Abstract
Injuries typically result in the development of neuropathic pain, which decreases in parallel with wound healing. However, the pain may remain after the injury appears to have healed, which is generally associated with an ongoing underlying pro-inflammatory state. Injury induces many cells to release factors that contribute to the development of a pro-inflammatory state, which is considered an essential first step towards wound healing. However, pain elimination requires a transition of the injury site from pro- to anti-inflammatory. Therefore, developing techniques that eliminate chronic pain require an understanding of the cells resident at and recruited to injury sites, the factors they release, that promote a pro-inflammatory state, and promote the subsequent transition of that site to be anti-inflammatory. Although a relatively large number of cells, factors, and gene expression changes are involved in these processes, it may be possible to control a relatively small number of them leading to the reduction and elimination of chronic neuropathic pain. This first of two papers examines the roles of the most salient cells and mediators associated with the development and maintenance of chronic neuropathic pain. The following paper examines the cells and mediators involved in reducing and eliminating chronic neuropathic pain.
Similar content being viewed by others
References
Vranken JH (2009) Mechanisms and treatment of neuropathic pain. Cent Nerv Syst Agents Med Chem 9:71–78
Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, Freeman R, Truini A et al (2017) Neuropathic pain. Nat Rev Dis Primers 3:17002. https://doi.org/10.1038/nrdp.2017.2
Yawn BP, Wollan PC, Weingarten TN, Watson JC, Hooten WM, Melton LJ 3rd. (2009) The prevalence of neuropathic pain: clinical evaluation compared with screening tools in a community population. Pain Med 10:586–593. https://doi.org/10.1111/j.1526-4637.2009.00588.x
DiBonaventura MD, Sadosky A, Concialdi K, Hopps M, Kudel I, Parsons B, Cappelleri JC, Hlavacek P et al (2017) The prevalence of probable neuropathic pain in the US: results from a multimodal general-population health survey. J Pain Res 10:2525–2538. https://doi.org/10.2147/JPR.S127014
Wei Z, Fei Y, Su W, Chen G (2019) Emerging role of Schwann cells in neuropathic pain: receptors, glial mediators and myelination. Front Cell Neurosci 13:116. https://doi.org/10.3389/fncel.2019.00116
Campbell JN, Meyer RA (2006) Mechanisms of neuropathic pain. Neuron. 52:77–92. https://doi.org/10.1016/j.neuron.2006.09.021
Meacham K, Shepherd A, Mohapatra DP, Haroutounian S. (2017) Neuropathic pain: central vs. peripheral mechanisms. Curr Pain Headache Rep. 21:28. https://doi.org/10.1007/s11916-017-0629-5
Xie WR, Deng H, Li H, Bowen TL, Strong JA, Zhang JM (2006) Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia. Neuroscience. 142:809–822. https://doi.org/10.1016/j.neuroscience.2006.06.045
Zhang JM, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45:27–37. https://doi.org/10.1097/AIA.0b013e318034194e
Berta T, Perrin FE, Pertin M, Tonello R, Liu YC, Chamessian A, Kato AC, Ji RR et al (2017) Gene expression profiling of cutaneous injured and non-injured nociceptors in SNI animal model of neuropathic pain. Sci Rep 7:9367. https://doi.org/10.1038/s41598-017-08865-3
Wu S, Marie Lutz B, Miao X, Liang L, Mo K, Chang YJ, Du P, Soteropoulos P et al (2016) Dorsal root ganglion transcriptome analysis following peripheral nerve injury in mice. Mol Pain 12. https://doi.org/10.1177/1744806916629048
Shamash S, Reichert F, Rotshenker S (2002) The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci 22:3052–3060 https://doi.org/20026249
Zedler S, Faist E (2006) The impact of endogenous triggers on trauma-associated inflammation. Curr Opin Crit Care 12:595–601. https://doi.org/10.1097/MCC.0b013e3280106806
Rotshenker S (2011) Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 8:109. https://doi.org/10.1186/1742-2094-8-109
Kawai T, Akira S (2007) TLR signaling. Semin Immunol 19:24–32. https://doi.org/10.1016/j.smim.2006.12.004
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. https://doi.org/10.1016/j.bbrc.2006.09.108
Martini R, Fischer S, Lopez-Vales R, David S (2008) Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease. Glia. 56:1566–1577. https://doi.org/10.1002/glia.20766
Pineau I, Lacroix S (2009) Endogenous signals initiating inflammation in the injured nervous system. Glia. 57:351–361. https://doi.org/10.1002/glia.20763
DeFrancesco-Lisowitz A, Lindborg JA, Niemi JP, Zigmond RE (2015) The neuroimmunology of degeneration and regeneration in the peripheral nervous system. Neuroscience. 302:174–203. https://doi.org/10.1016/j.neuroscience.2014.09.027
Gaudet AD, Popovich PG, Ramer MS (2011) Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammation 8:110. https://doi.org/10.1186/1742-2094-8-110
Palomo J, Dietrich D, Martin P, Palmer G, Gabay C (2015) The interleukin (IL)-1 cytokine family--balance between agonists and antagonists in inflammatory diseases. Cytokine. 76:25–37. https://doi.org/10.1016/j.cyto.2015.06.017
De S, Trigueros MA, Kalyvas A, David S (2003) Phospholipase A2 plays an important role in myelin breakdown and phagocytosis during Wallerian degeneration. Mol Cell Neurosci 24:753–765
Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR et al (2008) Nociceptors are interleukin-1beta sensors. J Neurosci 28:14062–14073. https://doi.org/10.1523/JNEUROSCI.3795-08.2008
Uceyler N, Tscharke A, Sommer C (2007) Early cytokine expression in mouse sciatic nerve after chronic constriction nerve injury depends on calpain. Brain Behav Immun 21:553–560. https://doi.org/10.1016/j.bbi.2006.10.003
Wu R, Chen B, Jia X, Qiu Y, Liu M, Huang C, Feng J, Wu Q (2019) Interleukin-1beta influences functional regeneration following nerve injury in mice through nuclear factor-kappaB signaling pathway. Immunology. 156:235–248. https://doi.org/10.1111/imm.13022
Ozaktay AC, Kallakuri S, Takebayashi T, Cavanaugh JM, Asik I, DeLeo JA, Weinstein JN (2006) Effects of interleukin-1 beta, interleukin-6, and tumor necrosis factor on sensitivity of dorsal root ganglion and peripheral receptive fields in rats. Eur Spine J 15:1529–1537. https://doi.org/10.1007/s00586-005-0058-8
Mietto BS, Jurgensen S, Alves L, Pecli C, Narciso MS, Assuncao-Miranda I, Villa-Verde DM, de Souza Lima FR et al (2013) Lack of galectin-3 speeds Wallerian degeneration by altering TLR and pro-inflammatory cytokine expressions in injured sciatic nerve. Eur J Neurosci 37:1682–1690. https://doi.org/10.1111/ejn.12161
Rider P, Carmi Y, Guttman O, Braiman A, Cohen I, Voronov E, White MR, Dinarello CA et al (2011) IL-1alpha and IL-1beta recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol 187:4835–4843. https://doi.org/10.4049/jimmunol.1102048
Schenk M, Fabri M, Krutzik SR, Lee DJ, Vu DM, Sieling PA, Montoya D, Liu PT et al (2014) Interleukin-1beta triggers the differentiation of macrophages with enhanced capacity to present mycobacterial antigen to T cells. Immunology. 141:174–180. https://doi.org/10.1111/imm.12167
Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B, van der Meer JH, van de Veerdonk FL, Ferwerda G et al (2009) Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood. 113:2324–2335. https://doi.org/10.1182/blood-2008-03-146720
Sung CS, Wen ZH, Chang WK, Ho ST, Tsai SK, Chang YC, Wong CS (2004) Intrathecal interleukin-1beta administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord. Brain Res 1015:145–153. https://doi.org/10.1016/j.brainres.2004.04.068
Schafers M, Sorkin L (2008) Effect of cytokines on neuronal excitability. Neurosci Lett 437:188–193. https://doi.org/10.1016/j.neulet.2008.03.052
Perrin FE, Lacroix S, Aviles-Trigueros M, David S (2005) Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta in Wallerian degeneration. Brain. 128:854–866. https://doi.org/10.1093/brain/awh407
Cunha JM, Cunha FQ, Poole S, Ferreira SH (2000) Cytokine-mediated inflammatory hyperalgesia limited by interleukin-1 receptor antagonist. Br J Pharmacol 130:1418–1424. https://doi.org/10.1038/sj.bjp.0703434
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
Chistiakov DA, Voronova NV, Chistiakov PA (2008) The crucial role of IL-2/IL-2RA-mediated immune regulation in the pathogenesis of type 1 diabetes, an evidence coming from genetic and animal model studies. Immunol Lett 118:1–5. https://doi.org/10.1016/j.imlet.2008.03.002
Hoyer KK, Dooms H, Barron L, Abbas AK (2008) Interleukin-2 in the development and control of inflammatory disease. Immunol Rev 226:19–28. https://doi.org/10.1111/j.1600-065X.2008.00697.x
Seelaender M, Neto JC, Pimentel GD, Goldszmid RS, Lira FS (2015) Inflammation in the disease: mechanism and therapies 2014. Mediat Inflamm 2015:169852. https://doi.org/10.1155/2015/169852
Lan RY, Selmi C, Gershwin ME (2008) The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2). J Autoimmun 31:7–12. https://doi.org/10.1016/j.jaut.2008.03.002
Sommer C, Kress M (2004) Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett 361:184–187. https://doi.org/10.1016/j.neulet.2003.12.007
Ko JS, Eddinger KA, Angert M, Chernov AV, Dolkas J, Strongin AY, Yaksh TL, Shubayev VI (2016) Spinal activity of interleukin 6 mediates myelin basic protein-induced allodynia. Brain Behav Immun 56:378–389. https://doi.org/10.1016/j.bbi.2016.03.003
Nadeau S, Filali M, Zhang J, Kerr BJ, Rivest S, Soulet D, Iwakura Y, de Rivero Vaccari JP et al (2011) Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1beta and TNF: implications for neuropathic pain. J Neurosci 31:12533–12542. https://doi.org/10.1523/JNEUROSCI.2840-11.2011
Zang Y, Chen SX, Liao GJ, Zhu HQ, Wei XH, Cui Y, Na XD, Pang RP et al (2015) Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons. Brain Behav Immun 44:37–47. https://doi.org/10.1016/j.bbi.2014.08.003
Menezes GD, Goulart VG, Espirito-Santo S, Oliveira-Silva P, Serfaty CA, Campello-Costa P (2016) Intravitreous injection of interleukin-6 leads to a sprouting in the retinotectal pathway at different stages of development. Neuroimmunomodulation. 23:81–87. https://doi.org/10.1159/000444529
Zhou YQ, Liu Z, Liu ZH, Chen SP, Li M, Shahveranov A, Ye DW, Tian YK (2016) Interleukin-6: an emerging regulator of pathological pain. J Neuroinflammation 13:141. https://doi.org/10.1186/s12974-016-0607-6
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. https://doi.org/10.1016/s0006-8993(00)02807-9
De Jongh RF, Vissers KC, Meert TF, Booij LH, De Deyne CS, Heylen RJ (2003) The role of interleukin-6 in nociception and pain. Anesth Analg 96:1096–1103 table of contents
Martucci C, Trovato AE, Costa B, Borsani E, Franchi S, Magnaghi V, Panerai AE, Rodella LF et al (2008) The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1 beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice. Pain 137:81–95. https://doi.org/10.1016/j.pain.2007.08.017
Shubayev VI, Myers RR (2000) Upregulation and interaction of TNFalpha and gelatinases A and B in painful peripheral nerve injury. Brain Res 855:83–89
Tao T, Ji Y, Cheng C, Yang H, Liu H, Sun L, Qin Y, Yang J et al (2009) Tumor necrosis factor-alpha inhibits Schwann cell proliferation by up-regulating Src-suppressed protein kinase C substrate expression. J Neurochem 111:647–655. https://doi.org/10.1111/j.1471-4159.2009.06346.x
Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 127:514–525. https://doi.org/10.1038/sj.jid.5700701
Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology. 115:1–20. https://doi.org/10.1111/j.1365-2567.2005.02143.x
Chadwick W, Magnus T, Martin B, Keselman A, Mattson MP, Maudsley S (2008) Targeting TNF-alpha receptors for neurotherapeutics. Trends Neurosci 31:504–511. https://doi.org/10.1016/j.tins.2008.07.005
Romero-Sandoval EA, McCall C, Eisenach JC (2005) Alpha2-adrenoceptor stimulation transforms immune responses in neuritis and blocks neuritis-induced pain. J Neurosci 25:8988–8994. https://doi.org/10.1523/JNEUROSCI.2995-05.2005
Liefner M, Siebert H, Sachse T, Michel U, Kollias G, Bruck W (2000) The role of TNF-alpha during Wallerian degeneration. J Neuroimmunol 108:147–152
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 (Phila Pa 1976) 29:1082–1088
Stellwagen D, Malenka RC (2006) Synaptic scaling mediated by glial TNF-alpha. Nature. 440:1054–1059. https://doi.org/10.1038/nature04671
Sacerdote P, Franchi S, Trovato AE, Valsecchi AE, Panerai AE, Colleoni M (2008) Transient early expression of TNF-alpha in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy. Neurosci Lett 436:210–213. https://doi.org/10.1016/j.neulet.2008.03.023
Zhang JM, Li H, Liu B, Brull SJ (2002) Acute topical application of tumor necrosis factor alpha evokes protein kinase A-dependent responses in rat sensory neurons. J Neurophysiol 88:1387–1392. https://doi.org/10.1152/jn.2002.88.3.1387
Khan AA, Diogenes A, Jeske NA, Henry MA, Akopian A, Hargreaves KM (2008) Tumor necrosis factor alpha enhances the sensitivity of rat trigeminal neurons to capsaicin. Neuroscience. 155:503–509. https://doi.org/10.1016/j.neuroscience.2008.05.036
Sorkin LS, Doom CM (2000) Epineurial application of TNF elicits an acute mechanical hyperalgesia in the awake rat. J Peripher Nerv Syst 5:96–100
Gruber-Schoffnegger D, Drdla-Schutting R, Honigsperger C, Wunderbaldinger G, Gassner M, Sandkuhler J (2013) Induction of thermal hyperalgesia and synaptic long-term potentiation in the spinal cord lamina I by TNF-alpha and IL-1beta is mediated by glial cells. J Neurosci 33:6540–6551. https://doi.org/10.1523/JNEUROSCI.5087-12.2013
Woolf CJ, Allchorne A, Safieh-Garabedian B, Poole S (1997) Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. Br J Pharmacol 121:417–424. https://doi.org/10.1038/sj.bjp.0701148
Wagner R, Myers RR (1996) Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport 7:2897–2901
Schafers M, Svensson CI, Sommer C, Sorkin LS (2003) Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons. J Neurosci 23:2517–2521
Charles P, Elliott MJ, Davis D, Potter A, Kalden JR, Antoni C, Breedveld FC, Smolen JS et al (1999) Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis. J Immunol 163:1521–1528
Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J (1995) Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine. 7:251–259. https://doi.org/10.1006/cyto.1995.0029
Baert FJ, D'Haens GR, Peeters M, Hiele MI, Schaible TF, Shealy D, Geboes K, Rutgeerts PJ (1999) Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. Gastroenterology. 116:22–28
Einheber S, Hannocks MJ, Metz CN, Rifkin DB, Salzer JL (1995) Transforming growth factor-beta 1 regulates axon/Schwann cell interactions. J Cell Biol 129:443–458
Unsicker K, Flanders KC, Cissel DS, Lafyatis R, Sporn MB (1991) Transforming growth factor beta isoforms in the adult rat central and peripheral nervous system. Neuroscience. 44:613–625
Eppley BL, Woodell JE, Higgins J (2004) Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 114:1502–1508
Rolfe KJ, Richardson J, Vigor C, Irvine LM, Grobbelaar AO, Linge C (2007) A role for TGF-beta1-induced cellular responses during wound healing of the non-scarring early human fetus? J Invest Dermatol 127:2656–2667. https://doi.org/10.1038/sj.jid.5700951
Diegelmann RF, Evans MC (2004) Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci 9:283–289
Nikolidakis D, Jansen JA (2008) The biology of platelet-rich plasma and its application in oral surgery: literature review. Tissue Eng Part B Rev 14:249–258. https://doi.org/10.1089/ten.teb.2008.0062
Li AG, Wang D, Feng XH, Wang XJ (2004) Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO J 23:1770–1781. https://doi.org/10.1038/sj.emboj.7600183
Letterio JJ, Roberts AB (1998) Regulation of immune responses by TGF-beta. Annu Rev Immunol 16:137–161. https://doi.org/10.1146/annurev.immunol.16.1.137
Marek A, Brodzicki J, Liberek A, Korzon M (2002) TGF-beta (transforming growth factor-beta) in chronic inflammatory conditions - a new diagnostic and prognostic marker? Med Sci Monit 8:RA145–RA151
Lawrence T, Willoughby DA, Gilroy DW (2002) Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol 2:787–795. https://doi.org/10.1038/nri915
Borkowski TA, Letterio JJ, Mackall CL, Saitoh A, Farr AG, Wang XJ, Roop DR, Gress RE et al (1997) Langerhans cells in the TGF beta 1 null mouse. Adv Exp Med Biol 417:307–310
Tonnesen MG, Feng X, Clark RA (2000) Angiogenesis in wound healing. J Investig Dermatol Symp Proc 5:40–46. https://doi.org/10.1046/j.1087-0024.2000.00014.x
Riedel K, Riedel F, Goessler UR, Germann G, Sauerbier M (2007) Tgf-beta antisense therapy increases angiogenic potential in human keratinocytes in vitro. Arch Med Res 38:45–51. https://doi.org/10.1016/j.arcmed.2006.04.010
Morrissey JH, Choi SH, Smith SA (2012) Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation. Blood. 119:5972–5979. https://doi.org/10.1182/blood-2012-03-306605
Smith SA, Morrissey JH (2014) Polyphosphate: a new player in the field of hemostasis. Curr Opin Hematol 21:388–394. https://doi.org/10.1097/MOH.0000000000000069
Travers RJ, Smith SA, Morrissey JH (2015) Polyphosphate, platelets, and coagulation. Int J Lab Hematol 37(Suppl 1):31–35. https://doi.org/10.1111/ijlh.12349
Bae JS, Lee W, Rezaie AR (2012) Polyphosphate elicits pro-inflammatory responses that are counteracted by activated protein C in both cellular and animal models. J Thromb Haemost 10:1145–1151. https://doi.org/10.1111/j.1538-7836.2012.04671.x
Gora S, Lambeau G, Bollinger JG, Gelb M, Ninio E, Karabina SA (2006) The proinflammatory mediator platelet activating factor is an effective substrate for human group X secreted phospholipase A2. Biochim Biophys Acta 1761:1093–1099. https://doi.org/10.1016/j.bbalip.2006.08.004
Dinarvand P, Hassanian SM, Qureshi SH, Manithody C, Eissenberg JC, Yang L, Rezaie AR (2014) Polyphosphate amplifies proinflammatory responses of nuclear proteins through interaction with receptor for advanced glycation end products and P2Y1 purinergic receptor. Blood. 123:935–945. https://doi.org/10.1182/blood-2013-09-529602
Hassanian SM, Dinarvand P, Smith SA, Rezaie AR (2015) Inorganic polyphosphate elicits pro-inflammatory responses through activation of the mammalian target of rapamycin complexes 1 and 2 in vascular endothelial cells. J Thromb Haemost 13:860–871. https://doi.org/10.1111/jth.12899
Tak PP, Firestein GS (2001) NF-kappaB: a key role in inflammatory diseases. J Clin Invest 107:7–11. https://doi.org/10.1172/JCI11830
Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P, Esmon NL, Esmon CT (2011) Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood. 118:1952–1961. https://doi.org/10.1182/blood-2011-03-343061
Beaulieu LM, Freedman JE (2011) Inflammation & the platelet histone trap. Blood. 118:1714–1715. https://doi.org/10.1182/blood-2011-06-362764
Bordon Y (2018) Innate immunity: platelets on the prowl. Nat Rev Immunol 18:3. https://doi.org/10.1038/nri.2017.147
Conti G, Rostami A, Scarpini E, Baron P, Galimberti D, Bresolin N, Contri M, Palumbo C et al (2004) Inducible nitric oxide synthase (iNOS) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system. Exp Neurol 187:350–358. https://doi.org/10.1016/j.expneurol.2004.01.026
Laroux FS, Pavlick KP, Hines IN, Kawachi S, Harada H, Bharwani S, Hoffman JM, Grisham MB (2001) Role of nitric oxide in inflammation. Acta Physiol Scand 173:113–118. https://doi.org/10.1046/j.1365-201X.2001.00891.x
De Alba J, Clayton NM, Collins SD, Colthup P, Chessell I, Knowles RG (2006) GW274150, a novel and highly selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), shows analgesic effects in rat models of inflammatory and neuropathic pain. Pain. 120:170–181. https://doi.org/10.1016/j.pain.2005.10.028
Makuch W, Mika J, Rojewska E, Zychowska M, Przewlocka B (2013) Effects of selective and non-selective inhibitors of nitric oxide synthase on morphine- and endomorphin-1-induced analgesia in acute and neuropathic pain in rats. Neuropharmacology 75:445–457. https://doi.org/10.1016/j.neuropharm.2013.08.031
Conti A, Miscusi M, Cardali S, Germano A, Suzuki H, Cuzzocrea S, Tomasello F (2007) Nitric oxide in the injured spinal cord: synthases cross-talk, oxidative stress and inflammation. Brain Res Rev 54:205–218
Lehmann HC, Kohne A, Meyer zu Horste G, Dehmel T, Kiehl O, Hartung HP, Kastenbauer S, Kieseier BC (2007) Role of nitric oxide as mediator of nerve injury in inflammatory neuropathies. J Neuropathol Exp Neurol 66:305–312. https://doi.org/10.1097/nen.0b013e3180408daa
Chatzipanteli K, Garcia R, Marcillo AE, Loor KE, Kraydieh S, Dietrich WD (2002) Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury: effect of aminoguanidine treatment. J Neurotrauma 19:639–651. https://doi.org/10.1089/089771502753754109
Bode JG, Ehlting C, Haussinger D (2012) The macrophage response towards LPS and its control through the p38(MAPK)-STAT3 axis. Cell Signal 24:1185–1194. https://doi.org/10.1016/j.cellsig.2012.01.018
Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ (2005) Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochem Biophys Res Commun 334:1092–1101. https://doi.org/10.1016/j.bbrc.2005.06.202
Claar D, Hartert TV, Peebles RS Jr (2015) The role of prostaglandins in allergic lung inflammation and asthma. Expert Rev Respir Med 9:55–72. https://doi.org/10.1586/17476348.2015.992783
Loynes CA, Lee JA, Robertson AL, Steel MJ, Ellett F, Feng Y, Levy BD, Whyte MKB et al (2018) PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo. Sci Adv 4:eaar8320. https://doi.org/10.1126/sciadv.aar8320
Kawabata A (2011) Prostaglandin E2 and pain--an update. Biol Pharm Bull 34:1170–1173
Ricciotti E, FitzGerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31:986–1000. https://doi.org/10.1161/ATVBAHA.110.207449
Ricciotti E, Yu Y, Grosser T, Fitzgerald GA (2013) COX-2, the dominant source of prostacyclin. Proc Natl Acad Sci U S A 110:E183. https://doi.org/10.1073/pnas.1219073110
Lin CR, Amaya F, Barrett L, Wang H, Takada J, Samad TA, Woolf CJ (2006) Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity. J Pharmacol Exp Ther 319:1096–1103. https://doi.org/10.1124/jpet.106.105569
Southall MD, Vasko MR (2001) Prostaglandin receptor subtypes, EP3C and EP4, mediate the prostaglandin E2-induced cAMP production and sensitization of sensory neurons. J Biol Chem 276:16083–16091. https://doi.org/10.1074/jbc.M011408200
Kassuya CA, Ferreira J, Claudino RF, Calixto JB (2007) Intraplantar PGE2 causes nociceptive behaviour and mechanical allodynia: the role of prostanoid E receptors and protein kinases. Br J Pharmacol 150:727–737. https://doi.org/10.1038/sj.bjp.0707149
Garrido D, Chanteloup NK, Trotereau A, Lion A, Bailleul G, Esnault E, Trapp S, Quere P et al (2017) Characterization of the Phospholipid Platelet-Activating Factor As a Mediator of Inflammation in Chickens. Front Vet Sci 4:226. https://doi.org/10.3389/fvets.2017.00226
Gomez FP, Rodriguez-Roisin R (2000) Platelet-activating factor antagonists: current status in asthma. Biodrugs. 14:21–30
McIntyre TM, Prescott SM, Stafforini DM (2009) The emerging roles of PAF acetylhydrolase. J Lipid Res 50(Suppl):S255–S259. https://doi.org/10.1194/jlr.R800024-JLR200
Papakonstantinou VD, Lagopati N, Tsilibary EC, Demopoulos CA, Philippopoulos AI (2017) A review on platelet activating factor inhibitors: could a new class of potent metal-based anti-inflammatory drugs induce anticancer properties? Bioinorg Chem Appl 2017:6947034. https://doi.org/10.1155/2017/6947034
Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13:159–175. https://doi.org/10.1038/nri3399
Babcock AA, Toft-Hansen H, Owens T (2008) Signaling through MyD88 regulates leukocyte recruitment after brain injury. J Immunol 181:6481–6490. https://doi.org/10.4049/jimmunol.181.9.6481
Leick M, Azcutia V, Newton G, Luscinskas FW (2014) Leukocyte recruitment in inflammation: basic concepts and new mechanistic insights based on new models and microscopic imaging technologies. Cell Tissue Res 355:647–656. https://doi.org/10.1007/s00441-014-1809-9
Rittner HL, Brack A (2007) Leukocytes as mediators of pain and analgesia. Curr Rheumatol Rep 9:503–510
Rittner HL, Machelska H, Stein C (2005) Leukocytes in the regulation of pain and analgesia. J Leukoc Biol 78:1215–1222
Jeanjean AP, Moussaoui SM, Maloteaux JM, Laduron PM (1995) Interleukin-1 beta induces long-term increase of axonally transported opiate receptors and substance P. Neuroscience. 68:151–157
Schweizer A, Feige U, Fontana A, Muller K, Dinarello CA (1988) Interleukin-1 enhances pain reflexes. Mediation through increased prostaglandin E2 levels. Agents Actions 25:246–251
Cao L, DeLeo JA (2008) CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur J Immunol 38:448–458. https://doi.org/10.1002/eji.200737485
Lindborg JA, Mack M, Zigmond RE (2017) Neutrophils are critical for myelin removal in a peripheral nerve injury model of wallerian degeneration. J Neurosci 37:10258–10277. https://doi.org/10.1523/JNEUROSCI.2085-17.2017
Hatanaka E, Monteagudo PT, Marrocos MS, Campa A (2006) Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes. Clin Exp Immunol 146:443–447. https://doi.org/10.1111/j.1365-2249.2006.03229.x
Hatanaka E, Furlaneto CJ, Ribeiro FP, Souza GM, Campa A (2004) Serum amyloid A-induced mRNA expression and release of tumor necrosis factor-alpha (TNF-alpha) in human neutrophils. Immunol Lett 91:33–37
Gougerot-Pocidalo MA, el Benna J, Elbim C, Chollet-Martin S, Dang MC (2002) Regulation of human neutrophil oxidative burst by pro- and anti-inflammatory cytokines. J Soc Biol 196:37–46
Wang ZQ, Porreca F, Cuzzocrea S, Galen K, Lightfoot R, Masini E, Muscoli C, Mollace V et al (2004) A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther 309:869–878. https://doi.org/10.1124/jpet.103.064154
Marks PA, Richon VM, Rifkind RA (2000) Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst 92:1210–1216
Alhamdi Y, Toh CH (2016) The role of extracellular histones in haematological disorders. Br J Haematol 173:805–811. https://doi.org/10.1111/bjh.14077
Abrams ST, Zhang N, Manson J, Liu T, Dart C, Baluwa F, Wang SS, Brohi K et al (2013) Circulating histones are mediators of trauma-associated lung injury. Am J Respir Crit Care Med 187:160–169. https://doi.org/10.1164/rccm.201206-1037OC
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science. 303:1532–1535. https://doi.org/10.1126/science.1092385
Chen R, Kang R, Fan XG, Tang D (2014) Release and activity of histone in diseases. Cell Death Dis 5:e1370. https://doi.org/10.1038/cddis.2014.337
Xu J, Zhang X, Monestier M, Esmon NL, Esmon CT (2011) Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. J Immunol 187:2626–2631. https://doi.org/10.4049/jimmunol.1003930
Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V (2015) Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349:316–320. https://doi.org/10.1126/science.aaa8064
Chatterjea D, Martinov T (2015) Mast cells: versatile gatekeepers of pain. Mol Immunol 63:38–44. https://doi.org/10.1016/j.molimm.2014.03.001
Ren K, Dubner R (2010) Interactions between the immune and nervous systems in pain. Nat Med 16:1267–1276. https://doi.org/10.1038/nm.2234
Heron A, Dubayle D (2013) A focus on mast cells and pain. J Neuroimmunol 264:1–7. https://doi.org/10.1016/j.jneuroim.2013.09.018
Mobarakeh JI, Sakurada S, Katsuyama S, Kutsuwa M, Kuramasu A, Lin ZY, Watanabe T, Hashimoto Y et al (2000) Role of histamine H(1) receptor in pain perception: a study of the receptor gene knockout mice. Eur J Pharmacol 391:81–89
Zuo Y, Perkins NM, Tracey DJ, Geczy CL (2003) Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain. 105:467–479
Parada CA, Tambeli CH, Cunha FQ, Ferreira SH (2001) The major role of peripheral release of histamine and 5-hydroxytryptamine in formalin-induced nociception. Neuroscience. 102:937–944
Wang Y, Mao L, Zhang L, Zhang L, Yang M, Zhang Z, Li D, Fan C et al (2016) Adoptive Regulatory T-cell Therapy Attenuates Subarachnoid Hemor-rhage-induced Cerebral Inflammation by Suppressing TLR4/NF-B Signaling Pathway. Curr Neurovasc Res 13:121–126
Sun T, Song WG, Fu ZJ, Liu ZH, Liu YM, Yao SL (2006) Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB. Br J Anaesth 97:553–558. https://doi.org/10.1093/bja/ael209
Lee HL, Lee KM, Son SJ, Hwang SH, Cho HJ (2004) Temporal expression of cytokines and their receptors mRNAs in a neuropathic pain model. Neuroreport. 15:2807–2811
Tegeder I, Niederberger E, Schmidt R, Kunz S, Guhring H, Ritzeler O, Michaelis M, Geisslinger G (2004) Specific Inhibition of IkappaB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in rats. J Neurosci 24:1637–1645. https://doi.org/10.1523/JNEUROSCI.3118-03.2004
Zhang X, Burstein R, Levy D (2012) Local action of the proinflammatory cytokines IL-1beta and IL-6 on intracranial meningeal nociceptors. Cephalalgia. 32:66–72. https://doi.org/10.1177/0333102411430848
Moreno-Sanchez D, Hernandez-Ruiz L, Ruiz FA, Docampo R (2012) Polyphosphate is a novel pro-inflammatory regulator of mast cells and is located in acidocalcisomes. J Biol Chem 287:28435–28444. https://doi.org/10.1074/jbc.M112.385823
Park JE, Barbul A (2004) Understanding the role of immune regulation in wound healing. Am J Surg 187:11S–16S. https://doi.org/10.1016/S0002-9610(03)00296-4
Schaffer M, Barbul A (1998) Lymphocyte function in wound healing and following injury. Br J Surg 85:444–460. https://doi.org/10.1046/j.1365-2168.1998.00734.x
Koyasu S, Moro K (2012) Role of innate lymphocytes in infection and inflammation. Front Immunol 3:101. https://doi.org/10.3389/fimmu.2012.00101
Mietelska-Porowska A, Wojda U (2017) T lymphocytes and inflammatory mediators in the interplay between brain and blood in Alzheimer’s disease: potential pools of new biomarkers. J Immunol Res 2017:4626540. https://doi.org/10.1155/2017/4626540
Moalem G, Xu K, Yu L (2004) T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience. 129:767–777. https://doi.org/10.1016/j.neuroscience.2004.08.035
Barcelo B, Pons J, Fuster A, Sauleda J, Noguera A, Ferrer JM, Agusti AG (2006) Intracellular cytokine profile of T lymphocytes in patients with chronic obstructive pulmonary disease. Clin Exp Immunol 145:474–479. https://doi.org/10.1111/j.1365-2249.2006.03167.x
Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C, Xu X, Yang R, Chen W et al (2011) Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-gamma and TNF-alpha. Nat Med 17:1594–1601. https://doi.org/10.1038/nm.2542
Hodge G, Nairn J, Holmes M, Reynolds PN, Hodge S (2007) Increased intracellular T helper 1 proinflammatory cytokine production in peripheral blood, bronchoalveolar lavage and intraepithelial T cells of COPD subjects. Clin Exp Immunol 150:22–29. https://doi.org/10.1111/j.1365-2249.2007.03451.x
Chung KF (2001) Cytokines in chronic obstructive pulmonary disease. Eur Respir J Suppl 34:50s–59s
Hata H, Yoshimoto T, Hayashi N, Hada T, Nakanishi K (2004) IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and Th2-cytokines and IL-8. Int Immunol 16:1733–1739. https://doi.org/10.1093/intimm/dxh174
Du JW, Xu KY, Fang LY, Qi XL (2012) Interleukin-17, produced by lymphocytes, promotes tumor growth and angiogenesis in a mouse model of breast cancer. Mol Med Rep 6:1099–1102. https://doi.org/10.3892/mmr.2012.1036
Liu J, Duan Y, Cheng X, Chen X, Xie W, Long H, Lin Z, Zhu B (2011) IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem Biophys Res Commun 407:348–354. https://doi.org/10.1016/j.bbrc.2011.03.021
Caron E, Self AJ, Hall A (2000) The GTPase Rap1 controls functional activation of macrophage integrin alphaMbeta2 by LPS and other inflammatory mediators. Curr Biol 10:974–978
Golebiewska EM, Poole AW (2015) Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev 29:153–162. https://doi.org/10.1016/j.blre.2014.10.003
Horstman LL, Jy W, Ahn YS, Zivadinov R, Maghzi AH, Etemadifar M, Steven Alexander J, Minagar A (2010) Role of platelets in neuroinflammation: a wide-angle perspective. J Neuroinflammation 7:10. https://doi.org/10.1186/1742-2094-7-10
Gould TJ, Vu TT, Swystun LL, Dwivedi DJ, Mai SH, Weitz JI, Liaw PC (2014) Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms. Arterioscler Thromb Vasc Biol 34:1977–1984. https://doi.org/10.1161/ATVBAHA.114.304114
Brem H, Balledux J, Bloom T, Kerstein MD, Hollier L (2000) Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing. Arch Surg 135:627–634
Lin H, Chen B, Sun W, Zhao W, Zhao Y, Dai J (2006) The effect of collagen-targeting platelet-derived growth factor on cellularization and vascularization of collagen scaffolds. Biomaterials 27:5708–5714. https://doi.org/10.1016/j.biomaterials.2006.07.023
Pietramaggiori G, Kaipainen A, Czeczuga JM, Wagner CT, Orgill DP (2006) Freeze-dried platelet-rich plasma shows beneficial healing properties in chronic wounds. Wound Repair Regen 14:573–580. https://doi.org/10.1111/j.1743-6109.2006.00164.x
Lederle W, Stark HJ, Skobe M, Fusenig NE, Mueller MM (2006) Platelet-derived growth factor-BB controls epithelial tumor phenotype by differential growth factor regulation in stromal cells. Am J Pathol 169:1767–1783. https://doi.org/10.2353/ajpath.2006.060120
Han G, Li F, Singh TP, Wolf P, Wang XJ (2012) The pro-inflammatory role of TGFbeta1: a paradox? Int J Biol Sci 8:228–235
Kovalsky Y, Amir R, Devor M (2009) Simulation in sensory neurons reveals a key role for delayed Na+ current in subthreshold oscillations and ectopic discharge: implications for neuropathic pain. J Neurophysiol 102:1430–1442. https://doi.org/10.1152/jn.00005.2009
Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, Castro J, Garcia-Caraballo S et al (2016) Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature. 534:494–499. https://doi.org/10.1038/nature17976
Yin R, Liu D, Chhoa M, Li CM, Luo Y, Zhang M, Lehto SG, Immke DC et al (2016) Voltage-gated sodium channel function and expression in injured and uninjured rat dorsal root ganglia neurons. Int J Neurosci 126:182–192. https://doi.org/10.3109/00207454.2015.1004172
Basbaum AI, Braz JM, Transgenic mouse models for the tracing of “pain” pathways, in Translational pain research: from mouse to man, L Kruger and AR Light, Editors. 2010: Boca Raton, FL.
Cummins TR, Sheets PL, Waxman SG (2007) The roles of sodium channels in nociception: Implications for mechanisms of pain. Pain. 131:243–257. https://doi.org/10.1016/j.pain.2007.07.026
Osteen JD, Sampson K, Iyer V, Julius D, Bosmans F (2017) Pharmacology of the Nav1.1 domain IV voltage sensor reveals coupling between inactivation gating processes. Proc Natl Acad Sci U S A 114:6836–6841. https://doi.org/10.1073/pnas.1621263114
Zhu W, Oxford GS (2011) Differential gene expression of neonatal and adult DRG neurons correlates with the differential sensitization of TRPV1 responses to nerve growth factor. Neurosci Lett 500:192–196. https://doi.org/10.1016/j.neulet.2011.06.034
Estacion M, Waxman SG (2013) The response of Na(V)1.3 sodium channels to ramp stimuli: multiple components and mechanisms. J Neurophysiol 109:306–314. https://doi.org/10.1152/jn.00438.2012
Hains BC, Klein JP, Saab CY, Craner MJ, Black JA, Waxman SG (2003) Upregulation of sodium channel Nav1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury. J Neurosci 23:8881–8892
Hains BC, Saab CY, Klein JP, Craner MJ, Waxman SG (2004) Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury. J Neurosci 24:4832–4839. https://doi.org/10.1523/JNEUROSCI.0300-04.2004
Loram LC, Harrison JA, Sloane EM, Hutchinson MR, Sholar P, Taylor FR, Berkelhammer D, Coats BD et al (2009) Enduring reversal of neuropathic pain by a single intrathecal injection of adenosine 2A receptor agonists: a novel therapy for neuropathic pain. J Neurosci 29:14015–14025. https://doi.org/10.1523/JNEUROSCI.3447-09.2009
Samad OA, Tan AM, Cheng X, Foster E, Dib-Hajj SD, Waxman SG (2013) Virus-mediated shRNA knockdown of Na(v)1.3 in rat dorsal root ganglion attenuates nerve injury-induced neuropathic pain. Mol Ther 21:49–56. https://doi.org/10.1038/mt.2012.169
Qin S, Jiang F, Zhou Y, Zhou G, Ye P, Ji Y (2017) Local knockdown of Nav1.6 relieves pain behaviors induced by BmK I. Acta Biochim Biophys Sin Shanghai 49:713–721. https://doi.org/10.1093/abbs/gmx064
Xie W, Tan ZY, Barbosa C, Strong JA, Cummins TR, Zhang JM (2016) Upregulation of the sodium channel NaVbeta4 subunit and its contributions to mechanical hypersensitivity and neuronal hyperexcitability in a rat model of radicular pain induced by local dorsal root ganglion inflammation. Pain. 157:879–891. https://doi.org/10.1097/j.pain.0000000000000453
Dib-Hajj SD, Yang Y, Black JA, Waxman SG (2013) The Na(V)1.7 sodium channel: from molecule to man. Nat Rev Neurosci 14:49–62. https://doi.org/10.1038/nrn3404
Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH, Wood JN (2004) Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci U S A 101:12706–12711. https://doi.org/10.1073/pnas.0404915101
Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C et al (2007) Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 71:311–319. https://doi.org/10.1111/j.1399-0004.2007.00790.x
Smith BJ, Cote PD, Tremblay F (2017) Contribution of Nav1.8 sodium channels to retinal function. Neuroscience. 340:279–290. https://doi.org/10.1016/j.neuroscience.2016.10.054
Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S, Zhang XF, Kort M, Carroll W et al (2007) A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci U S A 104:8520–8525. https://doi.org/10.1073/pnas.0611364104
Thakor DK, Lin A, Matsuka Y, Meyer EM, Ruangsri S, Nishimura I, Spigelman I (2009) Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy. Mol Pain 5:14. https://doi.org/10.1186/1744-8069-5-14
Faber CG, Lauria G, Merkies IS, Cheng X, Han C, Ahn HS, Persson AK, Hoeijmakers JG et al (2012) Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci U S A 109:19444–19449. https://doi.org/10.1073/pnas.1216080109
Sidaway P. (2014) Pain: Gain-of-function Nav1.9 mutations are associated with painful peripheral neuropathy. Nat Rev Neurol. 10:306. https://doi.org/10.1038/nrneurol.2014.83
Dib-Hajj SD, Black JA, Waxman SG (2015) NaV1.9: a sodium channel linked to human pain. Nat Rev Neurosci 16:511–519. https://doi.org/10.1038/nrn3977
Fang X, Djouhri L, McMullan S, Berry C, Waxman SG, Okuse K, Lawson SN (2006) Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression. J Neurosci 26:7281–7292. https://doi.org/10.1523/JNEUROSCI.1072-06.2006
Qiu F, Jiang Y, Zhang H, Liu Y, Mi W (2012) Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain. Neurosci Lett 512:61–66. https://doi.org/10.1016/j.neulet.2012.01.069
Lolignier S, Amsalem M, Maingret F, Padilla F, Gabriac M, Chapuy E, Eschalier A, Delmas P et al (2011) Nav19 channel contributes to mechanical and heat pain hypersensitivity induced by subacute and chronic inflammation. PLoS One 6(e23083). https://doi.org/10.1371/journal.pone.0023083
Amaya F, Wang H, Costigan M, Allchorne AJ, Hatcher JP, Egerton J, Stean T, Morisset V et al (2006) The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci 26:12852–12860. https://doi.org/10.1523/JNEUROSCI.4015-06.2006
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kuffler, D.P. Injury-Induced Effectors of Neuropathic Pain. Mol Neurobiol 57, 51–66 (2020). https://doi.org/10.1007/s12035-019-01756-w
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-019-01756-w