Temporal mismatch between pain behaviour, skin Nerve Growth Factor and intra-epidermal nerve fibre density in trigeminal neuropathic pain

BMC Neuroscience

David Andrew¹  Peter P Robinson¹  Simon A Whawell²  Fiona M Boissonade¹  Alison R Loescher¹  Laura J Evans¹ 

[1] Oral & Maxillofacial Medicine and Surgery, University of Sheffield School of Clinical Dentistry, Claremont Crescent, Sheffield, UK;Oral & Maxillofacial Pathology, University of Sheffield School of Clinical Dentistry, Claremont Crescent, Sheffield, UK

关键词: TrkA;    hyperalgesia;    ELISA;    Neuropathic pain;    Trigeminal;   

Others  :  1122661
DOI  :  10.1186/1471-2202-15-1

 received in 2013-06-14, accepted in 2013-12-05,  发布年份 2014

【 摘 要 】

Background

The neurotrophin Nerve Growth factor (NGF) is known to influence the phenotype of mature nociceptors, for example by altering synthesis of neuropeptides, and changes in NGF levels have been implicated in the pathophysiology of chronic pain conditions such as neuropathic pain. We have tested the hypothesis that after partial nerve injury, NGF accumulates within the skin and causes ‘pro-nociceptive’ phenotypic changes in the remaining population of sensory nerve fibres, which could underpin the development of neuropathic pain.

Results

Eleven days after chronic constriction injury of the rat mental nerve the intra-epidermal nerve fibre density of the chin skin from had reduced from 11.6 ± 4.9 fibres/mm to 1.0 ± 0.4 fibres/mm; this slowly recovered to 2.4 ± 2.0 fibres/mm on day 14 and 4.0 ± 0.8 fibres/mm on day 21. Cold hyperalgesia in the ipsilateral lower lip was detectable 11 days after chronic constriction injury, although at this time skin [NGF] did not differ between sides. At 14 days post-injury, there was a significantly greater [NGF] ipsilaterally compared to contralaterally (ipsilateral = 111 ± 23 pg/mg, contralateral = 69 ± 13 pg/mg), but there was no behavioural evidence of neuropathic pain at this time-point. By 21 days post-injury, skin [NGF] was elevated bilaterally and there was a significant increase in the proportion of TrkA-positive (the high-affinity NGF receptor) intra-epidermal nerve fibres that were immunolabelled for the neuropeptide Calcitonin Gene-related peptide.

Conclusions

The temporal mismatch in behaviour, skin [NGF] and phenotypic changes in sensory nerve fibres indicate that increased [NGF] does not cause hyperalgesia after partial mental nerve injury, although it may contribute to the altered neurochemistry of cutaneous nerve fibres.

【 授权许可】

   
2014 Evans et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

Figure 11.

【 参考文献 】

• [1]Levi-Montalcini R, Angeletti PU: Essential role of the nerve growth factor in the survival and maintenance of dissociated sensory and sympathetic nerve cells in vitro. Dev Biol 1963, 7:653-659.
• [2]Goedert M, Stoeckel K, Otten U: Biological importance of retrograde axonal transport of nerve growth factor in sensory neurons. Proc Natl Acad Sci USA 1981, 78:5895-5898.
• [3]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.
• [4]Ritter AM, Lewin GR, Kremer NE, Mendell LM: Requirement for nerve growth factor in the development of myelinated nociceptors in vivo. Nature 1991, 350:500-502.
• [5]Lewin GR, Ritter AM, Mendell LM: On the role of nerve growth factor in the development of myelinated nociceptors. J Neurosci 1992, 12:1896-1905.
• [6]Bennett DL, Koltzenburg M, Priestley JV, Shelton DL, McMahon SB: Endogenous nerve growth factor regulates the sensitivity of nociceptors in the adult rat. Eur J Neurosci 1998, 10:1282-1291.
• [7]Di Marco E, Marchisio PC, Bondanza S, Franzi AT, Cancedda R, De Luca M: Growth-regulated synthesis and secretion of biologically active nerve growth factor by human keratinocytes. J Biol Chem 1991, 266:21718-22122.
• [8]Pincelli C, Sevignani C, Manfredini R, Grande A, Fantini F, Bracci-Laudiero L, Aloe L, Ferrari S, Cossarizza A, Gianetti A: Expression and function of nerve growth factor and nerve growth factor receptor on cultured keratinocytes. J Invest Dermatol 1994, 103:13-18.
• [9]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, 344:479-480.
• [10]Roggenkamp D, Falkner S, Stab F, Petersen M, Schmelz M, Neufang G: Atopic keratinocytes induce increased neurite outgrowth in a coculture model of porcine dorsal root ganglia neurons and human skin cells. J Invest Dermatol 2012, 132:1892-1900.
• [11]Petty BG, Cornblath DR, Adornato BT, Chaudry V, Flexner C, Wachsman N, Sinicropi D, Burton LE, Peroutka SJ: The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 1994, 36:244-246.
• [12]Dyck PJ, Peroutka S, Rask C, Burton E, Baker MK, Lehman KA, Gillen DA, Hokanson JL, O’Brien PC: Intradermal recombinant human nerve growth factor induces pressure allodynia and lowered heat-pain threshold in humans. Neurology 1997, 48:501-505.
• [13]Svensson P, Cairns BE, Wang K, Arendt-Neilsen L: Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia. Pain 2003, 104:241-247.
• [14]Rukweid R, Mayer A, Kluschina O, Obreja O, Schley M, Schmelz M: NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin. Pain 2010, 148:407-413.
• [15]Indo Y, Tsuruta M, Hayashida Y, Karim MA, Ohta K, Kawano T, Mitsubuchi H, Tonoki H, Awaya Y, Matsuda I: Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nat Genet 1996, 13:485-488.
• [16]Mantyh PW, Koltzenburg M, Medndell LM, Tive L, Shelton DL: Antagonism of nerve growth factor-TrkA signalling and the relief of pain. Anesthesiology 2011, 115:189-204.
• [17]Shinoda M, Asano M, Omagari D, Honda K, Hitomi S, Katagiri A, Iwata K: Nerve growth factor contribution via transient receptor potential vanilloid 1 to ectopic orofacial pain. J Neurosci 2011, 31:7145-7155.
• [18]Andreev N, Dimitirieva N, Koltzenburg M, McMahon SB: Peripheral administration of nerve growth factor in the adult rat produces a thermal hyperalgesia that requires the presence of sympathetic post-ganglionic neurones. Pain 1995, 63:109-115.
• [19]Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV: Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. Eur J Neurosci 1995, 7:1484-1494.
• [20]Lindsay RM, Harmar AJ: Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature 1989, 337:362-364.
• [21]Mamet J, Baron A, Voilley N: Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J Neurosci 2002, 22:10662-10670.
• [22]Garraway SM, Petruska JC, Mendell LM: BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs. Eur J Neurosci 2003, 18:2467-2476.
• [23]Anand P: Neurotrophic factors and their receptors in human sensory neuropathies. Prog. Brain Res 2004, 146:477-492.
• [24]Ramer MS, Bisby MA: Adrenergic innervations of rat sensory ganglia following proximal or distal painful sciatic neuropathy: distinct mechanisms revealed by anti-NGF treatment. Eur J Neurosci 1999, 11:837-846.
• [25]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.
• [26]Wild KD, Zhu D, Davis J, Bannon AW, Zhang TJ, Louis J-C: Antibodies to nerve growth factor reverse established tactile allodynia in rodent models of neuropathic pain without tolerance. J Pharmacol Exp Ther 2007, 322:282-287.
• [27]Cheng HT, Dauch JR, Hayes JM, Hong Y, Feldman EL: Nerve growth factor mediates mechanical allodynia in a mouse model of type 2 diabetes. J Neuropathol Exp Neurol 2009, 68:1229-1243.
• [28]Kim HY, Park CK, Cho IH, Jung SJ, Oh SB: Differential changes in TRPV1 expression after trigeminal sensory nerve injury. J Pain 2008, 9:280-288.
• [29]Fundin BT, Arvidsson J, Aldskogius H, Johansson O, Rice SN, Rice FL: Comprehensive immunofluorescence and lectin binding analysis of intervibrissial fur innervation of the mystacial pad of the rat. J Comp Neurol 1997, 385:185-206.
• [30]Boucher Y, Carstens MI, Sawyer CM, Zanotto KL, Merrill AW, Carstens E: Capsaicin avoidance as a measure of chemical hyperalgesia in orofacial nerve injury models. Neurosci Lett 2013, 543:37-41.
• [31]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.
• [32]Grelik C, Bennett G, Ribeiro-da-Silva A: Autonomic sprouting and changes nociceptive sensory innervation in the rat lower lip skin following chronic constriction injury. Eur J Neurosci 2005, 21:2475-2487.
• [33]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, 152:1502-1510.
• [34]Bennett GJ, Xie Y-K: A peripheral neuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33:87-107.
• [35]Lindenlaub T, Sommer C: Epidermal innervation density after partial sciatic nerve lesion and pain-related behaviour in the rat. Acta Neuropathol 2002, 104:137-143.
• [36]Seltzer Z, Dubner R, Shir Y: A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990, 43:205-218.
• [37]Holland GR, Robinson PP: The number and size of axons central and peripheral to inferior alveolar nerve injuries in the cat. J Anat 1990, 173:129-137.
• [38]Banik RK, Subieta AR, Wu C, Brennan TJ: Increased nerve growth factor after rat plantar incision contributes to guarding behaviour and heat hyperalgesia. Pain 2005, 117:68-76.
• [39]Bruno MA, Cuello AC: Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degredation by a protease cascade. Proc Natl Acad Sci USA 2006, 103:6735-6740.
• [40]Allard S, Leon WC, Pakavathkumar P, Bruno MA, Ribeiro-da-Silva R, Cuello AC: Impact of NGF maturation and degredation pathway on the cortical cholinergic system phenotype. J Neurosci 2012, 32:2002-2012.
• [41]Okragly AJ, Haak-Frendscho M: An acid-treatment method for the enhanced detection of GDNF in biological samples. Exp Neurol 1997, 145:592-596.
• [42]Vos BP, Strassman AM, Maciewicz RJ: Behavioural evidence for trigeminal neuropathic pain following chronic constriction injury to the rat’s infraorbital nerve. J Neurosci 1994, 14:2708-2723.
• [43]Dum J, Herz A: Endorphinergic modulation of neural reward systems indicated by behavioural changes. Pharmacol Biochem Behav 1984, 21:259-266.
• [44]Becker S, Gandhi W, Schweinhardt P: Cerebral interactions of pain and reward and their relevance for chronic pain. Neurosci Lett 2012, 520:182-187.
• [45]Fields HL: Understanding how opioids contribute to reward and analgesia. Reg Anesth Pain Med 2007, 32:242-246.
• [46]Nilius B, Appendino G, Owsianik G: The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch 2012, 464:425-458.
• [47]Dunham JP, Leith JL, Lumb BM, Donaldson LF: Transient receptor potential channel A1 and noxious cold responses in rat cutaneous nociceptors. Neuroscience 2010, 165:412-419.
• [48]Pezet S, McMahon SB: Neurotrophins: mediators and modulators of pain. Annu Rev Neurosci 2006, 29:507-538.
• [49]Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A: ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 2003, 112:819-829.
• [50]LaMotte RH, Thalhammer JG: Response properties of high-threshold cold receptors in the primate. Brain Res 1982, 244:279-287.
• [51]Sittl R, Lampert A, Huth T, Schuy ET, Link AS, Fleckenstein J, Alzheimerm C, Grafe P, Carr RW: Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl Acad Sci USA 2012, 109:6704-6709.
• [52]Diamond J, Foerster A, Holmes M, Coughlin M: Sensory nerves in adult rats regenerate and restore sensory function to the skin independently of endogenous NGF. J Neurosci 1992, 12:1467-1476.
• [53]Amann R, Schuligoi R, Herzeg G, Donnerer J: Intraplantar injection of nerve growth factor into the rat hindpaw: local edema and effects on thermal nociceptive threshold. Pain 1995, 64:323-329.
• [54]Harper SJ, Buchman VL, Owen D: Denervation of the skin following section of the inferior alveolar nerve leads to increased NGF accumulation without change in NGF mRNA expression. Exp Neurol 1999, 155:327-330.
• [55]Lawson SN, Crepps B, Perl ER: Calcitonin gene-related peptide immunoreactivity and afferent receptive properties of dorsal root ganglion neurones in guinea-pigs. J Physiol 2002, 540:989-1002.
• [56]Molliver DC, Radeke MJ, Feinstein SC, Snider WD: Presence or absence of TrkA protein distinguishes subsets of small sensory neurons with unique cytochemical characteristics and dorsal horn projections. J Comp Neurol 1995, 361:404-416.
• [57]Obata K, Katsura H, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukoka T, Tokunaga A, Tominaga M, Noguchi K: TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury. J Clin Invest 2005, 115:2393-2401.
• [58]Katsura H, Obata K, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Sakagami M, Noguchi K: Antisense knockdown of TRPA, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp Neurol 2006, 200:112-123.
• [59]Evans L, Andrew D, Robinson P, Boissonade F, Loescher A: Increased cutaneous NGF and CGRP-labelled trkA-positive intra-epidermal nerve fibres in rat diabetic skin. Neurosci Lett 2012, 506:59-63.
• [60]Doubleday B, Robinson PP: Nerve growth factor depletion reduces collateral sprouting of cutaneous mechanoreceptive and tooth-pulp axons in ferrets. J Physiol Lond 1994, 481:709-718.
• [61]Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Meth 1994, 53:55-63.
• [62]Chichorro JG, Zampronio AR, Souza GE, Rae GA: Orofacial cold hyperalgesia due to infraorbital nerve constriction in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs. Pain 2006, 123:64-74.
• [63]Hargreaves KM, Dubner R, Brown F, Flores C, Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988, 32:77-88.
• [64]Zettler C, Bridges DC, Zhou XF, Rush RA: Detection of increased tissue concentrations of nerve growth factor with an improved extraction method. J Neurosci Res 1996, 46:581-594.
• [65]Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, Rosenburg C, Sommer C: FENS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol 2005, 12:747-758.
• [66]Tillman DB, Treede RD, Meyer RA, Campbell JN: Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold. J Physiol (Lond) 1995, 485:753-765.
• [67]Hseih ST, Choi S, Lin WM, Chang YC, McArthur JC, Griffin JW: Epidermal denervation and its effects on keratinocytes and Langerhans cells. J Neurocytol 1996, 25:513-524.