Skip to main content
SpringerLink
Log in

Animal Models of Neuropathic Pain Due to Nerve Injury

  • Protocol
  • First Online:
Stimulation and Inhibition of Neurons

Part of the book series: Neuromethods ((NM,volume 78))

Abstract

Chronic neuropathic pain is a frequent outcome of nervous system injury affecting the somatosensory system, and its pathobiology is dependent on activation and disinhibition of nociceptive neurons. It is characterised by spontaneous pain, dysaesthesia/paraesthesia as well as hypersensitivity to normally non-painful (allodynia) and painful (hyperalgesia) mechanical and thermal stimuli. Behavioural disabilities, such as depression, insomnia and alterations in social behaviours, are also co-morbid with changes in sensation. To investigate the mechanisms which result in neuropathic pain, animal models of neuropathy were developed by performing standardised, reproducible nerve injuries via surgical manipulation of a peripheral nerve. Here, we present four commonly used models in laboratory rodents for the study of neuropathic pain: (1) chronic constriction injury of the sciatic nerve, (2) partial sciatic nerve ligation, (3) L5 and/or L6 spinal nerve ligation and (4) the spared nerve injury, where two of the three terminal sciatic branches are cut. Rodents which have undergone any one of these procedures routinely display increased pain responses, such as allodynia and hyperalgesia of the hindpaw, lasting up to several months. Investigators should be aware however that such animal models suffer from several limitations including inconsistency in predicting the clinical success of novel therapeutics, poor correlation with clinical neuropathic pain in terms of prevalent symptoms and timescale and the need to assess operant/affective behavioural responses in addition to reflexive withdrawals from mechanical and thermal stimuli. Despite these limitations, animal models of peripheral nerve injury combined with testing of pain hypersensitivity remain necessary to investigate the pathophysiological mechanisms and identify novel therapeutic agents to treat chronic neuropathic pain.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Blyth FM, March LM, Brnabic AJ, Jorm LR, Williamson M, Cousins MJ (2001) Chronic pain in Australia: a prevalence study. Pain 89(2–3):127–134

    Article  PubMed  CAS  Google Scholar 

  2. Treede RD, 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(18):1630–1635

    Article  PubMed  CAS  Google Scholar 

  3. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C (2008) Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 136(3):380–387

    Article  PubMed  Google Scholar 

  4. Toth C, Lander J, Wiebe S (2009) The prevalence and impact of chronic pain with neuropathic pain symptoms in the general population. Pain Med 10(5):918–929

    Article  PubMed  Google Scholar 

  5. Kehlet H, Jensen TS, Woolf CJ (2006) Persistent postsurgical pain: risk factors and prevention. Lancet 367(9522):1618–1625

    Article  PubMed  Google Scholar 

  6. Wall PD, Gutnick M (1974) Properties of afferent nerve impulses originating from a neuroma. Nature 248(5451):740–743

    Article  PubMed  CAS  Google Scholar 

  7. Wall PD, Devor M, Inbal R, Scadding JW, Schonfeld D, Seltzer Z, Tomkiewicz MM (1979) Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa. Pain 7(2):103–111

    Article  PubMed  CAS  Google Scholar 

  8. Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33(1):87–107

    Article  PubMed  CAS  Google Scholar 

  9. Ze S, Dubner R, Shir Y (1990) A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43(2):205–218

    Article  Google Scholar 

  10. Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50(3):355–363

    Article  PubMed  CAS  Google Scholar 

  11. Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87(2):149–158

    Article  PubMed  CAS  Google Scholar 

  12. Kim KJ, Yoon YW, Chung JM (1997) Comparison of three rodent neuropathic pain models. Exp Brain Res 113(2):200–206

    Article  PubMed  CAS  Google Scholar 

  13. Dowdall T, Robinson I, Meert TF (2005) Comparison of five different rat models of peripheral nerve injury. Pharmacol Biochem Behav 80(1):93–108

    Article  PubMed  Google Scholar 

  14. Campbell JN, Meyer RA (2006) Mechanisms of neuropathic pain. Neuron 52(1):77–92

    Article  PubMed  CAS  Google Scholar 

  15. Costigan M, Scholz J, Woolf CJ (2009) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 32:1–32

    Article  PubMed  CAS  Google Scholar 

  16. Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10(9):895–926

    Article  PubMed  Google Scholar 

  17. Bennett GJ, Chung JM, Honore M, Seltzer Z (2003) Models of neuropathic pain in the rat. Current protocols in neuroscience 9.14.1–9.14.16 Copyright © 2003 by John Wiley & Sons, Inc. Wiley, New York

    Google Scholar 

  18. Attal N, Jazat F, Kayser V, Guilbaud G (1990) Further evidence for ‘pain-related’ behaviours in a model of unilateral peripheral mononeuropathy. Pain 41(2):235–251

    Article  PubMed  CAS  Google Scholar 

  19. Bennett GJ (1993) An animal model of neuropathic pain: a review. Muscle Nerve 16(10):1040–1048

    Article  PubMed  CAS  Google Scholar 

  20. Kupers RC, Nuytten D, De Castro-Costa M, Gybels JM (1992) A time course analysis of the changes in spontaneous and evoked behaviour in a rat model of neuropathic pain. Pain 50(1):101–111

    Article  PubMed  CAS  Google Scholar 

  21. Monassi CR, Bandler R, Keay KA (2003) A subpopulation of rats show social and sleep-waking changes typical of chronic neuropathic pain following peripheral nerve injury. Eur J Neurosci 17(9):1907–1920

    Article  PubMed  Google Scholar 

  22. Paulson PE, Casey KL, Morrow TJ (2002) Long-term changes in behavior and regional cerebral blood flow associated with painful peripheral mononeuropathy in the rat. Pain 95(1–2):31–40

    Article  PubMed  Google Scholar 

  23. Austin PJ, Beyer K, Bembrick AL, Keay KA (2010) Peripheral nerve injury differentially regulates dopaminergic pathways in the nucleus accumbens of rats with either ‘pain alone’ or ‘pain and disability’. Neuroscience 171(1):329–343

    Article  PubMed  CAS  Google Scholar 

  24. Keay KA, Monassi CR, Levison DB, Bandler R (2004) Peripheral nerve injury evokes disabilities and sensory dysfunction in a subpopulation of rats: a closer model to human chronic neuropathic pain? Neurosci Lett 361(1–3):188–191

    Article  PubMed  CAS  Google Scholar 

  25. Jesse C, Wilhelm E, Nogueira C (2010) Depression-like behavior and mechanical allodynia are reduced by bis selenide treatment in mice with chronic constriction injury: a comparison with fluoxetine, amitriptyline, and bupropion. Psychopharmacology 212(4):513–522

    Article  PubMed  CAS  Google Scholar 

  26. Roeska K, Doods H, Arndt K, Treede RD, Ceci A (2008) Anxiety-like behaviour in rats with mononeuropathy is reduced by the analgesic drugs morphine and gabapentin. Pain 139(2):349–357

    Article  PubMed  CAS  Google Scholar 

  27. Hu B, Doods H, Treede R-D, Ceci A (2009) Depression-like behaviour in rats with mononeuropathy is reduced by the CB2-selective agonist GW405833. Pain 143(3):206–212

    Article  PubMed  CAS  Google Scholar 

  28. Kontinen VK, Kauppila T, Paananen S, Pertovaara A, Kalso E (1999) Behavioural measures of depression and anxiety in rats with spinal nerve ligation-induced neuropathy. Pain 80(1–2):341–346

    Article  PubMed  CAS  Google Scholar 

  29. Urban R, Scherrer G, Goulding EH, Tecott LH, Basbaum AI (2011) Behavioral indices of ongoing pain are largely unchanged in male mice with tissue or nerve injury-induced mechanical hypersensitivity. Pain 152(5):990–1000

    Article  PubMed  Google Scholar 

  30. Maves TJ, Pechman PS, Gebhart GF, Meller ST (1993) Possible chemical contribution from chromic gut sutures produces disorders of pain sensation like those seen in man. Pain 54(1):57–69

    Article  PubMed  CAS  Google Scholar 

  31. Xu J, Pollock CH, Kajander KC (1996) Chromic gut suture reduces calcitonin-gene-related peptide and substance P levels in the spinal cord following chronic constriction injury in the rat. Pain 64(3):503–509

    Article  PubMed  CAS  Google Scholar 

  32. Sommer C, Lindenlaub T, Teuteberg P, Schäfers M, Hartung T, Toyka KV (2001) Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy. Brain Res 913(1):86–89

    Article  PubMed  CAS  Google Scholar 

  33. Walczak J-S, Beaulieu P (2006) Comparison of three models of neuropathic pain in mice using a new method to assess cold allodynia: the double plate technique. Neurosci Lett 399(3):240–244

    Article  PubMed  CAS  Google Scholar 

  34. Vos BP, Strassman AM, Maciewicz RJ (1994) Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury to the rat’s infraorbital nerve. J Neurosci 14(5 Pt 1):2708–2723

    PubMed  CAS  Google Scholar 

  35. Imamura Y, Kawamoto H, Nakanishi O (1997) Characterization of heat-hyperalgesia in an experimental trigeminal neuropathy in rats. Exp Brain Res 116(1):97–103

    Article  PubMed  CAS  Google Scholar 

  36. Grace PM, Hutchinson MR, Manavis J, Somogyi AA, Rolan PE (2010) A novel animal model of graded neuropathic pain: utility to investigate mechanisms of population heterogeneity. J Neurosci Methods 193(1):47–53

    Article  PubMed  Google Scholar 

  37. Hasnie FS, Wallace VC, Hefner K, Holmes A, Rice AS (2007) Mechanical and cold hypersensitivity in nerve-injured C57BL/6J mice is not associated with fear-avoidance- and depression-related behaviour. Br J Anaesth 98(6):816–822

    Article  PubMed  CAS  Google Scholar 

  38. Malmberg AB, Basbaum AI (1998) Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain 76(1–2):215–222

    Article  PubMed  CAS  Google Scholar 

  39. Norman GJ, Karelina K, Zhang N, Walton JC, Morris JS, Devries AC (2010) Stress and IL-1beta contribute to the development of depressive-like behavior following peripheral nerve injury. Mol Psychiatry 15(4):404–414

    Article  PubMed  CAS  Google Scholar 

  40. Leite-Almeida H, Almeida-Torres L, Mesquita AR, Pertovaara A, Sousa N, Cerqueira JJ, Almeida A (2009) The impact of age on emotional and cognitive behaviours triggered by experimental neuropathy in rats. Pain 144(1–2):57–65

    Article  PubMed  Google Scholar 

  41. Pertin M, Allchorne AJ, Beggah AT, Woolf CJ, Decosterd I (2007) Delayed sympathetic dependence in the spared nerve injury (SNI) model of neuropathic pain. Mol Pain 3:21

    Article  PubMed  Google Scholar 

  42. Bourquin AF, Suveges M, Pertin M, Gilliard N, Sardy S, Davison AC, Spahn DR, Decosterd I (2006) Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse. Pain 122(1–2):14.e1–14

    Article  Google Scholar 

  43. Shields SD, Eckert WA, Basbaum AI (2003) Spared nerve injury model of neuropathic pain in the mouse: a behavioral and anatomic analysis. J Pain 4(8):465–470

    Article  PubMed  Google Scholar 

  44. Lee BH, Won R, Baik EJ, Lee SH, Moon CH (2000) An animal model of neuropathic pain employing injury to the sciatic nerve branches. Neuroreport 11(4):657–661

    Article  PubMed  CAS  Google Scholar 

  45. Han DW, Kweon TD, Kim KJ, Lee JS, Chang CH, Lee YW (2006) Does the tibial and sural nerve transection model represent sympathetically independent pain? Yonsei Med J 47(6):847–851

    Article  PubMed  Google Scholar 

  46. Vadakkan KI, Jia YH, Zhuo M (2005) A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice. J Pain 6(11):747–756

    Article  PubMed  Google Scholar 

  47. Simkins MD, Shadiack AM, Burns CA, Molino LJ, Amaratunga D, Hall J, Rogers KE, Clark LP (1998) Evaluation of post-operative analgesics in a model of neuropathic pain. J Am Assoc Lab Anim Sci 37(6):61–63

    Google Scholar 

  48. Choi Y, Yoon YW, Na HS, Kim SH, Chung JM (1994) Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain 59(3):369–376

    Article  PubMed  CAS  Google Scholar 

  49. Suzuki T, Amata M, Sakaue G, Nishimura S, Inoue T, Shibata M, Mashimo T (2007) Experimental neuropathy in mice is associated with delayed behavioral changes related to anxiety and depression. Anesth Analg 104(6):1570–1577

    Article  PubMed  Google Scholar 

  50. Kim SH, Na HS, Sheen K, Chung JM (1993) Effects of sympathectomy on a rat model of peripheral neuropathy. Pain 55(1):85–92

    Article  PubMed  CAS  Google Scholar 

  51. LaBuda CJ, Fuchs PN (2000) A behavioral test paradigm to measure the aversive quality of inflammatory and neuropathic pain in rats. Exp Neurol 163(2):490–494

    Article  PubMed  CAS  Google Scholar 

  52. LaBuda CJ, Little PJ (2005) Pharmacological evaluation of the selective spinal nerve ligation model of neuropathic pain in the rat. J Neurosci Methods 144(2):175–181

    Article  PubMed  CAS  Google Scholar 

  53. LaGraize SC, Borzan J, Fuchs PN (2003) Decreased L5 spinal nerve ligation nociceptive behavior following L4 spinal nerve transection. Brain Res 990(1–2):227–230

    Article  PubMed  CAS  Google Scholar 

  54. Cao L, DeLeo JA (2008) CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur J Immunol 38(2):448–458

    Article  PubMed  CAS  Google Scholar 

  55. Tanga FY, Nutile-McMenemy N, DeLeo JA (2005) The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA 102(16):5856–5861

    Article  PubMed  CAS  Google Scholar 

  56. DeLeo JA, Rutkowski MD (2000) Gender differences in rat neuropathic pain sensitivity is dependent on strain. Neurosci Lett 282(3):197–199

    Article  PubMed  CAS  Google Scholar 

  57. Tall JM, Stuesse SL, Cruce WL, Crisp T (2001) Gender and the behavioral manifestations of neuropathic pain. Pharmacol Biochem Behav 68(1):99–104

    Article  PubMed  CAS  Google Scholar 

  58. Mogil JS, Davis KD, Derbyshire SW (2010) The necessity of animal models in pain research. Pain 151(1):12–17

    Article  PubMed  Google Scholar 

  59. Howard RF, Walker SM, Mota PM, Fitzgerald M (2005) The ontogeny of neuropathic pain: postnatal onset of mechanical allodynia in rat spared nerve injury (SNI) and chronic constriction injury (CCI) models. Pain 115(3):382–389

    Article  PubMed  Google Scholar 

  60. Chung JM, Choi Y, Yoon YW, Na HS (1995) Effects of age on behavioral signs of neuropathic pain in an experimental rat model. Neurosci Lett 183(1–2):54–57

    Article  PubMed  CAS  Google Scholar 

  61. Crisp T, Giles JR, Cruce WL, McBurney DL, Stuesse SL (2003) The effects of aging on thermal hyperalgesia and tactile-evoked allodynia using two models of peripheral mononeuropathy in the rat. Neurosci Lett 339(2):103–106

    Article  PubMed  CAS  Google Scholar 

  62. Kim YI, Na HS, Yoon YW, Nahm SH, Ko KH, Hong SK (1995) Mechanical allodynia is more strongly manifested in older rats in an experimental model of peripheral neuropathy. Neurosci Lett 199(2):158–160

    Article  PubMed  CAS  Google Scholar 

  63. Tanck EN, Kroin JS, McCarthy RJ, Penn RD, Ivankovich AD (1992) Effects of age and size on development of allodynia in a chronic pain model produced by sciatic nerve ligation in rats. Pain 51(3):313–316

    Article  PubMed  CAS  Google Scholar 

  64. Lovell JA, Stuesse SL, Cruce WL, Crisp T (2000) Strain differences in neuropathic hyperalgesia. Pharmacol Biochem Behav 65(1):141–144

    Article  PubMed  CAS  Google Scholar 

  65. Rode F, Thomsen M, Brolos T, Jensen DG, Blackburn-Munro G, Bjerrum OJ (2007) The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain. Eur J Pharmacol 564(1–3):103–111

    Article  PubMed  CAS  Google Scholar 

  66. Yoon YW, Lee DH, Lee BH, Chung K, Chung JM (1999) Different strains and substrains of rats show different levels of neuropathic pain behaviors. Exp Brain Res 129(2):167–171

    Article  PubMed  CAS  Google Scholar 

  67. Sotgiu ML, Biella G (2000) Differential effects of MK-801, a N-methyl-D-aspartate non-­competitive antagonist, on the dorsal horn neuron hyperactivity and hyperexcitability in neuropathic rats. Neurosci Lett 283(2):153–156

    Article  PubMed  CAS  Google Scholar 

  68. Woolf CJ (2007) Central sensitization: uncovering the relation between pain and plasticity. Anesthesiology 106(4):864–867

    Article  PubMed  Google Scholar 

  69. Stewart LSA, Martin WJ (2003) Influence of postoperative analgesics on the development of neuropathic pain in rats. Comp Med 53(1):29–36

    PubMed  CAS  Google Scholar 

  70. Dougherty PM, Garrison CJ, Carlton SM (1992) Differential influence of local anesthetic upon two models of experimentally induced peripheral mononeuropathy in the rat. Brain Res 570(1–2):109–115

    Article  PubMed  CAS  Google Scholar 

  71. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32(1):77–88

    Article  PubMed  CAS  Google Scholar 

  72. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53(1):55–63

    Article  PubMed  CAS  Google Scholar 

  73. Tal M, Bennett GJ (1994) Extra-territorial pain in rats with a peripheral mononeuropathy: mechano-hyperalgesia and mechano-allodynia in the territory of an uninjured nerve. Pain 57(3):375–382

    Article  PubMed  CAS  Google Scholar 

  74. Allchorne AJ, Broom DC, Woolf CJ (2005) Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats. Mol Pain 1:36

    Article  PubMed  Google Scholar 

  75. Mogil JS (2009) Animal models of pain: progress and challenges. Nat Rev Neurosci 10(4):283–294

    Article  PubMed  CAS  Google Scholar 

  76. Vierck JCJ (2006) Animal models of pain: lessons for drug development. In: Campbell JN, Basbaum AI, Dray R, Dubner RH, Dworkin RH, Sang CN (eds) Emerging strategies for the treatment of neuropathic pain. IASP Press, Seattle, WA, pp 475–496

    Google Scholar 

  77. Neubert JK, Widmer CG, Malphurs W, Rossi HL, Vierck JCJ, Caudle RM (2005) Use of a novel thermal operant behavioral assay for characterization of orofacial pain sensitivity. Pain 116(3):386–395

    Article  PubMed  Google Scholar 

  78. Neubert JK, King C, Malphurs W, Wong F, Weaver JP, Jenkins AC, Rossi HL, Caudle RM (2008) Characterization of mouse orofacial pain and the effects of lesioning TRPV1-expressing neurons on operant behavior. Mol Pain 4:43

    Article  PubMed  Google Scholar 

  79. Langford DJ, Bailey AL, Chanda ML, Clarke SE, Drummond TE, Echols S, Glick S, Ingrao J, Klassen-Ross T, Lacroix-Fralish ML, Matsumiya L, Sorge RE, Sotocinal SG, Tabaka JM, Wong D, van den Maagdenberg AM, Ferrari MD, Craig KD, Mogil JS (2010) Coding of facial expressions of pain in the laboratory mouse. Nat Methods 7(6):447–449

    Article  PubMed  CAS  Google Scholar 

  80. King T, Vera-Portocarrero L, Gutierrez T, Vanderah TW, Dussor G, Lai J, Fields HL, Porreca F (2009) Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci 12(11):1364–1366

    Article  PubMed  CAS  Google Scholar 

  81. Schmidtko A, Lötsch J, Freynhagen R, Geisslinger G (2010) Ziconotide for treatment of severe chronic pain. Lancet 375(9725):1569–1577

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Discipline of Anatomy & Histology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia

    Paul J. Austin

  2. School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

    Gila Moalem-Taylor

Authors
  1. Paul J. Austin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gila Moalem-Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gila Moalem-Taylor .

Editor information

Editors and Affiliations

  1. , Australian School of Advanced Medicine, Macquarie University, Technology Place 2, North Ryde, 2113, New South Wales, Australia

    Paul M. Pilowsky

  2. , Australian School of Advanced Medicine, Macquarie University, Technology Place 2, North Ryde, 2113, New South Wales, Australia

    Melissa M.J. Farnham

  3. , Australian School of Advanced Medicine, Macquarie University, Technology Place 2, North Ryde, 2113, New South Wales, Australia

    Angelina Y. Fong

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Austin, P.J., Moalem-Taylor, G. (2013). Animal Models of Neuropathic Pain Due to Nerve Injury. In: Pilowsky, P., Farnham, M., Fong, A. (eds) Stimulation and Inhibition of Neurons. Neuromethods, vol 78. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-233-9_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-233-9_14

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-232-2

  • Online ISBN: 978-1-62703-233-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation