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Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog

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Abstract

Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III β-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.

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References

  • Abdulla FA, Smith PA (1999) Nerve injury increases an excitatory action of neuropeptide Y and Y2-agonists on dorsal root ganglion neurons. Neuroscience 89:43–60

    Article  PubMed  CAS  Google Scholar 

  • Ahmed M, Bjurholm A, Kreicbergs A, Schultzberg M (1993) Neuropeptide Y, tyrosine hydroxylase and vasoactive intestinal polypeptide-immunoreactive nerve fibers in the vertebral bodies, discs, dura mater, and spinal ligaments of the rat lumbar spine. Spine 18:268–273

    Article  PubMed  CAS  Google Scholar 

  • Alanentalo T, Asayesh A, Morrison H, Lorén CE, Holmberg D, Sharpe J, Ahlgren U (2007) Tomographic molecular imaging and 3D quantification within adult mouse organs. Nat Methods 4:31–33

    Article  PubMed  CAS  Google Scholar 

  • Andres KH, von Düring M, Muszynski K, Schmidt RF (1987) Nerve fibres and their terminals of the dura mater encephali of the rat. Anat Embryol 175:289–301

    Article  PubMed  CAS  Google Scholar 

  • Andres C, Meyer S, Dina OA, Levine JD, Hucho T (2010) Quantitative automated microscopy (QuAM) elucidates growth factor specific signalling in pain sensitization. Mol Pain 6:98

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Arrighi S, Bosi G, Cremonesi F, Domeneghini C (2008) Immunohistochemical study of the pre- and postnatal innervation of the dog lower urinary tract: morphological aspects at the basis of the consolidation of the micturition reflex. Vet Res Commun 32:291–304

    Article  PubMed  CAS  Google Scholar 

  • Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV (1995) Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. Eur J Neurosci 7(7):1484–1494

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bitetto WV, Thacher C (1986) A modified lateral decompressive technique for treatment of canine intervertebral disk disease. J Am Anim Hosp 23:409–413

    Google Scholar 

  • Black AP (1988) Lateral decompression in the dog: a review of 39 cases. J Small Anim Pract 29:581–588

    Article  Google Scholar 

  • Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW (1990) Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am 72:403–408

    PubMed  CAS  Google Scholar 

  • Braund KG, Taylor TK, Ghosh P, Sherwood AA (1976) Lateral spinal decompression in the dog. J Small Anim Pract 17:583–592

    Article  PubMed  CAS  Google Scholar 

  • Bridge CJ (1959) Innervation of spinal meninges and epidural structures. Anat Rec 133:553–563

    Article  PubMed  CAS  Google Scholar 

  • Brisson BA (2010) Intervertebral disc disease in dogs. Vet Clin N Am Small Anim Pract 40:829–858

    Article  Google Scholar 

  • Brumovsky P, Stanic D, Shuster S, Herzog H, Villar M, Hökfelt T (2005) Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse. J Comp Neurol 489:328–348

    Article  PubMed  CAS  Google Scholar 

  • Brumovsky P, Shi TS, Landry M, Villar MJ, Hökfelt T (2007) Neuropeptide tyrosine and pain. Trends Pharmacol Sci 28:93–102

    Article  PubMed  CAS  Google Scholar 

  • Cheng J, Ji R (2008) Intracellular signaling in primary sensory neurons and persistent pain. Neurochem Res 33:1970–1978

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Cougnon N, Hudspith MJ, Munglani R (1997) The therapeutic potential of neuropeptide Y in central nervous system disorders with special reference to pain and sympathetically maintained pain. Expert Opin Investig Drugs 6:759–769

    Article  PubMed  CAS  Google Scholar 

  • Cudia SP, Duval JM (1997) Thoracolumbar intervertebral disk disease in large, nonchondrodystrophic dogs: a retrospective study. J Am Anim Hosp Assoc 33:456–460

    PubMed  CAS  Google Scholar 

  • Day INM, Thompson RJ (2010) UCHL1 (PGP 9.5): neuronal biomarker and ubiquitin system protein. Prog Neurobiol 90:327–362

    Article  PubMed  CAS  Google Scholar 

  • Edgar MA, Ghadially JA (1976) Innervation of the lumbar spine. Clin Orthop Relat Res 115:35–41

    Google Scholar 

  • Edgar MA, Nundy S (1966) Innervation of the spinal dura mater. J Neurol Neurosurg Psychiatry 29:530–534

    Article  PubMed Central  Google Scholar 

  • Eisenberg E, McNicol ED, Carr DB (2006) Efficacy of mu-opioid agonists in the treatment of evoked neuropathic pain: systematic review of randomized controlled trials. Eur J Pain 10:667

    Article  PubMed  CAS  Google Scholar 

  • Ezaki T, Baluk P, Thurston G, La Barbara A, Woo C, McDonald DM (2001) Time course of endothelial cell proliferation and microvascular remodeling in chronic inflammation. Am J Pathol 158:2043–2055

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Forsythe WB, Ghoshal NG (1984) Innervation of the canine thoracolumbar vertebral column. Anat Rec 208:57–63

    Article  PubMed  CAS  Google Scholar 

  • Giordano A (2005) Regional-dependent increase of sympathetic innervation in rat white adipose tissue during prolonged fasting. J Histochem Cytochem 53:679–687

    Article  PubMed  CAS  Google Scholar 

  • Groen GJ, Baljet B, Drukker J (1988) The innervation of the spinal dura mater: anatomy and clinical implications. Acta Neurochir (Wien) 92:39–46

    Article  CAS  Google Scholar 

  • Halata Z (1977) The ultrastructure of the sensory nerve endings in the articular capsule of the knee joint of the domestic cat (Ruffini corpuscles and Pacinian corpuscles). J Anat 124:717–729

    PubMed  CAS  PubMed Central  Google Scholar 

  • Higuero AM, Sanchez-Ruiloba L, Doglio LE, Portillo F, Abad-Rodriguez J, Dotti CG, Iglesias T, Higuero AM, Sánchez-Ruiloba L, Doglio LE, Portillo F, Abad-Rodríguez J, Dotti CG, Iglesias T (2010) Kidins220/ARMS modulates the activity of microtubule-regulating proteins and controls neuronal polarity and development. J Biol Chem 285:1343–1357

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hökfelt T, Holets VR, Staines W, Meister B, Melander T, Schalling M, Schultzberg M, Freedman J, Björklund H, Olson L (1986) Coexistence of neuronal messengers–an overview. Prog Brain Res 68:33–70

    Article  PubMed  Google Scholar 

  • Hökfelt T, Brumovsky P, Shi T, Pedrazzini T, Villar M (2007) NPY and pain as seen from the histochemical side. Peptides 28:365–372

    Article  PubMed  Google Scholar 

  • Hoover DB, Shepherd AV, Southerland EM, Armour JA, Ardell JL (2008) Neurochemical diversity of afferent neurons that transduce sensory signals from dog ventricular myocardium. Auton Neurosci 141:38–45

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hoover DB, Isaacs ER, Jacques F, Hoard JL, Pagé P, Armour JA (2009) Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia. Neuroscience 164:1170–1179

    Article  PubMed  CAS  Google Scholar 

  • Hucho T, Levine JD (2007) Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 55:365–376

    Article  PubMed  CAS  Google Scholar 

  • Imai S, Hukuda S, Maeda T (1995) Dually innervating nociceptive networks in the rat lumbar posterior longitudinal ligaments. Spine 20:2086–2092

    Article  PubMed  CAS  Google Scholar 

  • Jackson P, Thomson VM, Thompson RJ (1985) A comparison of the evolutionary distribution of the two neuroendocrine markers, neurone-specific enolase and protein gene product 9.5. J Neurochem 45:185–190

    Article  PubMed  CAS  Google Scholar 

  • Jeffery ND (1988) Treatment of acute and chronic thoracolumbar disc disease by mini hemilaminectomy. J Small Anim Pract 29:611–616

    Article  Google Scholar 

  • Ji R, Gereau RW, Malcangio M, Strichartz GR (2009) MAP kinase and pain. Brain Res Rev 60:135–148

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Just S, Heppelmann B (2001) Neuropeptide Y changes the excitability of fine afferent units in the rat knee joint. Br J Pharmacol 132(3):703–708

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kallakuri S, Cavanaugh JM, Blagoev DC (1998) An immunohistochemical study of innervation of lumbar spinal dura and longitudinal ligaments. Spine 23:403–411

    Article  PubMed  CAS  Google Scholar 

  • Kannari K, Sato O, Maeda T, Iwanaga T, Fujita T (1991) A possible mechanism of mechanoreception in Ruffini endings in the periodontal ligament of hamster incisors. J Comp Neurol 313:368–376

    Article  PubMed  CAS  Google Scholar 

  • Keller JT, Marfurt CF (1991) Peptidergic and serotoninergic innervation of the rat dura mater. J Comp Neurol 309:515–534

    Article  PubMed  CAS  Google Scholar 

  • Kojima Y, Maeda T, Arai R, Shichikawa K (1990) Nerve supply to the posterior longitudinal ligament and the intervertebral disc of the rat vertebral column as studied by acetylcholinesterase histochemistry. I. Distribution in the lumbar region. J Anat 169:237–246

    PubMed  CAS  PubMed Central  Google Scholar 

  • Konnai Y, Honda T, Sekiguchi Y, Kikuchi S, Sugiura Y (2000) Sensory innervation of the lumbar dura mater passing through the sympathetic trunk in rats. Spine 25:776–782

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, Berger RJ, Dunsker SB, Keller JT (1996) Innervation of the spinal dura. Myth or reality? Spine 21:18–26

    Article  PubMed  CAS  Google Scholar 

  • Lundberg JM, Hökfelt T (1986) Multiple co-existence of peptides and classical transmitters in peripheral autonomic and sensory neurons—functional and pharmacological implications. Prog Brain Res 68:241–262

    Article  PubMed  CAS  Google Scholar 

  • Macias C, McKee WM, May C, Innes JF (2002) Thoracolumbar disc disease in large dogs: a study of 99 cases. J Small Anim Pract 43:439–446

    Article  PubMed  CAS  Google Scholar 

  • Messlinger K (1997) Was ist ein Nozizeptor? Schmerz 11:353–366

    Article  PubMed  CAS  Google Scholar 

  • Mongardi Fantaguzzi C, Thacker M, Chiocchetti R, Furness JB (2009) Identification of neuron types in the submucosal ganglia of the mouse ileum. Cell Tissue Res 336:179–189

    Article  PubMed  CAS  Google Scholar 

  • Nakamura S, Takahashi K, Takahashi Y, Morinaga T, Shimada Y, Moriya H (1996) Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats. Spine 21:917–924

    Article  PubMed  CAS  Google Scholar 

  • Nelson RW, Couto GC (2010) Erkrankungen des Rückenmarks. In: Nelson RW, Couto GC (eds) Innere Medizin der Kleintiere, 2nd edn. Urban & Fischer, München, pp 1106–1131

    Google Scholar 

  • Ossipov MH, Lai J, Malan TP, Porreca F (2000) Spinal and supraspinal mechanisms of neuropathic pain. Ann N Y Acad Sci 909:12–24

    Article  PubMed  CAS  Google Scholar 

  • Peleshok JC, Ribeiro-da-Silva A (2011) Delayed reinnervation by nonpeptidergic nociceptive afferents of the glabrous skin of the rat hindpaw in a neuropathic pain model. J Comp Neurol 519:49–63

    Article  PubMed  CAS  Google Scholar 

  • Perl ER (1999) Causalgia, pathological pain, and adrenergic receptors. Proc Natl Acad Sci USA 96:7664–7667

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Portmann-Lanz CB, Schoeberlein A, Portmann R, Mohr S, Rollini P, Sager R, Surbek DV (2010) Turning placenta into brain: placental mesenchymal stem cells differentiate into neurons and oligodendrocytes. Am J Obstet Gynecol 202:294.e1–294.e11

    Google Scholar 

  • Roberts WJ, Elardo SM (1985) Sympathetic activation of A-delta nociceptors. Somatosens Res 3:33–44

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko PE, Rivier J, Vale WW, Evans RM (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 304:129–135

    Article  PubMed  CAS  Google Scholar 

  • Roudenok V (2000) Changes in the expression of neuropeptide Y (NPY) during maturation of human sympathetic ganglionic neurons: correlations with tyrosine hydroxylase immunoreactivity. Ann Anat 182(6):515–519

    Article  PubMed  CAS  Google Scholar 

  • Russo D, Clavenzani P, Sorteni C, Bo Minelli L, Botti M, Gazza F, Panu R, Ragionieri L, Chiocchetti R (2013) Neurochemical features of boar lumbosacral dorsal root ganglion neurons and characterization of sensory neurons innervating the urinary bladder trigone. J Comp Neurol 521(2):342–366

    Article  PubMed  CAS  Google Scholar 

  • Saxler G, Brankamp J, Knoch M, Löer F, Hilken G, Hanesch U (2008) The density of nociceptive SP- and CGRP-immunopositive nerve fibers in the dura mater lumbalis of rats is enhanced after laminectomy, even after application of autologous fat grafts. Eur Spine J 17:1362–1372

    Article  PubMed  PubMed Central  Google Scholar 

  • Schlereth T, Birklein F (2008) The sympathetic nervous system and pain. NeuroMol Med 10:141–147

    Article  CAS  Google Scholar 

  • Schuh-Hofer S, Treede RD (2012) Definition und Pathophysiologie neuropathischer Schmerzen. Nervenheilkunde 3:115–122

    Google Scholar 

  • Sekiguchi Y, Konnai Y, Kikuchi S, Sugiura Y (1996) An anatomic study of neuropeptide immunoreactivities in the lumbar dura mater after lumbar sympathectomy. Spine 21:925–930

    Article  PubMed  CAS  Google Scholar 

  • Silva AP, Cavadas C, Grouzmann E (2002) Neuropeptide Y and its receptors as potential therapeutic drug targets. Clin Chim Acta 326:3–25

    Article  PubMed  CAS  Google Scholar 

  • Simpson ST (1992) Intervertebral disc disease. Vet Clin N Am Small Anim Pract 22:889–897

    CAS  Google Scholar 

  • Smith PA, Moran TD, Abdulla F, Tumber KK, Taylor BK (2007) Spinal mechanisms of NPY analgesia. Peptides 28:464–474

    Article  PubMed  CAS  Google Scholar 

  • Stacey BR (2005) Management of peripheral neuropathic pain. Am J Phys Med Rehabil 84:S4–S16

    PubMed  Google Scholar 

  • Stoffel MH (2011) Funktionelle Neuroanatomie für die Tiermedizin: Somatisches Nervensystem und höhere Sinne. Enke, Stuttgart, pp 122–215

    Google Scholar 

  • Suwankong N, Meij BP, Voorhout G, de Boer AH, Hazewinkel HAW (2008) Review and retrospective analysis of degenerative lumbosacral stenosis in 156 dogs treated by dorsal laminectomy. Vet Comp Orthop Traumatol 21:285–293

    PubMed  CAS  Google Scholar 

  • Tracey DJ, Cunningham JE, Romm MA (1995a) Peripheral hyperalgesia in experimental neuropathy: mediation by alpha 2-adrenoreceptors on post-ganglionic sympathetic terminals. Pain 60:317–327

    Article  PubMed  CAS  Google Scholar 

  • Tracey DJ, Romm MA, Yao NN (1995b) Peripheral hyperalgesia in experimental neuropathy: exacerbation by neuropeptide Y. Brain Res 669:245–254

    Article  PubMed  CAS  Google Scholar 

  • Treede R, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J (2008) Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 70:1630–1635

    Article  PubMed  CAS  Google Scholar 

  • Tropel P, Platet N, Platel J, Noël D, Albrieux M, Benabid A, Berger F (2006) Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells. Stem Cells 24:2868–2876

    Article  PubMed  CAS  Google Scholar 

  • Wakisaka S, Kajander KC, Bennett GJ (1991) Increased neuropeptide Y (NPY)-like immunoreactivity in rat sensory neurons following peripheral axotomy. Neurosci Lett 124:200–203

    Article  PubMed  CAS  Google Scholar 

  • Walker MW, Ewald DA, Perney TM, Miller RJ (1988) Neuropeptide Y modulates neurotransmitter release and Ca2+ currents in rat sensory neurons. J Neurosci 8:2438–2446

    PubMed  CAS  Google Scholar 

  • Wilkinson HA (1992) The failed back syndrome: the role of improper surgery in the etiology of the failed back syndrome, 2nd edn. Springer, New York

    Book  Google Scholar 

  • Willenegger S, Friess AE, Lang J, Stoffel MH (2005) Immunohistochemical demonstration of lumbar intervertebral disc innervation in the dog. Anat Histol Embryol 34:123–128

    Article  PubMed  CAS  Google Scholar 

  • Wilson PO, Barber PC, Hamid QA, Power BF, Dhillon AP, Rode J, Day IN, Thompson RJ, Polak JM (1988) The immunolocalization of protein gene product 9.5 using rabbit polyclonal and mouse monoclonal antibodies. Br J Exp Pathol 69:91–104

    PubMed  CAS  PubMed Central  Google Scholar 

  • Wong HC, Taché Y, Lloyd KC, Yang H, Sternini C, Holzer P, Walsh JH (1993) Monoclonal antibody to rat alpha-CGRP: production, characterization, and in vivo immunoneutralization activity. Hybridoma 12:93–106

    Article  PubMed  CAS  Google Scholar 

  • Woolf CJ, Costigan M (1999) Transcriptional and posttranslational plasticity and the generation of inflammatory pain. Proc Natl Acad Sci USA 96:7723–7730

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Yamada H, Honda T, Kikuchi S, Sugiura Y, 1524 (1998) Direct innervation of sensory fibers from the dorsal root ganglion of the cervical dura mater of rats. Spine 23:1524–1529 (discussion 1529–1530)

    Article  PubMed  CAS  Google Scholar 

  • Yamada H, Honda T, Yaginuma H, Kikuchi S, Sugiura Y (2001) Comparison of sensory and sympathetic innervation of the dura mater and posterior longitudinal ligament in the cervical spine after removal of the stellate ganglion. J Comp Neurol 434:86–100

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Shi T, Holmberg K, Landry M, Huang W, Xiao H, Ju G, Hökfelt T (1997) Expression and regulation of the neuropeptide Y Y2 receptor in sensory and autonomic ganglia. Proc Natl Acad Sci USA 94:729–734

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Acknowledgments

The authors express appreciation to Mrs Véronique Gaschen for her untiring laboratory work, Mr Andreas Glarner for his professional preparation work, and Mr Simon König for his excellent photographic work. Further thanks are due to Claudia Spadavecchia. Images were acquired on equipment supported by the Microscopy Imaging Center (MIC) of the University of Bern.

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The authors certify that there was no actual or potential conflict of interest in relation to this article.

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Waber-Wenger, B., Forterre, F., Kuehni-Boghenbor, K. et al. Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog. Histochem Cell Biol 142, 433–447 (2014). https://doi.org/10.1007/s00418-014-1218-x

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