Behavioral, electrophysiological, and morphological correlates,, M. Gaviria, H. Haton, F. Sandillon, and A. Privat, A mouse model of acute ischemic spinal cord injury,, J. X. Hao, T. Sthr, N. Selve, Z. Wiesenfeld-Hallin, and X. J. Xu, Lacosamide, a new anti-epileptic, alleviates neuropathic pain-like behaviors in rat models of spinal cord or trigeminal nerve injury,, M. von Heijne, J. X. Hao, A. Sollevi, and X. J. Xu, Effects of intrathecal morphine, baclofen, clonidine and R-PIA on the acute allodynia-like behaviours after spinal cord ischaemia in rats,, J. X. Hao, X. J. Xu, H. Aldskogius, A. Seiger, and Z. Wiesenfeld-Hallin, Photochemically induced transient spinal ischemia induces behavioral hypersensitivity to mechanical and cold stimuli, but not to noxious-heat stimuli, in the rat,, W. P. Wu, J. X. Hao, X. J. Xu, Z. Wiesenfeld-Hallin, W. Koek, and F. C. Colpaert, The very-high-efficacy 5-HT receptor agonist, F 13640, preempts the development of allodynia-like behaviors in rats with spinal cord injury,, J. X. Hao, X. J. Xu, Y. X. Yu, A. Seiger, and Z. Wiesenfeld-Hallin, Transient spinal cord ischemia induces temporary hypersensitivity of dorsal horn wide dynamic range neurons to myelinated, but not unmyelinated, fiber input,, J. X. Hao, X. J. Xu, Y. X. Yu, A. Seiger, and Z. Wiesenfeld-Hallin, Hypersensitivity of dorsal horn wide dynamic range neurons to cutaneous mechanical stimuli after transient spinal cord ischemia in the rat,, D. M. Basso, M. S. Beattie, and J. C. Bresnahan, A sensitive and reliable locomotor rating scale for open field testing in rats,, K. Gale, H. Kerasidis, and J. R. Wrathall, Spinal cord contusion in the rat: behavioral analysis of functional neurologic impairment,, C. A. Fairbanks, K. L. Schreiber, K. L. Brewer et al., Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury,, R. P. Yezierski, S. Liu, G. L. Ruenes, K. J. Kajander, and K. L. Brewer, Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model,, P. Siddall, C. L. Xu, and M. Cousins, Allodynia following traumatic spinal cord injury in the rat,, M. G. Fehlings and C. H. Tator, The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury,, R. Nashmi and M. G. Fehlings, Changes in axonal physiology and morphology after chronic compressive injury of the rat thoracic spinal cord,, J. C. Bruce, M. A. Oatway, and L. C. Weaver, Chronic pain after clip-compression injury of the rat spinal cord,, S. A. Marques, V. F. Garcez, E. A. Del Bel, and A. M.B. However, it is likely that too many genes are involved [26]. Mechanical allodynia can be measured in various ways using the von Frey hair. This website uses cookies. Battistuzzo CR, Callister RJ, Callister R, Galea MP. Muscle spasm pain is a commonly observed type of musculoskeletal pain and is refractory for treatment of common musculoskeletal pain; analgesics are sometimes helpful, but antispasticity treatment may be needed in many cases [18]. The pathology of human SCI is not greatly different from that of experimental animals, although important specific differences exist. During motor dysfunction, visceral pain-related behavior is difficult to analyze. Bunge MB, Holets VR, Bates ML, Clarke TS, Watson BD. Spinal cord injury. These include contusion impactors (Krishna et al., 2013) and clip compression (Alluin et al., 2011). Clip compression injury resembles spinal contusion injury at the point of the injury caused by pressure to the spinal cord. The development of reliable neurotrauma mouse models provides great promise for evaluating overexpression or inactivation of certain genes on lesion pathophysiology and functional outcome. 1981;6:315335, 12. However, the direct translation of the results from rodents to clinical cases is difficult because of neurofunctional and anatomic differences between the two species. A. Gruner, A monitored contusion model of spinal cord injury in the rat,, A. Nakae, K. Nakai, T. Tanaka et al., Serotonin2C receptor mRNA editing in neuropathic pain model,, E. D. Crown, Z. Ye, K. M. Johnson, G. Y. Xu, D. J. McAdoo, and C. E. Hulsebosch, Increases in the activated forms of ERK 1/2, p38 MAPK, and CREB are correlated with the expression of at-level mechanical allodynia following spinal cord injury,, J. G. Meisner, A. D. Marsh, and D. R. Marsh, Loss of GABAergic interneurons in laminae I-III of the spinal cord dorsal horn contributes to reduced GABAergic tone and neuropathic pain after spinal cord injury,, E. L. Hoschouer, D. M. Basso, and L. B. Jakeman, Aberrant sensory responses are dependent on lesion severity after spinal cord contusion injury in mice,, C. M. Mann, J. H. T. Lee, J. Hillyer, A. M. T. Stammers, W. Tetzlaff, and B. K. Kwon, Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury,, S. M. Carlton, J. Lee, S. Tigchelaar, J. Liu et al., Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury,, J. Kim, J. I. Jung, H. S. Na, S. K. Hong, and Y. W. Yoon, Effects of morphine on mechanical allodynia in a rat model of central neuropathic pain,, B. C. Hains, K. M. Johnson, D. J. McAdoo, M. J. Eaton, and C. E. Hulsebosch, Engraftment of serotonergic precursors enhances locomotor function and attenuates chronic central pain behavior following spinal hemisection injury in the rat,, B. D. Watson, R. Prado, and W. D. Dietrich, Photochemically induced spinal cord injury in the rat,, J. X. Hao, X. J. Xu, H. Aldskogius, A. Seiger, and Z. Wiesenfeld-Hallin, The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat,, J. X. Hao, X. J. Xu, H. Aldskogius, A. Seiger, and Z. Wiesenfeld-Hallin, Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation,, H. K. Erichsen, J. X. Hao, X. J. Xu, and G. Blackburn-Munro, Comparative actions of the opioid analgesics morphine, methadone and codeine in rat models of peripheral and central neuropathic pain,, X. J. Xu, J. X. Hao, H. Aldskogius, A. Seiger, and Z. Wiesenfeld-Hallin, Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury,, R. Prado, W. D. Dietrich, B. D. Watson, M. D. Ginsberg, and B. Zeman RJ, Wen X, Ouyang N, Rocchio R, Shih L, Alfieri A, Moorthy C, Etlinger JD. 2010;225:219230, 24. To accurately evaluate ischemic injury of the spinal cord, endoprosthesis implantation in the thoraco-abdominal aorta has been used (Vaquero et al., 2007). Your message has been successfully sent to your colleague. Following laminectomy, spinal cord transection is performed with spring scissors. Spinal cord injury leads to immediate impaired motor and sensory functions, which are also manifested over time. The utility for each model summarizes in Table 3. The thoracic spinal cord contusion model is the most popular pain research model and is induced with impactors, such as the weight-drop impactor [36]. In thoracic spinal cord injury, trunk allodynia reflects at-level neuropathic pain, and allodynia in the hindlimb reflects below-level neuropathic pain. Nonetheless, the subjectivity of these measures has led to a decade-long search for surrogate biomarkers. Some models are used for investigating pathophysiological mechanisms (Table 2) and others for investigating the mechanisms underlying tissue engineering and spinal cord regeneration (Table 2). Corresponding author: Mingxing Ding, Department of Medical Sciences, Jinhua Polytechnic, Jinhua 321007, Zhejiang Province, China; Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang Province, China, . A. Du, H. Y. Tan et al., Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury,, T. Furuya, M. Hashimoto, M. Koda et al., Treatment of rat spinal cord injury with a Rho-kinase inhibitor and bone marrow stromal cell transplantation,, I. D. Hentall and S. B. Burns, Restorative effects of stimulating medullary raphe after spinal cord injury,, M. A. Hook, G. Moreno, S. Woller et al., Intrathecal morphine attenuates recovery of function after a spinal cord injury,, S. Lord-Fontaine, F. Yang, Q. Diep et al., Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury,, A. M. Tan, S. Stamboulian, Y. W. Chang et al., Neuropathic pain memory is maintained by Rac1-regulated dendritic spine remodeling after spinal cord injury,, F. Knerlich-Lukoschus, M. Juraschek, U. Blmer, R. Lucius, H. M. Mehdorn, and J. Held-Feindt, Force-dependent development of neuropathic central pain and time-related CCL2/CCR2 expression after graded spinal cord contusion injuries of the rat,, Y. Berrocal, D. D. Pearse, A. Singh et al., Social and environmental enrichment improves sensory and motor recovery after severe contusive spinal cord injury in the rat,, J. Biernaskie, J. S. Sparling, J. Liu et al., Skin-derived precursors generate myelinating Schwann cells that promote remyelination and functional recovery after contusion spinal cord injury,, M. G. Dombourian, N. A. Turner, T. A. Gerovac et al., B1 and TRPV-1 receptor genes and their relationship to hyperalgesia following spinal cord injury,, C. D. Mills, J. J. Grady, and C. E. Hulsebosch, Changes in exploratory behavior as a measure of chronic central pain following spinal cord injury,, C. H. Hubscher, J. D. Fell, and D. S. Gupta, Sex and hormonal variations in the development of at-level allodynia in a rat chronic spinal cord injury model,, C. H. Hubscher, E. G. Kaddumi, and R. D. Johnson, Segmental neuropathic pain does not develop in male rats with complete spinal transections,, J. Voda, A. Hama, and J. Sagen, FK506 reduces the severity of cutaneous hypersensitivity in rats with a spinal cord contusion,, B. C. Hains, J. P. Klein, C. Y. Saab, M. J. Craner, J. Treatment effectiveness in animals with SCI is often measured simply by whether or not independent ambulation has occurred. Because spasticity results in musculoskeletal pain, the spinal cord injury model could be considered a musculoskeletal pain model. However, more attention should be focused on motor recovery while evaluating pain behavior, because of the delayed motor recovery in mice compared with rats [32, 33]. These experimental findings indicate that the standardized experimental rat models of dorsal and ventral SCI may be stable, reliable, and reproducible. Following laminectomy, compression injury is induced with clips calibrated to exert a force of 50 or 35g. The 50-g clip induces severe injury and the 35-g clip induces moderate injury. Lozos et al. Ideal models should meet the following conditions (Akhtar et al., 2008): (1) simulate damage that is similar to clinical SCI; (2) be controlled, reproducible, and stable; (3) involve a simple technique that is easy to study; (4) the equipment used to make a model is straightforward and quick to produce. A. Moreover, genomic DNA variants could predict trait sensitivity to pain rather than ongoing levels of pain. Motor deficits are related to irradiation duration, as well as mechanical allodynia (cold, not thermal), which lasts for several days [91]. 1993;119:153164, 20. These studies have brought to light the pathophysiology of SCI and a growing number of novel treatments that promote behavioral recovery. Recently, these various SCI animal models have been utilized for pain studies [5]. Zheng YH, Fang Z, Cao P, Zheng T, Sun CH, Lu J, Shi RY. In one of the methods, the up-down method [109], each von Frey hair is applied to the test area for 2-3s, with a 1-2-minute interval between stimuli. Following application of the von Frey filament to the trunk, behavioral analysis is performed according to vocalization threshold. A cost-effective approach for an experimental SCI rat model has been to create a customized impact device (Vijayaprakash and Sridharan, 2013), which is a customized blunt-force impact device designed to induce a standard animal model of contusive SCI at the thoracic level. It is difficult to bilaterally drop the rod onto the spinal cord. 2004;7:372377, 28. Motoneuron and sensory neurons are often regulated by common mechanisms [127], and common molecular mechanisms could be responsible for below-level neuropathic pain and spasticity [18, 37]. Furthermore, common clinical pain conditions, such as back pain, are too polygenic to be effectively modeled and genetically understood. SCI animal models, including the contusive, compressive, tractive, photochemical-induced, inflammatory injury, and ischemia-reperfusion injury models have been mostly used for investigating the pathophysiology of SCI. Aya Nakae, Kunihiro Nakai, Kenji Yano, Ko Hosokawa, Masahiko Shibata, Takashi Mashimo, "The Animal Model of Spinal Cord Injury as an Experimental Pain Model", BioMed Research International, vol. However, individual function-imaging scans could provide a reliable and objective measurement of subjective pain perception [25]. The pain is often characterized as stabbing or stimulus-independent and is accompanied by allodynia [21, 22]. Basoglu H, Kurtoglu T, Cetin NK, Bilgin MD, Kiylioglu N. Assessment of, 6. Motor dysfunction appears only in the ipsilateral injured side and persists from 5 days to 4 weeks [64, 75]. Pathology correlates with increased sprouting of primary afferent c-fibers into the spinal cord. In basic pain research, pain is defined as neuropathic or nociceptive. Vaquero C, Arce N, Agudo J, Martinez R, Garjal C, Diago MV. 2012;97:288303. Spinal cord injury is associated with permanent disability and decreased life expectancy (Hartkopp et al., 1997). Gonzalez-Lara LE, Xu X, Hofstetrova K, Pniak A, Brown A, Foster PJ. Animal models in spinal cord injury: a review Rev Neurosci. Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury Neuroscience. Occasionally, to attach the two ends for regeneration, a sterile, gel foam is placed between the two resected spinal cord ends. For more information, please refer to our Privacy Policy. A typical pathology is reduced blood flow to the peripheral nerve, resulting in demyelination or axonal degeneration, depending on the magnitude of ischemic injury. Mechanical allodynia and thermal hyperalgesia are bilaterally observed in above-level and below-level cases [61, 7681]. [. Krishna V, Andrews H, Jin X, Yu J, Varma A, Wen X, Kindy M. A contusion model of severe spinal cord injury in rats J Vis Exp. Ischemic preconditioning to prevent lethal ischemic spinal cord injury in a swine model J Invest Surg. Keyword Highlighting
Only a small percentage of injuries, infections, or others causes that results in chronic pain syndrome actually develop chronic pain. Spinal blood flow plays a significant role in maintaining spinal function. Abnormal sensations due to mechanical, thermal, or cold stimuli are observed for several weeks or longer [32, 33, 3952], and all regions (at-, above-, below-level) of allodynia are analyzed [5356]. A. Bertelli and J.-C. Mira, Behavioral evaluating methods in the objective clinical assessment of motor function after experimental brachial plexus reconstruction in the rat,, Y. Liu, D. Kim, B. T. Himes et al., Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function,, A. 2010;113:880891, 5. Search for Similar Articles
According to studies published in flagship journals, pain studies comprise approximately 25% of total studies, more than any other field of study [27]. Read the winning articles. Wolters Kluwer Health
The level of SCI in completely transected animals has ranged from T6 to T13 with 47% between T9 and T11 (Battistuzzo et al., 2012). The biggest advantage of this method is that the resulting injury does not induce mechanical trauma to the cord, because there is no need for laminectomy. Review of basic and applied research Spine (Phila Pa 1976). Lumbar canal stenosis is due to entrapment of the cauda equine and/or lumber nerve roots by hypertrophy of osseous and soft tissue structures surrounding the lumbar spinal canal. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. Photochemically induced spinal cord injury in the rat Brain Res. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. 2011;197:97103, 36. to maintaining your privacy and will not share your personal information without
This method of inducing SCI may yield markedly different degrees of cord compression depending on the materials and apparatus. 1999;37:858861, 17. An additional scoring systems, described by Gale et al. Visceral pain usually exhibits a delayed onset following SCI, which could be due to normal afferent input via sympathetic or vagal nerves in paraplegics or via the vagus nerve in tetraplegics [19, 20]. Post-SCI pain results in drastically impaired daily routines and quality of life to a greater extent than motor impairment [11]; it is refractory to clinical treatments, despite a variety of neurosurgical, pharmacological, and behavioral therapeutic strategies [12, 13]. Scores are tabulated and considered to be an indicator of motor recovery. 
Ackery A, Tator C, Krassioukov A. Indeed, experiments with behavioral measurements of pain in animal models have become more common. SCI occurs in most countries at an annual rate of 2040 individuals per million. A. Ricci, E. Chee, D. Morganstein, and R. Lipton, Lost productive time and cost due to common pain conditions in the US workforce,, J. S. Richards, R. L. Meredith, C. Nepomuceno, P. R. Fine, and G. Bennett, Psycho-social aspects of chronic pain in spinal cord injury,, N. B. Finnerup, I. L. Johannesen, S. H. Sindrup, F. W. Bach, and T. S. Jensen, Pain and dysesthesia in patients with spinal cord injury: a postal survey,, P. J. Siddall, J. M. McClelland, S. B. Rutkowski, and M. J. Cousins, A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury,, D. H. Rintala, P. G. Loubser, J. Castro, K. A. Hart, and M. J. Fuhrer, Chronic pain in a community-based sample of men with spinal cord injury: prevalence, severity, and relationship with impairment, disability, handicap, and subjective well-being,, T. E. Balazy, Clinical management of chronic pain in spinal cord injury,, J. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. Three to five minutes are allowed between each trial, and three trials are averaged for each limb. Pickelsimer E, Shiroma EJ, Wilson DA. 2011;28:15891610, 21. spinal cord injury rat evaluation tissue strategies treatment engineering animal models t8 t10 segment vertebrae spine exposure t9 In addition, genetic biomarkers could prove to be useful. The effects of SCI are not limited to an individual's healthit also creates an enormous financial burden for families and society at large (Pickelsimer et al., 2010). The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury Prog Neurobiol. 2013;11:354359, 29. Therefore, especially in short distances from the rod to spinal cord, pain behavior does not always appear. [82], has proven to be one of the most reliable and reproducible graded experimental rat models of spinal cord injury [8394] and has been widely used to study neurotrauma in mice [88]. Possible explanations for the discrepancy may be due to the heterogeneity of human SCI and the challenging nature of measuring neurological function in clinical trial settings (Kwon et al., 2011). The present paper discussed the various SCI animal models as models for pain, with an emphasis on the complexities and limitations, as well as strategies for improvement and future use.
Ackery A, Tator C, Krassioukov A. Indeed, experiments with behavioral measurements of pain in animal models have become more common. SCI occurs in most countries at an annual rate of 2040 individuals per million. A. Ricci, E. Chee, D. Morganstein, and R. Lipton, Lost productive time and cost due to common pain conditions in the US workforce,, J. S. Richards, R. L. Meredith, C. Nepomuceno, P. R. Fine, and G. Bennett, Psycho-social aspects of chronic pain in spinal cord injury,, N. B. Finnerup, I. L. Johannesen, S. H. Sindrup, F. W. Bach, and T. S. Jensen, Pain and dysesthesia in patients with spinal cord injury: a postal survey,, P. J. Siddall, J. M. McClelland, S. B. Rutkowski, and M. J. Cousins, A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury,, D. H. Rintala, P. G. Loubser, J. Castro, K. A. Hart, and M. J. Fuhrer, Chronic pain in a community-based sample of men with spinal cord injury: prevalence, severity, and relationship with impairment, disability, handicap, and subjective well-being,, T. E. Balazy, Clinical management of chronic pain in spinal cord injury,, J. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. Three to five minutes are allowed between each trial, and three trials are averaged for each limb. Pickelsimer E, Shiroma EJ, Wilson DA. 2011;28:15891610, 21. spinal cord injury rat evaluation tissue strategies treatment engineering animal models t8 t10 segment vertebrae spine exposure t9 In addition, genetic biomarkers could prove to be useful. The effects of SCI are not limited to an individual's healthit also creates an enormous financial burden for families and society at large (Pickelsimer et al., 2010). The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury Prog Neurobiol. 2013;11:354359, 29. Therefore, especially in short distances from the rod to spinal cord, pain behavior does not always appear. [82], has proven to be one of the most reliable and reproducible graded experimental rat models of spinal cord injury [8394] and has been widely used to study neurotrauma in mice [88]. Possible explanations for the discrepancy may be due to the heterogeneity of human SCI and the challenging nature of measuring neurological function in clinical trial settings (Kwon et al., 2011). The present paper discussed the various SCI animal models as models for pain, with an emphasis on the complexities and limitations, as well as strategies for improvement and future use.
