Neurotrophic factor changes in the rat thick skin following chronic constriction injury of the sciatic nerve

Molecular Pain

Alfredo Ribeiro-da-Silva¹  Jennifer C Peleshok² 

[1] Departments of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada;Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec H3A 2B2, Canada

关键词: Schwann cell;    p75;    peptidergic;    mast cell;    chronic constriction injury;    nerve growth factor;    sciatic nerve;   

Others  :  865580
DOI  :  10.1186/1744-8069-8-1

 received in 2011-08-30, accepted in 2012-01-10,  发布年份 2012

【 摘 要 】

Background

Cutaneous peripheral neuropathies have been associated with changes of the sensory fiber innervation in the dermis and epidermis. These changes are mediated in part by the increase in local expression of trophic factors. Increase in target tissue nerve growth factor has been implicated in the promotion of peptidergic afferent and sympathetic efferent sprouting following nerve injury. The primary source of nerve growth factor is cells found in the target tissue, namely the skin. Recent evidence regarding the release and extracellular maturation of nerve growth factor indicate that it is produced in its precursor form and matured in the extracellular space. It is our hypothesis that the precursor form of nerve growth factor should be detectable in those cell types producing it. To date, limitations in available immunohistochemical tools have restricted efforts in obtaining an accurate distribution of nerve growth factor in the skin of naïve animals and those with neuropathic pain lesions. It is the objective of this study to delineate the distribution of the precursor form of nerve growth factor to those cell types expressing it, as well as to describe its distribution with respect to those nerve fibers responsive to it.

Results

We observed a decrease in peptidergic fiber innervation at 1 week after the application of a chronic constriction injury (CCI) to the sciatic nerve, followed by a recovery, correlating with TrkA protein levels. ProNGF expression in CCI animals was significantly higher than in sham-operated controls from 1-4 weeks post-CCI. ProNGF immunoreactivity was increased in mast cells at 1 week post-CCI and, at later time points, in keratinocytes. P75 expression within the dermis and epidermis was significantly higher in CCI-operated animals than in controls and these changes were localized to neuronal and non-neuronal cell populations using specific markers for each.

Conclusions

We describe proNGF expression by non-neuronal cells over time after nerve injury as well as the association of NGF-responsive fibers to proNGF-expressing target tissues. ProNGF expression increases following nerve injury in those cell types previously suggested to express it.

【 授权许可】

   
2012 Peleshok and Ribeiro-da-Silva; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Holland DR, Cousens LS, Meng W, Matthews BW: Nerve growth factor in different crystal forms displays structural flexibility and reveals zinc binding sites. J Mol Biol 1994, 239:385-400.
• [2]Goedert M, Otten U, Hunt SP, Bond A, Chapman D, Schlumpf M, Lichtensteiger W: Biochemical and anatomical effects of antibodies against nerve growth factor on developing rat sensory ganglia. Proc Natl Acad Sci USA 1984, 81:1580-1584.
• [3]Goedert M, Stoeckel K, Otten U: Biological importance of the retrograde axonal transport of nerve growth factor in sensory neurons. Proc Natl Acad Sci USA 1981, 78:5895-5898.
• [4]Levi-Montalcini R, Angeletti PU: Essential role of the nerve growth factor on the survival and maintenance of dissociated sensory and sympathetic embryonic nerve cells in vitro. Dev Biol 1963, 7:653-659.
• [5]Albers KM, Wright DE, Davis BM: Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system. J Neurosci 1994, 14:1422-1432.
• [6]Davis BM, Fundin BT, Albers KM, Goodness TP, Cronk KM, Rice FL: Overexpression of nerve growth factor in skin causes preferential increases among innervation to specific sensory targets. J Comp Neurol 1997, 387:489-506.
• [7]Davis BM, Lewin GR, Mendell LM, Jones ME, Albers KM: Altered expression of nerve growth factor in the skin of transgenic mice leads to changes in response to mechanical stimuli. Neuroscience 1993, 56:789-792.
• [8]Yen LD, Bennett GJ, Ribeiro-da-Silva A: Sympathetic sprouting and changes in nociceptive sensory innervation in the glabrous skin of the rat hind paw following partial peripheral nerve injury. J Comp Neurol 2006, 495:679-690.
• [9]Grelik C, Bennett GJ, Ribeiro-da-Silva A: Autonomic fiber sprouting and changes in nociceptive sensory innervation in the rat lower lip skin following chronic constriction injury. Eur J Neurosci 2005, 21:2475-2487.
• [10]Grelik C, Allard S, Ribeiro-da-Silva A: Changes in nociceptive sensory innervation in the epidermis of the rat lower lip skin in a model of neuropathic pain. Neurosci Lett 2005, 389:140-145.
• [11]Ruocco I, Cuello AC, Ribeiro-da-Silva A: Peripheral nerve injury leads to the establishment of a novel pattern of sympathetic fibre innervation in the rat skin. J Comp Neurol 2000, 422:287-296.
• [12]Peleshok JC, Ribeiro-da-Silva A: Delayed reinnervation by nonpeptidergic nociceptive afferents of the glabrous skin of the rat hindpaw in a neuropathic pain model. J Comp Neurol 2011, 519:49-63.
• [13]Lumsden AG, Davies AM: Earliest sensory nerve fibres are guided to peripheral targets by attractants other than nerve growth factor. Nature 1983, 306:786-788.
• [14]Verge VMK, Richardson PM, Benoit R, Riopelle RJ: Histochemical characterization of sensory neurons with high-affinity receptors for nerve growth factor. J Neurocytol 1989, 18:583-591.
• [15]Verge VMK, Riopelle RJ, Richardson PM: Nerve growth factor receptors on normal and injured sensory neurons. J Neurosci 1989, 9:914-922.
• [16]Ribeiro-da-Silva A, Kenigsberg RL, Cuello AC: Light and electron microscopic distribution of nerve growth factor receptor-like immunoreactivity in the skin of the rat lower lip. Neuroscience 1991, 43:631-646.
• [17]Chao MV: Neurotrophins and their receptors: a convergence point for many signalling pathways. Nature Rev Neurosci 2003, 4:299-309.
• [18]Reichardt LF: Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 2006, 361:1545-1564.
• [19]Barker PA: High affinity not in the vicinity? Neuron 2007, 53:1-4.
• [20]Wehrman T, He X, Raab B, Dukipatti A, Blau H, Garcia KC: Structural and mechanistic insights into nerve growth factor interactions with the TrkA and p75 receptors. Neuron 2007, 53:25-38.
• [21]Sutter A, Riopelle LF, Harris-Harrik RM, Shooter EM: Nerve growth factor receptors: characterization of two distinct classes of binding sites on chick embryo sensory gnglia cells. J Biol Chem 1979, 254:5972-5982.
• [22]Nicol GD, Vasko MR: Unraveling the Story of NGF-mediated Sensitization of Nociceptive Sensory Neurons: ON or OFF the Trks? Mol Interventions 2007, 7:26-41.
• [23]Heumann R, Lindholm D, Bandtlow C, Meyer M, Radeke MJ, Misko TP, Shooter E, Thoenen H: Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc Natl Acad Sci USA 1987, 84:8735-8739.
• [24]Heumann R, Korsching S, Bandtlow C, Thoenen H: Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection. J Cell Biol 1987, 104:1623-1631.
• [25]Aloe L, Levi-Montalcini R: Mast cells increase in tissues of neonatal rats injected with the nerve growth factor. Brain Res 1977, 133:358-366.
• [26]Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L, Levi-Montalcini R: Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci USA 1994, 91:3739-3743.
• [27]English KB, Harper S, Stayner N, Wang ZM, Davies AM: Localization of nerve growth factor (NGF) and low-affinity NGF receptors in touch domes and quantification of NGF mRNA in keratinocytes of adult rats. J Comp Neurol 1994, 344:470-480.
• [28]Spitsbergen JM, Stewart JS, Tuttle JB: Altered regulation of nerve growth factor secretion by cultured VSMCs from hypertensive rats. Am J Physiol 1995, 269:H621-628.
• [29]Masoudi R, Ioannou MS, Coughlin MD, Pagadala P, Neet KE, Clewes O, Allen SJ, Dawbarn D, Fahnestock M: Biological Activity of Nerve Growth Factor Precursor Is Dependent upon Relative Levels of Its Receptors. J Biol Chem 2009, 284:18424-18433.
• [30]Feng D, Kim T, Ozkan E, Light M, Torkin R, Teng KK, Hempstead BL, Garcia KC: Molecular and structural insight into proNGF engagement of p75NTR and sortilin. J Mol Biol 2010, 396:967-984.
• [31]Kiss M, Dallos A, Kormos B, Santha P, Dobozy A, Husz S, Kemeny L: Sortilin Is Expressed in Cultured Human Keratinocytes and Is Regulated by Cutaneous Neuropeptides. J Invest Dermatol 2010, 130:2553-2560.
• [32]Inoue K, Koizumi S, Fuziwara S, Denda S, Denda M: Functional vanilloid receptors in cultured normal human epidermal keratinocytes. Biochem Biophys Res Commun 2002, 291:124-129.
• [33]Zhao P, Barr TP, Hou Q, Dib-Hajj SD, Black JA, Albrecht PJ, Petersen K, Eisenberg E, Wymer JP, Rice FL, Waxman SG: Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain. Pain 2008, 139:90-105.
• [34]Bruno MA, Cuello AC: Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade. Proceedings of the National Academy of Sciences 2006, 103:6735-6740.
• [35]Lee R, Kermani P, Teng KK, Hempstead BL: Regulation of Cell Survival by Secreted Proneurotrophins. Science 2001, 294:1945-1948.
• [36]Wu C, Boustany L, Liang H, Brennan TJ: Nerve growth factor expression after plantar incision in the rat. Anesthesiology 2007, 107:128-135.
• [37]Ramer MS, French GD, Bisby MA: Wallerian degeneration is required for both neuropathic pain and sympathetic sprouting into the DRG. Pain 1997, 72:71-78.
• [38]Scholz J, Woolf CJ: The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 2007, 10:1361-1368.
• [39]Hattori A, Tanaka E, Murase K, Ishida N, Chatani Y, Tsujimoto M, Hayashi K, Kohno M: Tumor necrosis factor stimulates the synthesis and secretion of biologically active nerve growth factor in non-neuronal cells. J Biol Chem 1993, 268:2577-2582.
• [40]Lindholm D, Heumann R, Meyer M, Thoenen H: Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve. Nature 1987, 330:658-659.
• [41]Bergsteinsdottir K, Kingston A, Mirsky R, Jessen KR: Rat Schwann cells produce interleukin-1. J Neuroimmunol 1991, 34:15-23.
• [42]Bechtel MJ, Reinartz J, Rox JM, Inndorf S, Schaefer BM, Kramer MD: Upregulation of cell-surface-associated plasminogen activation in cultured keratinocytes by interleukin-1 beta and tumor necrosis factor-alpha. Exp Cell Res 1996, 223:395-404.
• [43]Han YP, Downey S, Garner WL: Interleukin-1alpha-induced proteolytic activation of metalloproteinase-9 by human skin. Surgery 2005, 138:932-939.
• [44]Zhou L, Yan C, Gieling RG, Kida Y, Garner W, Li W, Han YP: Tumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated kinase-1. BMC Immunol 2009, 10:15. BioMed Central Full Text
• [45]Bandtlow CE, Heumann R, Schwab ME, Thoenen H: Cellular localization of nerve growth factor synthesis by in situ hybridization. EMBO J 1987, 6:891-899.
• [46]Heumann R, Korsching S, Scott J, Thoenen H: Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues. EMBO J 1984, 3:3183-3189.
• [47]Pezet S, Marchand F, D'Mello R, Grist J, Clark AK, Malcangio M, Dickenson AH, Williams RJ, McMahon SB: Phosphatidylinositol 3-Kinase Is a Key Mediator of Central Sensitization in Painful Inflammatory Conditions. J Neurosci 2008, 28:4261-4270.
• [48]Pezet S, McMahon SB: Neurotrophins: Mediators and Modulators of Pain. Annu Rev Neurosci 2006, 29:507-538.
• [49]Pezet S, Onteniente B, Jullien J, Junier M, Grannec G, Rudkin B: Differential regulation of NGF receptors in primary sensory neurons by adjuvant-induced arthritis in the rat. Pain 2001, 90:113-125.
• [50]Ro LS, Chen ST, Tang LM, Jacobs JM: Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve. Pain 1999, 79:265-274.
• [51]Ugolini G, Marinelli S, Covaceuszach S, Cattaneo A, Pavone F: The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain. Proceedings of the National Academy of Sciences 2007, 104:2985-2990.
• [52]Taniuchi M, Clark HB, Johnson EM Jr: Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci USA 1986, 83:4094-4098.
• [53]Taniuchi M, Clark HB, Schweitzer JB, Johnson EM Jr: Expression of nerve growth factor receptors by Schwann cells of axotomized peripheral nerves: ultrastructural location, suppression by axonal contact, and binding properties. J Neurosci 1988, 8:664-681.
• [54]Ramer M, Bisby M: Reduced sympathetic sprouting occurs in dorsal root ganglia after axotomy in mice lacking low-affinity neurotrophin receptor. Neurosci Lett 1997, 228:9-12.
• [55]Hefti FF, Rosenthal A, Walicke PA, Wyatt S, Vergara G, Shelton DL, Davies AM: Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol Sci 2006, 27:85-91.
• [56]Herzberg U, Eliav E, Dorsey JM, Gracely RH, Kopin IJ: NGF involvement in pain induced by chronic constriction injury of the rat sciatic nerve. Neuroreport 1997, 8:1613-1618.
• [57]Hoheisel U, Unger T, Mense S: Sensitization of rat dorsal horn neurons by NGF-induced subthreshold potentials and low-frequency activation. A study employing intracellular recordings in vivo. Brain Res 2007, 1169:34-43.
• [58]Ramer MS, Kawaja MD, Henderson JT, Roder JC, Bisby MA: Glial overexpression of NGF enhances neuropathic pain and adrenergic sprouting into DRG following chronic sciatic constriction in mice. Neurosci Lett 1998, 251:53-56.
• [59]Gonzalez-Martinez T, Perez-Pinera P, Diaz-Esnal B, Vega JA: S-100 proteins in the human peripheral nervous system. Microsc Res Tech 2003, 60:633-638.
• [60]Mearow KM, Kril Y, Diamond J: Increased NGF mRNA expression in denervated rat skin. Neuroreport 1993, 4:351-354.
• [61]Lindholm D, Heumann R, Hengerer B, Thoenen H: Interleukin 1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts. J Biol Chem 1988, 263:16348-16351.
• [62]Johnson EM, Taniuchi M, DiStefano PS: Expression and possible function of nerve growth factor receptors on Schwann cells. Trends Neurosci 1988, 11:299-304.
• [63]Zhou XF, Rush RA, McLachlan EM: Differential expression of the p75 nerve growth factor receptor in glia and neurons of the rat dorsal root ganglia after peripheral nerve transection. J Neurosci 1996, 16:2901-2911.
• [64]Ma W, Bisby MA: Calcitonin gene-related peptide, substance P and protein gene product 9.5 immunoreactive axonal fibers in the rat footpad skin following partial sciatic nerve injuries. J Neurocytol 2000, 29:249-262.
• [65]Taylor AM, Ribeiro-da-Silva A: GDNF levels in the lower lip skin in a rat model of trigeminal neuropathic pain: Implications for nonpeptidergic fiber reinnervation and parasympathetic sprouting. Pain 2011.
• [66]Scott AL, Ramer MS: Schwann cell p75NTR prevents spontaneous sensory reinnervation of the adult spinal cord. Brain 2010, 133:421-432.
• [67]Coggeshall RE, Dougherty PM, Pover CM, Carlton SM: Is large myelinated fiber loss associated with hyperalgesia in a model of experimental peripheral neuropathy in the rat. Pain 1993, 52:233-242.
• [68]Basbaum AI, Gautron M, Jazat F, Mayes M, Guilbaud G: The spectrum of fiber loss in a model of neuropathic pain in the rat: An electron microscopic study. Pain 1991, 47:359-367.
• [69]Allard S, Leon WC, Pakavathkumar P, Bruno MA, Ribeiro-da-Silva A, Cuello AC: Impact of the NGF maturation and degradation pathway on the corticalcholinergic system phenotype. The Journal of Neuroscience 2011, in press.
• [70]Irnich D, Burgstahler R, Bostock H, Grafe P: ATP affects both axons and Schwann cells of unmyelinated C fibres. Pain 2001, 92:343-350.
• [71]Baker MD: Electrophysiology of mammalian Schwann cells. Prog Biophys Mol Biol 2002, 78:83-103.
• [72]Levi-Montalcini R, Booker B: Excessive growth of the sympathetic ganglia evoked by a protein isolated from mouse salivary glands. Proc Natl Acad Sci USA 1960, 46:373-384.
• [73]Ruocco I, Cuello AC, Parent A, Ribeiro-da-Silva A: Skin blood vessels are simultaneously innervated by sensory, sympathetic, and parasympathetic fibers. J Comp Neurol 2002, 448:323-336.
• [74]Bennett GJ, Xie YK: A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33:87-107.
• [75]Fundin BT, Pfaller K, Rice FL: Different distributions of the sensory and autonomic innervation among the microvasculature of the rat mystacial pad. J Comp Neurol 1997, 389:545-568.
• [76]Rice FL, Fundin BT, Arvidsson J, Aldskogius H, Johansson O: Comprehensive immunofluorescence and lectin binding analysis of vibrissal follicle sinus complex innervation in the mystacial pad of the rat. J Comp Neurol 1997, 385:149-184.
• [77]Paré M, Albrecht PJ, Noto CJ, Bodkin NL, Pittenger GL, Schreyer DJ, Tigno XT, Hansen BC, Rice FL: Differential hypertrophy and atrophy among all types of cutaneous innervation in the glabrous skin of the monkey hand during aging and naturally occurring type 2 diabetes. J Comp Neurol 2007, 501:543-567.
• [78]Mazzoni I, Jaffe E, Cuello A: Production and immunocytochemical application of a highly sensitive and specific monoclonal antibody against rat dopamine-beta-hydroxylase. Histochemistry 1991, 96:45-50.
• [79]Yu WM, Chen ZL, North AJ, Strickland S: Laminin is required for Schwann cell morphogenesis. J Cell Sci 2009, 122:929-936.
• [80]Taniuchi M, Johnson EM Jr: Characterization of the binding properties and retrograde axonal transport of a monoclonal antibody directed against the nerve growth factor receptor. J Cell Biol 1985, 101:1100-1106.
• [81]Doran JF, Jackson P, Kynoch PAM, Thompson RJ: Isolation of PGP 9.5, a New Human Neurone-Specific Protein Detected by High-Resolution Two-Dimensional Electrophoresis. J Neurochem 1983, 40:1542-1547.
• [82]Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J: PGP 9.5--a new marker for vertebrate neurons and neuroendocrine cells. Brain Res 1983, 278:224-228.