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Comparison of three rodent neuropathic pain models

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Abstract

To characterize various animal models of neuropathic pain, we compared three previously developed rat models using the same behavioral testing methods. These models involve: (1) chronic constriction injury by loose ligation of the sciatic nerve (CCI); (2) tight ligation of the partial sciatic nerve (PSL); and (3) tight ligation of spinal nerves (SNL). Comparisons were made for the time course of behavioral signs representing various components of neuropathic pain as well as for the effects of surgical sympathectomy. In general, all three methods of peripheral nerve injury produced behavioral signs of both ongoing and evoked pain with similar time courses. However, there was a considerable difference in the magnitude of each pain component between models. Signs of mechanical allodynia were largest in the SNL injury and smallest in the CCI model. On the other hand, behavioral signs representing ongoing pain were much more prominent in the CCI model than in the other two. Although the behavioral signs of neuropathic pain tended to decrease after sympathectomy in all three models, the change was most evident in the SNL model. The results of the present study suggest that the three rat models tested have contrasting features, yet all are useful neuropathic pain models, possibly representing different populations of human neuropathic pain patients.

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References

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Blumberg H, Jänig W (1984) Discharge pattern of afferent fibers from a neuroma. Pain 20: 335–353

    Article  PubMed  CAS  Google Scholar 

  • Bonica JJ (1990) Causalgia and other reflex sympathetic dystrophies. In: Bonica JJ (ed) The management of pain. Lea & Febiger, Philadelphia, pp 220–243

    Google Scholar 

  • Campbell JN, Meyer RA, Raja SN (1992) Is nociceptor activation by alpha-1 adrenoreceptors the culprit in sympathetically maintained pain? APS J 1: 3–11

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Chung K, Kim HJ, Na HS, Park MJ, Chung JM (1993) Abnormalities of sympathetic innervation of the area of injured peripheral nerve in a rat model of neuropathic pain. Neurosci Lett 162: 85–88

    Article  PubMed  CAS  Google Scholar 

  • Chung K, Lee BH, Yoon YW, Chung JM (1996) Sympathetic sprouting in the dorsal root ganglia of the injured peripheral nerve in a rat neuropathic pain model. J Comp Neurol 376: 241–251

    Article  PubMed  CAS  Google Scholar 

  • Davar G, Hama A, Deykin A, Vos B, Maciewicz R (1991) MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy. Brain Res 553: 327–330

    Article  PubMed  CAS  Google Scholar 

  • Davies SN, Lodge D (1987) Evidence for involvement ofN-methylaspartate receptors in “wind-up” of class 2 neurones in the dorsal horn of the rat. Brain Res 424: 402–406

    Article  PubMed  CAS  Google Scholar 

  • Davis KD, Treede RD, Raja SN, Meyer RA, Campbell JN (1991) Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain. Pain 47: 309–317

    Article  PubMed  CAS  Google Scholar 

  • DeLeo JA, Coombs DW, Willenbring S, Colburn RW, Fromm C, Wagner R, Twitchell BB (1994) Characterization of a neuropathic pain model: sciatic cryoneurolysis in the rat. Pain 56: 9–16

    Article  PubMed  CAS  Google Scholar 

  • Devor M (1983) Nerve pathophysiology and mechanisms of pain in causalgia. J Auton Nerv Syst 7: 371–384

    Article  PubMed  CAS  Google Scholar 

  • Devor M, Jänig W (1981) Activation of myelinated afferents ending in a neuroma by stimulation of sympathetic supply in the rat. Neurosci Lett 24: 43–47

    Article  PubMed  CAS  Google Scholar 

  • Devor M, Jänig W, Michaelis M (1994) Modulation of activity in dorsal root ganglion neurons by sympathetic activation in nerve-injured rats. J Neurophysiol 71: 38–47

    PubMed  CAS  Google Scholar 

  • Dougherty PM, Palecek J, Zorn S, Willis WD (1993) Combined application of excitatory amino acids and substance P produces long-lasting changes in responses of primate spinothalamic tract neurons. Brain Res Rev 18: 227–246

    Article  PubMed  CAS  Google Scholar 

  • Dougherty PM, Palecek J, Paleckova V, Willis WD (1994) Neurokinin 1 and 2 antagonists prevent the synsitization of primate spinothalamic tract neurons following intradermal capsaicin. J Neurophysiol 72: 1464–1475

    PubMed  CAS  Google Scholar 

  • Dubuisson D, Dennis SG (1977) The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 4: 161–174

    Article  PubMed  CAS  Google Scholar 

  • Frost SA, Raja SN, Campbell JN, Meyer RA, Khan AA (1988) Does hyperalgesia to cooling stimuli characterize patients with sympathetically maintained pain (reflex sympathetic dystrophy)? In: Dubner R, Gebhart GF, Bond MR (eds) Proceedings of the Vth world congress on pain. Elsevier, Amsterdam, pp 151–156

    Google Scholar 

  • Furness JB, Costa M (1975) The use of glyoxylic acid for the fluorescence histochemical demonstration of peripheral stores of noradrenaline and 5-hydroxytryptamine in whole mounts. Histochemistry 41: 335–352

    Article  PubMed  CAS  Google Scholar 

  • Gracely RH, Lynch SA, Bennett GJ (1992) Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 51: 175–194

    Article  PubMed  CAS  Google Scholar 

  • Häbler H-J, Jänig W, Koltzenburg M (1987) Activation of unmyelinated afferents in chronically lesioned nerves by adrenaline and excitation of sympathetic efferents in cat. Neurosci Lett 82: 35–40

    Article  PubMed  Google Scholar 

  • Haley JE, Sullivan AF, Dickenson AH (1990) Evidence for spinalN-methyl-d-aspartate receptor involvement in prolonged chemical nociception in the rat. Brain Res 518: 218–226

    Article  PubMed  CAS  Google Scholar 

  • Kenshalo DR Jr, Leonard RB, Chung JM, Willis WD (1982) Facilitation of the responses of primate spinothalamic cells to cold and to tactile stimuli by noxious heating of the skin. Pain 12: 141–152

    Article  PubMed  Google Scholar 

  • Kim SH, Chung JM (1991) Sympathectomy alleviates mechanical allodynia in an experimental animal model for neuropathy in the rat. Neurosci Lett 134: 131–134

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Kim KJ, Yoon YW, Lee BH, Chung JM (1994) Comparison of animal models for peripheral neuropathic pain. Soc. Neurosci Abstr 20: 761

    Google Scholar 

  • Korenman EM, Devor M (1981) Ectopic adrenergic sensitivity in damaged peripheral nerve axons in the rat. Exp Neurol 72: 63–81

    Article  PubMed  CAS  Google Scholar 

  • Lee DH, Chung K, Chung JM (1995) Importance of the location of injury on sympathetic dependency of rat models of neuropathic pain. Soc. Neurosci Abstr 21: 894

    Google Scholar 

  • Mao J, Price DD, Mayer DJ, Lu J, Hayes RL (1992) Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy. Brain Res 576: 254–262

    Article  PubMed  CAS  Google Scholar 

  • McLachlan EM, Jänig W, Devor M, Michaelis M (1993) Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature 363: 543–546

    Article  PubMed  CAS  Google Scholar 

  • Mendell LM (1966) Physiological properties of unmyelinated fiver projection to the spinal cord. Exp Neurol 16: 316–332

    Article  PubMed  CAS  Google Scholar 

  • Mitchell SW (1872) Injuries of nerves and their consequences. JB Lippincott, Philadelphia, pp 252–281

    Google Scholar 

  • Na HS, Leem JW, Chung JM (1993) Abnormalities of mechanoreceptors in a rat model of neuropathic pain: possible involvement in mediating mechanical allodynia. J Neurophysiol 70: 522–528

    PubMed  CAS  Google Scholar 

  • Na HS, Han JS, Ko KH, Hong SK (1994) A behavioral model for peripheral neuropathy produced in rat's tail by inferior caudal trunk injury. Neurosci Lett 177: 50–52

    Article  PubMed  CAS  Google Scholar 

  • Neil A, Attal N, Guilbaud G (1991a) Effects of guanethidine on sensitization to natural stimuli and self-mutilating behaviour in rats with a peripheral neuropathy. Brain Res 565: 237–246

    Article  PubMed  CAS  Google Scholar 

  • Neil A, Attal N, Guilbaud G (199b) Effects of adrenergic depletion with guanethidine before and after the induction of a peripheral neuropathy on subsequent mechanical, heat and cold sensitivities in rats. In: Bond MR, Charlton JE, Woolf CJ (eds) Proceedings of the VIth world congress on pain. Elsevier, Amsterdam, pp 383–388

    Google Scholar 

  • Owens CM, Zhang D, Willis WD (1992) Changes in the response states of primate spinothalamic tract cells caused by mechanical damage of the skin or activation of descending controls. J Neurophysiol 67: 1509–1527

    PubMed  CAS  Google Scholar 

  • Richards RL (1967) Causalgia. Arch Neurol 16: 339–350

    PubMed  CAS  Google Scholar 

  • Roberts WJ (1986) A hypothesis on the physiological basis for causalgia and related pains. Pain 24: 297–311

    Article  PubMed  CAS  Google Scholar 

  • Scadding JW (1981) Development of ongoing activity, mechanosensitivity, and adrenaline sensitivity in severed peripheral nerve axons. Exp Neurol 73: 345–364

    Article  PubMed  CAS  Google Scholar 

  • Schouenborg J, Dickenson AH (1988) Long-lasting neuronal activity in rat dorsal horn evoked by impulses in cutaneous C fibres during noxious mechanical stimulation. Brain Res 439: 56–63

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Sheen K, Chung JM (1993) Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model. Brain Res 610: 62–68

    Article  PubMed  CAS  Google Scholar 

  • Sher GD, Mitchell D (1990)N-methyl-d-aspartate receptors mediate responses of rat dorsal horn neurones to hindlimb ischemia. Brain Res 522: 55–62

    Article  PubMed  CAS  Google Scholar 

  • Shir Y, Seltzer Z (1991) Effects of sympathectomy in a model of causalgiform pain produced by partial sciatic nerve injury in rats. Pain 45: 309–320

    Article  PubMed  CAS  Google Scholar 

  • Stanton-Hicks M, Jänig W, Hassenbusch S, Haddox JD, Boas R, Wilson P (1995) Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain 63: 127–133

    Article  PubMed  CAS  Google Scholar 

  • Wall PD, Gutnick M (1974) Ongoing activity in peripheral nerves: the physiology and pharmacology of impulses originating from a neuroma. Exp Neurol 43: 580–593

    Article  PubMed  CAS  Google Scholar 

  • Wall PD, Woolf CJ (1985) The brief and prolonged facilitatory effects of unmyelinated afferent input on the rat spinal cord are independently influenced by peripheral nerve injury. Neuroscience 17: 1199–1206

    Article  Google Scholar 

  • Welk E, Leah JD, Zimmermann M (1990) Characteristics of A-and C-fibers ending in a sensory nerve neuroma in the rat. J Neurophysiol 63: 759–766

    PubMed  CAS  Google Scholar 

  • Woolf CJ (1984) Long term alterations in the excitability of the flexion reflex produced by peripheral tissue injury in the chronic decerebrate rat. Pain 18: 325–344

    Article  PubMed  CAS  Google Scholar 

  • Woolf CJ, Wall PD (1986) The relative effectiveness of C-primary afferents of different origins in evoking a prolonged facilitation on the flexion reflex in the rat. J Neurosci 6: 1433–1442

    PubMed  CAS  Google Scholar 

  • Yoon YW, Na HS, Chung JM (1996) Contributions of injured and intact afferents to neuropathic pain in an experimental rat model. Pain 64: 27–36

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Marine Biomedical Institute, University of Texas Medical Branch, 301 University Boulevard, 77555-1069, Galveston, TX, USA

    Kwang Jin Kim & Jin Mo Chung

  2. Department of Anatomy and Neurosciences, University of Texas Medical Branch, 77555-1069, Galveston, TX, USA

    Jin Mo Chung

  3. Department of Physiology and Biophysics, University of Texas Medical Branch, 77555-1069, Galveston, TX, USA

    Jin Mo Chung

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  1. Kwang Jin Kim
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  2. Jin Mo Chung
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Kim, K.J., Chung, J.M. Comparison of three rodent neuropathic pain models. Exp Brain Res 113, 200–206 (1997). https://doi.org/10.1007/BF02450318

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  • DOI: https://doi.org/10.1007/BF02450318

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