Skin denervation, neuropathology, and neuropathic pain in a laser-induced focal neuropathy

Hou-Yu Chiang, Chin-Tin Chen, Hsiung-Fei Chien, Sung-Tsang Hsieh

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Small-diameter sensory nerves innervating the skin are responsive to noxious stimuli, and an injury to these nerves is presumably related to neuropathic pain. Injury-induced neuropathic pain in animals can be produced by laser irradiation, which usually requires concomitant use of photosensitive dyes, known as the photochemical approach. It is not clear whether laser irradiation alone can induce neuropathic pain. In addition, two issues are important to apply these approaches: the relationship between the extent of laser irradiation and the occurrence of neuropathic pain, and the susceptibility of small-diameter sensory nerves in the skin to laser-induced neuropathic pain. To address these issues, we designed a new model of focal neuropathy by applying a diode laser of 532 nm (100 mW) to the sciatic nerve and evaluated small-diameter nerves by quantifying skin innervation and large-diameter nerves by measuring amplitudes of the compound muscle action potential (CMAP). Immediately after laser irradiation, epineurial vessels were occluded due to the formation of thrombi, and the blood flow through these vessels was markedly reduced. On postoperative day (POD) 2, animals developed characteristic manifestations of neuropathic pain, including spontaneous pain behaviors, thermal hyperalgesia, and mechanical allodynia. These phenomena peaked during PODs 7-21, and lasted for 3-6 weeks. The neuropathology at the irradiated site of the sciatic nerve included a focal area of axonal degeneration surrounded by demyelination and endoneurial edema. The extent of damage to large-diameter motor and sensory nerves after laser irradiation was evaluated by nerve conduction studies. On the irradiated sides, amplitudes of the compound muscle action potentials and sensory nerve action potentials (SNAPs) were reduced to 65.0% (P <0.0001) and 42.5% (P <0.01) of those on the control sides, respectively. Motor innervation of the neuromuscular junctions (NMJs) on plantar muscles was examined by combined cholinesterase histochemistry and immunohistochemistry. The ratio of innervated NMJs on the operated sides decreased to 76.3% of that on the control side. Skin innervation in the territory of the irradiated sciatic nerves was evaluated by immunohistochemistry with neuronal markers. Among these markers, epidermal nerve densities for protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP) were significantly lower on the irradiated sides than the control sides with a different degree of loss for each marker (42.1-53.1%, P <0.05). Results suggest that laser-induced focal neuropathy provides a new system for studying neuropathic pain. With this approach, the extent of nerve injury can be quantified. Both small-diameter epidermal nerves and large-diameter sensory and motor nerves are susceptible to laser-induced injury of different degrees. © 2004 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)40-53
Number of pages14
JournalNeurobiology of Disease
Volume18
Issue number1
DOIs
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Neuralgia
Denervation
Lasers
Skin
Hyperalgesia
Sciatic Nerve
Action Potentials
Neuromuscular Junction
Wounds and Injuries
Muscles
Immunohistochemistry
Semiconductor Lasers
Neuropathology
Calcitonin Gene-Related Peptide
Neural Conduction
Cholinesterases
Demyelinating Diseases
Substance P
Edema
Thrombosis

Keywords

  • Epidermal nerves
  • Ischemic neuropathy
  • Laser irradiation
  • Neuropathic pain
  • Protein gene product 9.5
  • Skin innervation
  • Ubiquitin
  • biochemical marker
  • calcitonin gene related peptide
  • cholinesterase
  • gene product
  • substance P
  • allodynia
  • amplitude modulation
  • animal experiment
  • animal model
  • animal tissue
  • article
  • blood vessel
  • controlled study
  • demyelination
  • denervation
  • diode laser
  • edema
  • enzyme histochemistry
  • experimental model
  • hyperalgesia
  • immunohistochemistry
  • ischemia
  • male
  • motor nerve
  • muscle action potential
  • muscle innervation
  • nerve conduction
  • nerve fiber degeneration
  • nerve injury
  • neuromuscular synapse
  • neuropathic pain
  • neuropathology
  • nonhuman
  • peripheral neuropathy
  • plantaris muscle
  • priority journal
  • rat
  • sciatic nerve
  • sciatic neuropathy
  • sensory nerve
  • skin nerve
  • statistical significance
  • thrombogenesis
  • Animals
  • Biological Markers
  • Blood Vessels
  • Denervation
  • Disease Models, Animal
  • Disease Susceptibility
  • Lasers
  • Male
  • Nerve Fibers, Myelinated
  • Nerve Fibers, Unmyelinated
  • Neural Conduction
  • Neuralgia
  • Neuropeptides
  • Nociceptors
  • Peripheral Nervous System Diseases
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Sensory
  • Sciatic Nerve
  • Sciatic Neuropathy
  • Skin
  • Wallerian Degeneration

Cite this

Skin denervation, neuropathology, and neuropathic pain in a laser-induced focal neuropathy. / Chiang, Hou-Yu; Chen, Chin-Tin; Chien, Hsiung-Fei; Hsieh, Sung-Tsang.

In: Neurobiology of Disease, Vol. 18, No. 1, 2005, p. 40-53.

Research output: Contribution to journalArticle

Chiang, Hou-Yu ; Chen, Chin-Tin ; Chien, Hsiung-Fei ; Hsieh, Sung-Tsang. / Skin denervation, neuropathology, and neuropathic pain in a laser-induced focal neuropathy. In: Neurobiology of Disease. 2005 ; Vol. 18, No. 1. pp. 40-53.
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title = "Skin denervation, neuropathology, and neuropathic pain in a laser-induced focal neuropathy",
abstract = "Small-diameter sensory nerves innervating the skin are responsive to noxious stimuli, and an injury to these nerves is presumably related to neuropathic pain. Injury-induced neuropathic pain in animals can be produced by laser irradiation, which usually requires concomitant use of photosensitive dyes, known as the photochemical approach. It is not clear whether laser irradiation alone can induce neuropathic pain. In addition, two issues are important to apply these approaches: the relationship between the extent of laser irradiation and the occurrence of neuropathic pain, and the susceptibility of small-diameter sensory nerves in the skin to laser-induced neuropathic pain. To address these issues, we designed a new model of focal neuropathy by applying a diode laser of 532 nm (100 mW) to the sciatic nerve and evaluated small-diameter nerves by quantifying skin innervation and large-diameter nerves by measuring amplitudes of the compound muscle action potential (CMAP). Immediately after laser irradiation, epineurial vessels were occluded due to the formation of thrombi, and the blood flow through these vessels was markedly reduced. On postoperative day (POD) 2, animals developed characteristic manifestations of neuropathic pain, including spontaneous pain behaviors, thermal hyperalgesia, and mechanical allodynia. These phenomena peaked during PODs 7-21, and lasted for 3-6 weeks. The neuropathology at the irradiated site of the sciatic nerve included a focal area of axonal degeneration surrounded by demyelination and endoneurial edema. The extent of damage to large-diameter motor and sensory nerves after laser irradiation was evaluated by nerve conduction studies. On the irradiated sides, amplitudes of the compound muscle action potentials and sensory nerve action potentials (SNAPs) were reduced to 65.0{\%} (P <0.0001) and 42.5{\%} (P <0.01) of those on the control sides, respectively. Motor innervation of the neuromuscular junctions (NMJs) on plantar muscles was examined by combined cholinesterase histochemistry and immunohistochemistry. The ratio of innervated NMJs on the operated sides decreased to 76.3{\%} of that on the control side. Skin innervation in the territory of the irradiated sciatic nerves was evaluated by immunohistochemistry with neuronal markers. Among these markers, epidermal nerve densities for protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP) were significantly lower on the irradiated sides than the control sides with a different degree of loss for each marker (42.1-53.1{\%}, P <0.05). Results suggest that laser-induced focal neuropathy provides a new system for studying neuropathic pain. With this approach, the extent of nerve injury can be quantified. Both small-diameter epidermal nerves and large-diameter sensory and motor nerves are susceptible to laser-induced injury of different degrees. {\circledC} 2004 Elsevier Inc. All rights reserved.",
keywords = "Epidermal nerves, Ischemic neuropathy, Laser irradiation, Neuropathic pain, Protein gene product 9.5, Skin innervation, Ubiquitin, biochemical marker, calcitonin gene related peptide, cholinesterase, gene product, substance P, allodynia, amplitude modulation, animal experiment, animal model, animal tissue, article, blood vessel, controlled study, demyelination, denervation, diode laser, edema, enzyme histochemistry, experimental model, hyperalgesia, immunohistochemistry, ischemia, male, motor nerve, muscle action potential, muscle innervation, nerve conduction, nerve fiber degeneration, nerve injury, neuromuscular synapse, neuropathic pain, neuropathology, nonhuman, peripheral neuropathy, plantaris muscle, priority journal, rat, sciatic nerve, sciatic neuropathy, sensory nerve, skin nerve, statistical significance, thrombogenesis, Animals, Biological Markers, Blood Vessels, Denervation, Disease Models, Animal, Disease Susceptibility, Lasers, Male, Nerve Fibers, Myelinated, Nerve Fibers, Unmyelinated, Neural Conduction, Neuralgia, Neuropeptides, Nociceptors, Peripheral Nervous System Diseases, Rats, Rats, Sprague-Dawley, Receptors, Sensory, Sciatic Nerve, Sciatic Neuropathy, Skin, Wallerian Degeneration",
author = "Hou-Yu Chiang and Chin-Tin Chen and Hsiung-Fei Chien and Sung-Tsang Hsieh",
note = "被引用次數:22 Export Date: 16 March 2016 CODEN: NUDIE 通訊地址: Dept. of Anatomy and Cell Biology, Natl. Taiwan Univ. Coll. of Medicine, Taipei 10018, TaiwanTaiwan; 電子郵件: sthsieh@ntumc.org 化學物質/CAS: calcitonin gene related peptide, 83652-28-2; cholinesterase, 9001-08-5; substance P, 33507-63-0; Biological Markers; Neuropeptides 參考文獻: Basbaum, A.I., 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 (1991) Pain, 47, pp. 359-367; Bennett, G.J., Xie, Y.K., A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man (1988) Pain, 33, pp. 87-107; Chaplan, S.R., Bach, F.W., Pogrel, J.W., Chung, J.M., Yaksh, T.L., Quantitative assessment of tactile allodynia in the rat paw (1994) J. Neurosci. Methods, 53, pp. 55-63; Craig, A.D., Pain mechanisms: Labeled lines versus convergence in central processing (2003) Annu. Rev. Neurosci., 26, pp. 1-30; Decosterd, I., Woolf, C.J., Spared nerve injury: An animal model of persistent peripheral neuropathic pain (2000) Pain, 87, pp. 149-158; Dolmans, D.E., Fukumura, D., Jain, R.K., Photodynamic therapy for cancer (2003) Nat. Rev., Cancer, 3, pp. 380-387; Doubell, T.P., Woolf, C.J., Growth-associated protein 43 immunoreactivity in the superficial dorsal horn of the rat spinal cord is localized in atrophic C-fiber, and not in sprouted A-fiber, central terminals after peripheral nerve injury (1997) J. Comp. Neurol., 386, pp. 111-118; Gautron, M., Jazat, F., Ratinahirana, H., Hauw, J.J., Guilbaud, G., Alterations in myelinated fibres in the sciatic nerve of rats after constriction: Possible relationships between the presence of abnormal small myelinated fibres and pain-related behaviour (1990) Neurosci. Lett., 111, pp. 28-33; Gazelius, B., Cui, J.G., Svensson, M., Meyerson, B., Linderoth, B., Photochemically induced ischaemic lesion of the rat sciatic nerve. A novel method providing high incidence of mononeuropathy (1996) NeuroReport, 7, pp. 2619-2623; Guilbaud, G., Gautron, M., Jazat, F., Ratinahirana, H., Hassig, R., Hauw, J.J., Time course of degeneration and regeneration of myelinated nerve fibres following chronic loose ligatures of the rat sciatic nerve: Can nerve lesions be linked to the abnormal pain-related behaviours? (1993) Pain, 53, pp. 147-158; Hao, J.X., Blakeman, K.H., Yu, W., Hultenby, K., Xu, X.J., Wiesenfeld-Hallin, Z., Development of a mouse model of neuropathic pain following photochemically induced ischemia in the sciatic nerve (2000) Exp. Neurol., 163, pp. 231-238; Hargreaves, K., Dubner, R., Brown, F., Flores, C., Joris, J., A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia (1988) Pain, 32, pp. 77-88; Hegde, A.N., Inokuchi, K., Pei, W., Casadio, A., Ghirardi, M., Chain, D.G., Martin, K.C., Schwartz, J.H., Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia (1997) Cell, 89, pp. 115-126; Hilliges, M., Wang, L., Johansson, O., Ultrastructural evidence for nerve fibers within all vital layers of the human epidermis (1995) J. Invest. Dermatol., 104, pp. 134-137; Holland, N.R., Stocks, A., Hauer, P., Cornblath, D.R., Griffin, J.W., McArthur, J.C., Intraepidermal nerve fiber density in patients with painful sensory neuropathy (1997) Neurology, 48, pp. 708-711; Hsieh, S.T., Chiang, H.Y., Lin, W.M., Pathology of nerve terminal degeneration in the skin (2000) J. Neuropathol. Exp. Neurol., 59, pp. 297-307; Committee, I., Ethical standards for investigations of experimental pain in animals. The committee for research and ethical issues of the International Association for the Study of Pain (1980) Pain, 9, pp. 141-143; Iida, H., Schmelzer, J.D., Schmeichel, A.M., Wang, Y., Low, P.A., Peripheral nerve ischemia: Reperfusion injury and fiber regeneration (2003) Exp. Neurol., 184, pp. 997-1002; Kennedy, W.R., Said, G., Sensory nerves in skin: Answers about painful feet? (1999) Neurology, 53, pp. 1614-1615; Ko, M.H., Chen, W.P., Lin-Shiau, S.Y., Hsieh, S.T., Age-dependent acrylamide neurotoxicity in mice: Morphology, physiology, and function (1999) Exp. Neurol., 158, pp. 37-46; Kupers, R.C., Nuytten, D., Castro-Costa, M., Gybels, J.M., A time course analysis of the changes in spontaneous and evoked behaviour in a rat model of neuropathic pain (1992) Pain, 50, pp. 101-111; Kupers, R., Yu, W., Persson, J.K., Xu, X.J., Wiesenfeld-Hallin, Z., Photochemically-induced ischemia of the rat sciatic nerve produces a dose-dependent and highly reproducible mechanical, heat and cold allodynia, and signs of spontaneous pain (1998) Pain, 76, pp. 45-59; Lin, W.M., Hsieh, S.T., Huang, I.T., Griffin, J.W., Chen, W.P., Ultrastructural localization and regulation of protein gene product 9.5 (1997) NeuroReport, 8, pp. 2999-3004; Lin, Y.W., Tseng, T.J., Lin, W.M., Hsieh, S.T., Cutaneous nerve terminal degeneration in painful mononeuropathy (2001) Exp. Neurol., 170, pp. 290-296; Lindenlaub, T., Sommer, C., Epidermal innervation density after partial sciatic nerve lesion and pain-related behavior in the rat (2002) Acta. Neuropathol. (Berl.), 104, pp. 137-143; Ma, W., Bisby, M.A., 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 (2000) J. Neurocytol., 29, pp. 249-262; Malmberg, A.B., Basbaum, A.I., Partial sciatic nerve injury in the mouse as a model of neuropathic pain: Behavioral and neuroanatomical correlates (1998) Pain, 76, pp. 215-222; Menovsky, T., Van Den Berghweerman, M., Beek, J.F., Effect of CO 2 milliwatt laser on peripheral nerves: Part I. A dose-response study (1996) Microsurgery, 17, pp. 562-567; Menovsky, T., Van Den Berghweerman, M., Beek, J.F., Effect of CO 2 milliwatt laser on peripheral nerves: Part II. A histological and functional study (2000) Microsurgery, 20, pp. 150-155; Morris, S.J., Kunzek, S., Shore, A.C., The effect of acetylcholine on finger capillary pressure and capillary flow in healthy volunteers (1996) J. Physiol., 494, pp. 307-313; Myers, R.R., James, H.E., Powell, H.C., Laser injury of peripheral nerve: A model for focal endoneurial damage (1985) J. Neurol. Neurosurg. Psychiatry, 48, pp. 1265-1268; Myers, R.R., Heckman, H.M., Powell, H.C., Axonal viability and the persistence of thermal hyperalgesia after partial freeze lesions of nerve (1996) J. Neurol. Sci., 139, pp. 28-38; Nakuda, H., Lynch, C.D.P., McMorran, P.D., Aggravated reperfusion injury in STZ-diabetic nerve (2002) J. Peripher. Nerv. Syst., 7, pp. 37-43; Nuytten, D., Kupers, R., Lammens, M., Dom, R., Van Hees, J., Gybels, J., Further evidence for myelinated as well as unmyelinated fibre damage in a rat model of neuropathic pain (1992) Exp. Brain Res., 91, pp. 73-78; Oaklander, A.L., Romans, K., Horasek, S., Stocks, A., Hauer, P., Meyer, R.A., Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage (1998) Ann. Neurol., 44, pp. 789-795; Parry, G.J., Brown, M.J., Selective fiber vulnerability in acute ischemic neuropathy (1982) Ann. Neurol., 11, pp. 147-154; Periquet, M.I., Novak, V., Collins, M.P., Nagaraja, H.N., Erdem, S., Nash, S.M., Freimer, M.L., Mendell, J.R., Painful sensory neuropathy: Prospective evaluation using skin biopsy (1999) Neurology, 53, pp. 1641-1647; Rosen, E.D., Raymond, S., Zollman, A., Noria, F., Sandoval-Cooper, M., Shulman, A., Merz, J.L., Castellino, F.J., Laser-induced noninvasive vascular injury models in mice generate platelet- and coagulation-dependent thrombi (2001) Am. J. Pathol., 158, pp. 1613-1622; Seltzer, Z., Dubner, R., Shir, Y., A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury (1990) Pain, 43, pp. 205-218; Vaalasti, A., Tainio, H., Johansson, O., Rechardt, L., Light and electron microscopic immunocytochemical demonstration of intraepidermal CGRP-containing nerves in human skin (1988) Skin. Pharmacol., 1, pp. 225-229; Vital, A., Vital, C., Brechenmacher, C., Serise, J.M., Callen, S., Nicolau, H., Videau, J., Quantitative, histological and ultrastructural studies of peripheral nerve in arteriosclerotic non-diabetic patients (1986) Clin. Neuropathol., 5, pp. 224-229; Wagner, R., Deleo, J.A., Heckman, H.M., Myers, R.R., Peripheral nerve pathology following sciatic cryoneurolysis: Relationship to neuropathic behaviors in the rat (1995) Exp. Neurol., 133, pp. 256-264; Wang, L., Hilliges, M., Jernberg, T., Wiegleb-Edstronom, D., Johansson, O., Protein gene product 9.5-immunoreactive nerve fibers and cells in human skin (1990) Cell Tissue Res., 261, pp. 25-33; Woolf, C.J., Pain (2000) Neurobiol. Dis., 7, pp. 504-510; Zimmermann, M., Ethical guidelines for investigations of experimental pain in conscious animals (1983) Pain, 16, pp. 109-110",
year = "2005",
doi = "10.1016/j.nbd.2004.09.006",
language = "English",
volume = "18",
pages = "40--53",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Skin denervation, neuropathology, and neuropathic pain in a laser-induced focal neuropathy

AU - Chiang, Hou-Yu

AU - Chen, Chin-Tin

AU - Chien, Hsiung-Fei

AU - Hsieh, Sung-Tsang

N1 - 被引用次數:22 Export Date: 16 March 2016 CODEN: NUDIE 通訊地址: Dept. of Anatomy and Cell Biology, Natl. Taiwan Univ. Coll. of Medicine, Taipei 10018, TaiwanTaiwan; 電子郵件: sthsieh@ntumc.org 化學物質/CAS: calcitonin gene related peptide, 83652-28-2; cholinesterase, 9001-08-5; substance P, 33507-63-0; Biological Markers; Neuropeptides 參考文獻: Basbaum, A.I., 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 (1991) Pain, 47, pp. 359-367; Bennett, G.J., Xie, Y.K., A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man (1988) Pain, 33, pp. 87-107; Chaplan, S.R., Bach, F.W., Pogrel, J.W., Chung, J.M., Yaksh, T.L., Quantitative assessment of tactile allodynia in the rat paw (1994) J. Neurosci. Methods, 53, pp. 55-63; Craig, A.D., Pain mechanisms: Labeled lines versus convergence in central processing (2003) Annu. Rev. Neurosci., 26, pp. 1-30; Decosterd, I., Woolf, C.J., Spared nerve injury: An animal model of persistent peripheral neuropathic pain (2000) Pain, 87, pp. 149-158; Dolmans, D.E., Fukumura, D., Jain, R.K., Photodynamic therapy for cancer (2003) Nat. Rev., Cancer, 3, pp. 380-387; Doubell, T.P., Woolf, C.J., Growth-associated protein 43 immunoreactivity in the superficial dorsal horn of the rat spinal cord is localized in atrophic C-fiber, and not in sprouted A-fiber, central terminals after peripheral nerve injury (1997) J. Comp. Neurol., 386, pp. 111-118; Gautron, M., Jazat, F., Ratinahirana, H., Hauw, J.J., Guilbaud, G., Alterations in myelinated fibres in the sciatic nerve of rats after constriction: Possible relationships between the presence of abnormal small myelinated fibres and pain-related behaviour (1990) Neurosci. Lett., 111, pp. 28-33; Gazelius, B., Cui, J.G., Svensson, M., Meyerson, B., Linderoth, B., Photochemically induced ischaemic lesion of the rat sciatic nerve. A novel method providing high incidence of mononeuropathy (1996) NeuroReport, 7, pp. 2619-2623; Guilbaud, G., Gautron, M., Jazat, F., Ratinahirana, H., Hassig, R., Hauw, J.J., Time course of degeneration and regeneration of myelinated nerve fibres following chronic loose ligatures of the rat sciatic nerve: Can nerve lesions be linked to the abnormal pain-related behaviours? (1993) Pain, 53, pp. 147-158; Hao, J.X., Blakeman, K.H., Yu, W., Hultenby, K., Xu, X.J., Wiesenfeld-Hallin, Z., Development of a mouse model of neuropathic pain following photochemically induced ischemia in the sciatic nerve (2000) Exp. Neurol., 163, pp. 231-238; Hargreaves, K., Dubner, R., Brown, F., Flores, C., Joris, J., A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia (1988) Pain, 32, pp. 77-88; Hegde, A.N., Inokuchi, K., Pei, W., Casadio, A., Ghirardi, M., Chain, D.G., Martin, K.C., Schwartz, J.H., Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia (1997) Cell, 89, pp. 115-126; Hilliges, M., Wang, L., Johansson, O., Ultrastructural evidence for nerve fibers within all vital layers of the human epidermis (1995) J. Invest. Dermatol., 104, pp. 134-137; Holland, N.R., Stocks, A., Hauer, P., Cornblath, D.R., Griffin, J.W., McArthur, J.C., Intraepidermal nerve fiber density in patients with painful sensory neuropathy (1997) Neurology, 48, pp. 708-711; Hsieh, S.T., Chiang, H.Y., Lin, W.M., Pathology of nerve terminal degeneration in the skin (2000) J. Neuropathol. Exp. Neurol., 59, pp. 297-307; Committee, I., Ethical standards for investigations of experimental pain in animals. The committee for research and ethical issues of the International Association for the Study of Pain (1980) Pain, 9, pp. 141-143; Iida, H., Schmelzer, J.D., Schmeichel, A.M., Wang, Y., Low, P.A., Peripheral nerve ischemia: Reperfusion injury and fiber regeneration (2003) Exp. Neurol., 184, pp. 997-1002; Kennedy, W.R., Said, G., Sensory nerves in skin: Answers about painful feet? (1999) Neurology, 53, pp. 1614-1615; Ko, M.H., Chen, W.P., Lin-Shiau, S.Y., Hsieh, S.T., Age-dependent acrylamide neurotoxicity in mice: Morphology, physiology, and function (1999) Exp. Neurol., 158, pp. 37-46; Kupers, R.C., Nuytten, D., Castro-Costa, M., Gybels, J.M., A time course analysis of the changes in spontaneous and evoked behaviour in a rat model of neuropathic pain (1992) Pain, 50, pp. 101-111; Kupers, R., Yu, W., Persson, J.K., Xu, X.J., Wiesenfeld-Hallin, Z., Photochemically-induced ischemia of the rat sciatic nerve produces a dose-dependent and highly reproducible mechanical, heat and cold allodynia, and signs of spontaneous pain (1998) Pain, 76, pp. 45-59; Lin, W.M., Hsieh, S.T., Huang, I.T., Griffin, J.W., Chen, W.P., Ultrastructural localization and regulation of protein gene product 9.5 (1997) NeuroReport, 8, pp. 2999-3004; Lin, Y.W., Tseng, T.J., Lin, W.M., Hsieh, S.T., Cutaneous nerve terminal degeneration in painful mononeuropathy (2001) Exp. Neurol., 170, pp. 290-296; Lindenlaub, T., Sommer, C., Epidermal innervation density after partial sciatic nerve lesion and pain-related behavior in the rat (2002) Acta. Neuropathol. (Berl.), 104, pp. 137-143; Ma, W., Bisby, M.A., 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 (2000) J. Neurocytol., 29, pp. 249-262; Malmberg, A.B., Basbaum, A.I., Partial sciatic nerve injury in the mouse as a model of neuropathic pain: Behavioral and neuroanatomical correlates (1998) Pain, 76, pp. 215-222; Menovsky, T., Van Den Berghweerman, M., Beek, J.F., Effect of CO 2 milliwatt laser on peripheral nerves: Part I. A dose-response study (1996) Microsurgery, 17, pp. 562-567; Menovsky, T., Van Den Berghweerman, M., Beek, J.F., Effect of CO 2 milliwatt laser on peripheral nerves: Part II. A histological and functional study (2000) Microsurgery, 20, pp. 150-155; Morris, S.J., Kunzek, S., Shore, A.C., The effect of acetylcholine on finger capillary pressure and capillary flow in healthy volunteers (1996) J. Physiol., 494, pp. 307-313; Myers, R.R., James, H.E., Powell, H.C., Laser injury of peripheral nerve: A model for focal endoneurial damage (1985) J. Neurol. Neurosurg. Psychiatry, 48, pp. 1265-1268; Myers, R.R., Heckman, H.M., Powell, H.C., Axonal viability and the persistence of thermal hyperalgesia after partial freeze lesions of nerve (1996) J. Neurol. Sci., 139, pp. 28-38; Nakuda, H., Lynch, C.D.P., McMorran, P.D., Aggravated reperfusion injury in STZ-diabetic nerve (2002) J. Peripher. Nerv. Syst., 7, pp. 37-43; Nuytten, D., Kupers, R., Lammens, M., Dom, R., Van Hees, J., Gybels, J., Further evidence for myelinated as well as unmyelinated fibre damage in a rat model of neuropathic pain (1992) Exp. Brain Res., 91, pp. 73-78; Oaklander, A.L., Romans, K., Horasek, S., Stocks, A., Hauer, P., Meyer, R.A., Unilateral postherpetic neuralgia is associated with bilateral sensory neuron damage (1998) Ann. Neurol., 44, pp. 789-795; Parry, G.J., Brown, M.J., Selective fiber vulnerability in acute ischemic neuropathy (1982) Ann. Neurol., 11, pp. 147-154; Periquet, M.I., Novak, V., Collins, M.P., Nagaraja, H.N., Erdem, S., Nash, S.M., Freimer, M.L., Mendell, J.R., Painful sensory neuropathy: Prospective evaluation using skin biopsy (1999) Neurology, 53, pp. 1641-1647; Rosen, E.D., Raymond, S., Zollman, A., Noria, F., Sandoval-Cooper, M., Shulman, A., Merz, J.L., Castellino, F.J., Laser-induced noninvasive vascular injury models in mice generate platelet- and coagulation-dependent thrombi (2001) Am. J. 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PY - 2005

Y1 - 2005

N2 - Small-diameter sensory nerves innervating the skin are responsive to noxious stimuli, and an injury to these nerves is presumably related to neuropathic pain. Injury-induced neuropathic pain in animals can be produced by laser irradiation, which usually requires concomitant use of photosensitive dyes, known as the photochemical approach. It is not clear whether laser irradiation alone can induce neuropathic pain. In addition, two issues are important to apply these approaches: the relationship between the extent of laser irradiation and the occurrence of neuropathic pain, and the susceptibility of small-diameter sensory nerves in the skin to laser-induced neuropathic pain. To address these issues, we designed a new model of focal neuropathy by applying a diode laser of 532 nm (100 mW) to the sciatic nerve and evaluated small-diameter nerves by quantifying skin innervation and large-diameter nerves by measuring amplitudes of the compound muscle action potential (CMAP). Immediately after laser irradiation, epineurial vessels were occluded due to the formation of thrombi, and the blood flow through these vessels was markedly reduced. On postoperative day (POD) 2, animals developed characteristic manifestations of neuropathic pain, including spontaneous pain behaviors, thermal hyperalgesia, and mechanical allodynia. These phenomena peaked during PODs 7-21, and lasted for 3-6 weeks. The neuropathology at the irradiated site of the sciatic nerve included a focal area of axonal degeneration surrounded by demyelination and endoneurial edema. The extent of damage to large-diameter motor and sensory nerves after laser irradiation was evaluated by nerve conduction studies. On the irradiated sides, amplitudes of the compound muscle action potentials and sensory nerve action potentials (SNAPs) were reduced to 65.0% (P <0.0001) and 42.5% (P <0.01) of those on the control sides, respectively. Motor innervation of the neuromuscular junctions (NMJs) on plantar muscles was examined by combined cholinesterase histochemistry and immunohistochemistry. The ratio of innervated NMJs on the operated sides decreased to 76.3% of that on the control side. Skin innervation in the territory of the irradiated sciatic nerves was evaluated by immunohistochemistry with neuronal markers. Among these markers, epidermal nerve densities for protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP) were significantly lower on the irradiated sides than the control sides with a different degree of loss for each marker (42.1-53.1%, P <0.05). Results suggest that laser-induced focal neuropathy provides a new system for studying neuropathic pain. With this approach, the extent of nerve injury can be quantified. Both small-diameter epidermal nerves and large-diameter sensory and motor nerves are susceptible to laser-induced injury of different degrees. © 2004 Elsevier Inc. All rights reserved.

AB - Small-diameter sensory nerves innervating the skin are responsive to noxious stimuli, and an injury to these nerves is presumably related to neuropathic pain. Injury-induced neuropathic pain in animals can be produced by laser irradiation, which usually requires concomitant use of photosensitive dyes, known as the photochemical approach. It is not clear whether laser irradiation alone can induce neuropathic pain. In addition, two issues are important to apply these approaches: the relationship between the extent of laser irradiation and the occurrence of neuropathic pain, and the susceptibility of small-diameter sensory nerves in the skin to laser-induced neuropathic pain. To address these issues, we designed a new model of focal neuropathy by applying a diode laser of 532 nm (100 mW) to the sciatic nerve and evaluated small-diameter nerves by quantifying skin innervation and large-diameter nerves by measuring amplitudes of the compound muscle action potential (CMAP). Immediately after laser irradiation, epineurial vessels were occluded due to the formation of thrombi, and the blood flow through these vessels was markedly reduced. On postoperative day (POD) 2, animals developed characteristic manifestations of neuropathic pain, including spontaneous pain behaviors, thermal hyperalgesia, and mechanical allodynia. These phenomena peaked during PODs 7-21, and lasted for 3-6 weeks. The neuropathology at the irradiated site of the sciatic nerve included a focal area of axonal degeneration surrounded by demyelination and endoneurial edema. The extent of damage to large-diameter motor and sensory nerves after laser irradiation was evaluated by nerve conduction studies. On the irradiated sides, amplitudes of the compound muscle action potentials and sensory nerve action potentials (SNAPs) were reduced to 65.0% (P <0.0001) and 42.5% (P <0.01) of those on the control sides, respectively. Motor innervation of the neuromuscular junctions (NMJs) on plantar muscles was examined by combined cholinesterase histochemistry and immunohistochemistry. The ratio of innervated NMJs on the operated sides decreased to 76.3% of that on the control side. Skin innervation in the territory of the irradiated sciatic nerves was evaluated by immunohistochemistry with neuronal markers. Among these markers, epidermal nerve densities for protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP) were significantly lower on the irradiated sides than the control sides with a different degree of loss for each marker (42.1-53.1%, P <0.05). Results suggest that laser-induced focal neuropathy provides a new system for studying neuropathic pain. With this approach, the extent of nerve injury can be quantified. Both small-diameter epidermal nerves and large-diameter sensory and motor nerves are susceptible to laser-induced injury of different degrees. © 2004 Elsevier Inc. All rights reserved.

KW - Epidermal nerves

KW - Ischemic neuropathy

KW - Laser irradiation

KW - Neuropathic pain

KW - Protein gene product 9.5

KW - Skin innervation

KW - Ubiquitin

KW - biochemical marker

KW - calcitonin gene related peptide

KW - cholinesterase

KW - gene product

KW - substance P

KW - allodynia

KW - amplitude modulation

KW - animal experiment

KW - animal model

KW - animal tissue

KW - article

KW - blood vessel

KW - controlled study

KW - demyelination

KW - denervation

KW - diode laser

KW - edema

KW - enzyme histochemistry

KW - experimental model

KW - hyperalgesia

KW - immunohistochemistry

KW - ischemia

KW - male

KW - motor nerve

KW - muscle action potential

KW - muscle innervation

KW - nerve conduction

KW - nerve fiber degeneration

KW - nerve injury

KW - neuromuscular synapse

KW - neuropathic pain

KW - neuropathology

KW - nonhuman

KW - peripheral neuropathy

KW - plantaris muscle

KW - priority journal

KW - rat

KW - sciatic nerve

KW - sciatic neuropathy

KW - sensory nerve

KW - skin nerve

KW - statistical significance

KW - thrombogenesis

KW - Animals

KW - Biological Markers

KW - Blood Vessels

KW - Denervation

KW - Disease Models, Animal

KW - Disease Susceptibility

KW - Lasers

KW - Male

KW - Nerve Fibers, Myelinated

KW - Nerve Fibers, Unmyelinated

KW - Neural Conduction

KW - Neuralgia

KW - Neuropeptides

KW - Nociceptors

KW - Peripheral Nervous System Diseases

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Sensory

KW - Sciatic Nerve

KW - Sciatic Neuropathy

KW - Skin

KW - Wallerian Degeneration

U2 - 10.1016/j.nbd.2004.09.006

DO - 10.1016/j.nbd.2004.09.006

M3 - Article

VL - 18

SP - 40

EP - 53

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 1

ER -