia inhibitory factor in human nerve following injury. J Neurotrauma 18:1279–1287

    Article  PubMed  CAS  Google Scholar 

  • Gilmore SA, Skinner RD (1979) Intraspinal non-neuronal cellular responses to peripheral nerve injury. Anat Rec 194:369–387

    Article  PubMed  CAS  Google Scholar 

  • Guertin AD, Zhang DP, Mak KS, Alberta JA, Kim HA (2005) Microanatomy of axon/glial signaling during Wallerian degeneration. J Neurosci 25:3478–3487

    Article  PubMed  CAS  Google Scholar 

  • Hammarberg H, Piehl F, Cullheim S, Fjell J, Hokfelt T, Fried K (1996) GDNF mRNA in Schwann cells and DRG satellite cells after chronic sciatic nerve injury. Neuroreport 7:857–860

    Article  PubMed  CAS  Google Scholar 

  • Hanz S, Perlson E, Willis D, Zheng JQ, Massarwa R, Huerta JJ, Koltzenburg M, Kohler M, van-Minnen J, Twiss JL, Fainzilber M (2003) Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron 40:1095–1104

    Article  PubMed  CAS  Google Scholar 

  • Hashizume H, DeLeo JA, Colburn RW, Weinstein JN (2000) Spinal glial activation and cytokine expression after lumbar root injury in the rat. Spine 25:1206–1217

    Article  PubMed  CAS  Google Scholar 

  • Hu P, McLachlan EM (2003) Distinct functional types of macrophage in dorsal root ganglia and spinal nerves proximal to sciatic and spinal nerve transections in the rat. Exp Neurol 184:590–605

    Article  PubMed  Google Scholar 

  • Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, Sholar PW, Patel SJ, Crysdale NY, Harrison JA, Maier SF, Rice KC, Watkins LR (2008) Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci 28:20–29

    Article  PubMed  Google Scholar 

  • Jackson AC, Rossiter JP, Lafon M (2006) Expression of Toll-like receptor 3 in the human cerebellar cortex in rabies, herpes simplex encephalitis, and other neurological diseases. J Neurovirol 12:229–234

    Article  PubMed  CAS  Google Scholar 

  • Jou I, Lee JH, Park SY, Yoon HJ, Joe EH, Park EJ (2006) Gangliosides trigger inflammatory responses via TLR4 in brain glia. Am J Pathol 168:1619–1630

    Article  PubMed  CAS  Google Scholar 

  • Jungnickel J, Haase K, Konitzer J, Timmer M, Grothe C (2006) Faster nerve regeneration after sciatic nerve injury in mice over-expressing basic fibroblast growth factor. J Neurobiol 66:940–948

    Article  PubMed  CAS  Google Scholar 

  • Kang J, Rivest S (2007) MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis. J Cell Biol 179:1219–1230

    Article  PubMed  CAS  Google Scholar 

  • Karanth S, Yang G, Yeh J, Richardson PM (2006) Nature of signals that initiate the immune response during Wallerian degeneration of peripheral nerves. Exp Neurol 202:161–166

    Article  PubMed  CAS  Google Scholar 

  • Kariko K, Ni H, Capodici J, Lamphier M, Weissman D (2004) mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem 279:12542–12550

    Article  PubMed  CAS  Google Scholar 

  • Kerschensteiner M, Schwab ME, Lichtman JW, Misgeld T (2005) In vivo imaging of axonal degeneration and regeneration in the injured spinal cord. Nat Med 11:572–577

    Article  PubMed  CAS  Google Scholar 

  • Kim D, Kim MA, Cho IH, Kim MS, Lee S, Jo EK, Choi SY, Park K, Kim JS, Akira S, Na HS, Oh SB, Lee SJ (2007) A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J Biol Chem 282:14975–14983

    Article  PubMed  CAS  Google Scholar 

  • Kim JB, Sig Choi J, Yu YM, Nam K, Piao CS, Kim SW, Lee MH, Han PL, Park JS, Lee JK (2006) HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci 26:6413–6421

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Koltzenburg M (2005) Mechanisms of peripheral neuropathic pain. In: Hunt S, Koltzenburg M (eds) The neurobiology of pain (Molecular and Cellular Neurobiology Series), 1st edn. Oxford University Press, Oxford

    Google Scholar 

  • Kuhn G, Lie A, Wilms S, Muller HW (1993) Coexpression of PMP22 gene with MBP and P0 during de novo myelination and nerve repair. Glia 8:256–264

    Article  PubMed  CAS  Google Scholar 

  • Lafon M, Megret F, Lafage M, Prehaud C (2006) The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA. J Mol Neurosci 29:185–194

    Article  PubMed  CAS  Google Scholar 

  • Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, Watkins LR (2005) Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 115:71–83

    Article  PubMed  CAS  Google Scholar 

  • Lee H, Jo EK, Choi SY, Oh SB, Park K, Kim JS, Lee SJ (2006) Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3: implication in Wallerian degeneration. Biochem Biophys Res Commun 350:742–747

    Article  PubMed  CAS  Google Scholar 

  • Lee H, Park C, Cho IH, Kim HY, Jo EK, Lee S, Kho HS, Choi SY, Oh SB, Park K, Kim JS, Lee SJ (2007) Double-stranded RNA induces iNOS gene expression in Schwann cells, sensory neuronal death, and peripheral nerve demyelination. Glia 55:712–722

    Article  PubMed  Google Scholar 

  • Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, Rosenberg PA, Volpe JJ, Vartanian T (2002) The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci 22:2478–2486

    PubMed  CAS  Google Scholar 

  • Levy D, Hoke A, Zochodne DW (1999) Local expression of inducible nitric oxide synthase in an animal model of neuropathic pain. Neurosci Lett 260:207–209

    Article  PubMed  CAS  Google Scholar 

  • Levy D, Zochodne DW (1998) Local nitric oxide synthase activity in a model of neuropathic pain. Eur J Neurosci 10:1846–1855

    Article  PubMed  CAS  Google Scholar 

  • Li M, Carpio DF, Zheng Y, Bruzzo P, Singh V, Ouaaz F, Medzhitov RM, Beg AA (2001) An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J Immunol 166:7128–7135

    PubMed  CAS  Google Scholar 

  • Lindenlaub T, Teuteberg P, Hartung T, Sommer C (2000) Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury. Brain Res 866:15–22

    Article  PubMed  CAS  Google Scholar 

  • Lindwall C, Kanje M (2005) Retrograde axonal transport of JNK signaling molecules influence injury induced nuclear changes in p-c-Jun and ATF3 in adult rat sensory neurons. Mol Cell Neurosci 29:269–282

    Article  PubMed  CAS  Google Scholar 

  • Luk HW, Noble LJ, Werb Z (2003) Macrophages contribute to the maintenance of stable regenerating neurites following peripheral nerve injury. J Neurosci Res 73:644–658

    Article  PubMed  CAS  Google Scholar 

  • Ma W, Du W, Eisenach JC (2002) Role for both spinal cord COX-1, COX-2 in maintenance of mechanical hypersensitivity following peripheral nerve injury. Brain Res 937:94–99

    Article  PubMed  CAS  Google Scholar 

  • Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lu J, Kosaras B, Sidman RL, Volpe JJ, Vartanian T (2006) Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J Cell Biol 175:209–215

    Article  PubMed  CAS  Google Scholar 

  • Mack TG, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater T, Court F, Conforti L, Fernando FS, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci 4:1199–1206

    Article  PubMed  CAS  Google Scholar 

  • Malin SA, Molliver DC, Koerber HR, Cornuet P, Frye R, Albers KM, Davis BM (2006) Glial cell line-derived neurotrophic factor family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J Neurosci 26:8588–8599

    Article  PubMed  CAS  Google Scholar 

  • Malmberg AB, Bannon AW (1999) Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. In: Taylor G (ed) Current protocols in neuroscience. Wiley, Hoboken

    Google Scholar 

  • Marchand F, Perretti M, McMahon SB (2005) Role of the immune system in chronic pain. Nat Rev Neurosci 6:521–532

    Article  CAS  Google Scholar 

  • Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305

    Article  PubMed  CAS  Google Scholar 

  • McMahon SB, Cafferty WB, Marchand F (2005) Immune and glial cell factors as pain mediators and modulators. Exp Neurol 192:444–462

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145

    Article  PubMed  CAS  Google Scholar 

  • Meller ST, Pechman PS, Gebhart GF, Maves TJ (1992) Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat. Neuroscience 50:7–10

    Article  PubMed  CAS  Google Scholar 

  • Merskey H, Bogduk M (1994) Classification of chronic pain. IASP, Seattle

    Google Scholar 

  • Meyer M, Matsuoka I, Wetmore C, Olson L, Thoenen H (1992) Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. J Cell Biol 119:45–54

    Article  PubMed  CAS  Google Scholar 

  • Milligan ED, O’Connor KA, Nguyen KT, Armstrong CB, Twining C, Gaykema RP, Holguin A, Martin D, Maier SF, Watkins LR (2001) Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines. J Neurosci 21:2808–2819

    PubMed  CAS  Google Scholar 

  • Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT (1994) A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13:757–767

    Article  PubMed  CAS  Google Scholar 

  • Obata K, Katsura H, Miyoshi K, Kondo T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Akira S, Noguchi K (2008) Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury. J Neurochem 105:2249–2259

    Article  PubMed  CAS  Google Scholar 

  • Ohtori S, Takahashi K, Moriya H, Myers RR (2004) TNF-alpha and TNF-alpha receptor type 1 upregulation in glia and neurons after peripheral nerve injury: studies in murine DRG and spinal cord. Spine 29:1082–1088

    Article  PubMed  Google Scholar 

  • Oliveira RB, Ochoa MT, Sieling PA, Rea TH, Rambukkana A, Sarno EN, Modlin RL (2003) Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect Immun 71:1427–1433

    Article  PubMed  CAS  Google Scholar 

  • Pardo CA, McArthur JC, Griffin JW (2001) HIV neuropathy: insights in the pathology of HIV peripheral nerve disease. J Peripher Nerv Syst 6:21–27

    Article  PubMed  CAS  Google Scholar 

  • Park JS, Gamboni-Robertson F, He Q, Svetkauskaite D, Kim JY, Strassheim D, Sohn JW, Yamada S, Maruyama I, Banerjee A, Ishizaka A, Abraham E (2006) High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol 290:C917–C924

    Article  PubMed  CAS  Google Scholar 

  • Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088

    Article  PubMed  CAS  Google Scholar 

  • Prehaud C, Megret F, Lafage M, Lafon M (2005) Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon. J Virol 79:12893–12904

    Article  PubMed  CAS  Google Scholar 

  • Raghavendra V, Tanga F, DeLeo JA (2003) Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 306:624–630

    Article  PubMed  CAS  Google Scholar 

  • Ramer MS, Bisby MA (1997) Rapid sprouting of sympathetic axons in dorsal root ganglia of rats with a chronic constriction injury. Pain 70:237–244

    Article  PubMed  CAS  Google Scholar 

  • Rind HB, Butowt R, von Bartheld CS (2005) Synaptic targeting of retrogradely transported trophic factors in motoneurons: comparison of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, and cardiotrophin-1 with tetanus toxin. J Neurosci 25:539–549

    Article  PubMed  CAS  Google Scholar 

  • Salter MW, Woolf CJ (2005) Cellular and molecular mechanisms of central sensitization. In: Hunt S, Koltzenburg M (eds) The neurobiology of pain (Molecular and Cellular Neurobiology Series), 1st edn. Oxford University Press, Oxford

    Google Scholar 

  • Schweizer U, Gunnersen J, Karch C, Wiese S, Holtmann B, Takeda K, Akira S, Sendtner M (2002) Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult. J Cell Biol 156:287–297

    Article  PubMed  CAS  Google Scholar 

  • Seltzer Z, Dubner R, Shir Y (1990) A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43:205–218

    Article  PubMed  CAS  Google Scholar 

  • Shubayev VI, Angert M, Dolkas J, Campana WM, Palenscar K, Myers RR (2006) TNFalpha-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci 31:407–415

    Article  PubMed  CAS  Google Scholar 

  • Skundric DS, Bealmear B, Lisak RP (1997) Induced upregulation of IL-1, IL-1RA and IL-1R type I gene expression by Schwann cells. J Neuroimmunol 74:9–18

    Article  PubMed  CAS  Google Scholar 

  • Smiley ST, King JA, Hancock WW (2001) Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol 167:2887–2894

    PubMed  CAS  Google Scholar 

  • Smith GM, Rabinovsky ED, McManaman JL, Shine HD (1993) Temporal and spatial expression of ciliary neurotrophic factor after peripheral nerve injury. Exp Neurol 121:239–247

    Article  PubMed  CAS  Google Scholar 

  • Sommer C, Lindenlaub T, Teuteberg P, Schafers M, Hartung T, Toyka KV (2001) Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy. Brain Res 913:86–89

    Article  PubMed  CAS  Google Scholar 

  • Stoll G, Jander S, Myers RR (2002) Degeneration and regeneration of the peripheral nervous system: from Augustus Waller’s observations to neuroinflammation. J Peripher Nerv Syst 7:13–27

    Article  PubMed  Google Scholar 

  • Stoll G, Jung S, Jander S, van der Meide P, Hartung HP (1993) Tumor necrosis factor-alpha in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system. J Neuroimmunol 45:175–182

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, Bennett GJ, Kajander KC (1990) Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. Pain 42:205–213

    Article  PubMed  CAS  Google Scholar 

  • Sweitzer S, Martin D, DeLeo JA (2001) Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain. Neuroscience 103:529–539

    Article  PubMed  CAS  Google Scholar 

  • Takahashi M, Kawaguchi M, Shimada K, Konishi N, Furuya H, Nakashima T (2004) Cyclooxygenase-2 expression in Schwann cells and macrophages in the sciatic nerve after single spinal nerve injury in rats. Neurosci Lett 363:203–206

    Article  PubMed  CAS  Google Scholar 

  • Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, Lathia JD, Siler DA, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP (2007) Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci USA 104:13798–13803

    Article  PubMed  CAS  Google Scholar 

  • Tanga FY, Nutile-McMenemy N, DeLeo JA (2005) The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA 102:5856–5861

    Article  PubMed  CAS  Google Scholar 

  • Tanga FY, Raghavendra V, DeLeo JA (2004) Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int 45:397–407

    Article  PubMed  CAS  Google Scholar 

  • Taskinen HS, Roytta M (2000) Increased expression of chemokines (MCP-1, MIP-1alpha, RANTES) after peripheral nerve transection. J Peripher Nerv Syst 5:75–81

    Article  PubMed  CAS  Google Scholar 

  • Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC (2002) Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 195:99–111

    Article  PubMed  CAS  Google Scholar 

  • Tofaris GK, Patterson PH, Jessen KR, Mirsky R (2002) Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. J Neurosci 22:6696–6703

    PubMed  CAS  Google Scholar 

  • Town T, Jeng D, Alexopoulou L, Tan J, Flavell RA (2006) Microglia recognize double-stranded RNA via TLR3. J Immunol 176:3804–3812

    PubMed  CAS  Google Scholar 

  • Tsuda M, Inoue K, Salter MW (2005) Neuropathic pain and spinal microglia: a big problem from molecules in “small” glia. Trends Neurosci 28:101–107

    Article  PubMed  CAS  Google Scholar 

  • Vabulas RM, Wagner H, Schild H (2002) Heat shock proteins as ligands of toll-like receptors. Curr Top Microbiol Immunol 270:169–184

    Article  PubMed  CAS  Google Scholar 

  • Vikman KS, Duggan AW, Siddall PJ (2007) Interferon-gamma induced disruption of GABAergic inhibition in the spinal dorsal horn in vivo. Pain 133:18–28

    Article  PubMed  CAS  Google Scholar 

  • Wadachi R, Hargreaves KM (2006) Trigeminal nociceptors express TLR-4 and CD14: a mechanism for pain due to infection. J Dent Res 85:49–53

    Article  PubMed  CAS  Google Scholar 

  • Wagner R, Myers RR (1996) Schwann cells produce tumor necrosis factor alpha: expression in injured and non-injured nerves. Neuroscience 73:625–629

    Article  PubMed  CAS  Google Scholar 

  • Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24:450–455

    Article  PubMed  CAS  Google Scholar 

  • Yang EK, Takimoto K, Hayashi Y, de Groat WC, Yoshimura N (2004) Altered expression of potassium channel subunit mRNA and alpha-dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy. Neuroscience 123:867–874

    Article  PubMed  CAS  Google Scholar 

  • Yoon HJ, Jeon SB, Suk K, Choi DK, Hong YJ, Park EJ (2008) Contribution of TLR2 to the initiation of ganglioside-triggered inflammatory signaling. Mol Cells 25:99–104

    PubMed  CAS  Google Scholar 

  • Yura Y (2000) Orofacial alpha herpesvirus infection. Nippon Rinsho 58:912–917

    PubMed  CAS  Google Scholar 

  • Zochodne DW, Levy D, Zwiers H, Sun H, Rubin I, Cheng C, Lauritzen M (1999) Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected peripheral nerves. Neuroscience 91:1515–1527

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a Korea Research Foundation Grant (KRF-2008-313-C00749) and a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST) (R01-2007-000-10243-0, R11-2008-036-02003-0).

Author information

Authors and Affiliations

  1. Program in Molecular and Cellular Neuroscience, DRI, BK21, and Department of Oral Physiology, School of Dentistry, Seoul National University, Seoul, Republic of Korea

    Donghoon Kim & Sung Joong Lee

  2. Department of Microbiology, School of Systems Biology, Chungnam National University, Daejoen, Republic of Korea

    Soojin Lee

Authors
  1. Donghoon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soojin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung Joong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung Joong Lee .

Editor information

Editors and Affiliations

  1. Dept. Pathology & Microbiology, University of Nebraska Medical Center, S. 42nd St. 600 , Omaha, 68198-3135, U.S.A.

    Tammy Kielian

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kim, D., Lee, S., Lee, S.J. (2009). Toll-Like Receptors in Peripheral Nerve Injury and Neuropathic Pain. In: Kielian, T. (eds) Toll-like Receptors: Roles in Infection and Neuropathology. Current Topics in Microbiology and Immunology, vol 336. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00549-7_10

Download citation

Publish with us

Policies and ethics

Search

Navigation