Apoptosis is critical for triggering collateral damage following primary injury to the spinal cord. In addition, psychosocial aspects of chronic pain due to spinal cord injury have been completely omitted, despite a large body of knowledge emphasizing the importance of these factors in chronic pain. 
Methods to assess the development and recovery of locomotor function after spinal cord injury in rats Exp Neurol. (1991) developed a rat model of photochemical-induced SCI, in which female rats were intravenously injected with Erythrosin B and the T10 vertebra was irradiated with a laser beam for 1, 5 or 10 minutes. Spinal contusion is the oldest and most widely used animal model. In excitotoxic animal models, nearly 100% animals develop varying degrees of hypersensitivity to mechanical and thermal stimuli [98]. The pathology of human SCI is not greatly different from that of experimental animals, although important specific differences exist. your express consent. Therefore, this model could provide useful and novel insights into the underlying biological mechanisms of spinal cord injury [108]. Martinez, A simple, inexpensive and easily reproducible model of spinal cord injury in mice: morphological and functional assessment,, A. D. Kloos, L. C. Fisher, M. R. Detloff, D. L. Hassenzahl, and D. M. Basso, Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats,, L. B. Jakeman, Z. Guan, W. Ping et al., Traumatic spinal cord injury produced by controlled contusion in mouse,, T. Ito, S. Ohtori, G. Inoue et al., Glial phosphorylated p38 MAP kinase mediates pain in a rat model of lumbar disc herniation and induces motor dysfunction in a rat model of lumbar spinal canal stenosis,, M. Sekiguchi, S. Kikuchi, and R. R. Myers, Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain,, G. Wang and S. M. Thompson, Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions,, S. R. Chaplan, F. W. Bach, J. W. Pogrel, J. M. Chung, and T. L. Yaksh, Quantitative assessment of tactile allodynia in the rat paw,, T. L. Yaksh, Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists,, G. J. Bennett and Y. K. Xie, A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man,, Y. Choi, Y. W. Yoon, H. S. Na, S. H. Kim, and J. M. Chung, Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain,, D. M. Basso, L. C. Fisher, A. J. Anderson, L. B. Jakeman, D. M. McTigue, and P. G. Popovich, Basso mouse scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains,, M. Martinez, J. M. Brezun, L. Bonnier, and C. Xerri, A new rating scale for open-field evaluation of behavioral recovery after cervical spinal cord injury in rats,, J. 14. Functional outcomes commonly used in experimental animal SCI include histopathological and electrophysiological measures, spinal cord blood flow, the Basso Mouse scale (Yu et al., 2014), and measurement of biomarkers such as lipid peroxidation. Wang W, Yang T, Lei M, Pei F, Liu L. Establishment of tractive spinal cord injury model in rats with a novel spinal distractor Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. Therefore, in human studies, it will be difficult to determine the correlation between genetic background and pain severity. 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. 2004;21:429440, 31. Classification of the Spinal Cord Injury Pain Task Force of the International Association of the Study of Pain. A positive response is defined as a rapid withdrawal and/or licking of the paw immediately upon application of the stimulus. Over the past 30 years, there has been substantial worldwide research for establishing animal models, and a large number of therapeutic strategies have been developed (Kwon et al., 2011; Tetzlaff et al., 2011). Spasticity is a disabling complication that affects individuals with spinal cord injury [18, 120]. Histological, biochemical, and molecular techniques for assessing the outcome of SCI and/or its treatment have been well established. 1992;9:147149, 10. In complete and partial spinal lesions, chronic pain develops within months following injury [8]. II.Time limits for recovery after acute compression in dogs AMA Arch Neurol Psychiatry. In response to noxious stimuli, behaviors can be reliably and objectively scored, although these simple reflexes or innate responses (such as licking an inflamed paw) seem to lack clinical validity. Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury Neuroscience. Black, and S. G. Waxman, Upregulation of sodium channel Na1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury,, C. Scheifer, U. Hoheisel, P. Trudrung, T. Unger, and S. Mense, Rats with chronic spinal cord transection as a possible model for the at-level pain of paraplegic patients,, V. S. Densmore, A. Kalous, J. R. Keast, and P. B. Osborne, Above-level mechanical hyperalgesia in rats develops after incomplete spinal cord injury but not after cord transection, and is reversed by amitriptyline, morphine and gabapentin,, C. Crone, N. T. Petersen, S. Gimenz-Roldn, B. Lungholt, K. Nyborg, and J. Below-level pain is localized to dermatomes distal to the injury site and develops more gradually than at level pain; it is often classified as a stimulus-independent, continuous, burning pain [21, 22]. Nonetheless, the subjectivity of these measures has led to a decade-long search for surrogate biomarkers. 1999;37:858861, 17. It is crucial for a pain clinician to distinguish between nociceptive or neuropathic pain, because the clinical approach for each is different. However, by focusing on various symptoms of spinal cord injury pain, treatment possibilities for pathologies of spinal cord injury pain could emerge. Highlight selected keywords in the article text. Moreover, genomic DNA variants could predict trait sensitivity to pain rather than ongoing levels of pain. Yu CG, Singh R, Crowdus C, Raza K, Kincer J, Geddes JW. It results in varying degrees of paralysis, sensory loss, and bladder/bowel dysfunction. 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]. These include contusion impactors (Krishna et al., 2013) and clip compression (Alluin et al., 2011). Following application of the von Frey filament to the trunk, behavioral analysis is performed according to vocalization threshold. Spinal cord injury models: neurophysiology J Neurotrauma. Zhang, Ning1; Fang, Marong2; Chen, Haohao1; Gou, Fangming1; Ding, Mingxing1,2, 1Department of Medical Sciences, Jinhua Polytechnic, Jinhua, Zhejiang Province, China, 2Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. classified SCI pain by location of the pain [23]. In thoracic spinal cord injury, trunk allodynia reflects at-level neuropathic pain, and allodynia in the hindlimb reflects below-level neuropathic pain. However, clinical trials have, thus far, been uniformly disappointing. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. A. The impact of the injury tends to vary. Blight AR. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. A systematic review of cellular transplantation therapies for spinal cord injury J Neurotrauma. (2013) have reported that Aprikalim reduces the severity of ischemic SCI by 30 minutes of normothermic aortic cross-clamping in a rabbit model of spinal cord ischemia (Lozos et al., 2013). Standardizing laboratory procedures for different species and strains may also decrease the differences between normal and injured spinal cord biochemistry. 1976;44:429434, 18. This suggests that common mechanisms could underlie specific symptoms derived from various injury conditions. Photochemically induced spinal cord injury in the rat Brain Res. Significant scientific interest has been devoted to spasticity over the past 1015 years as an example of plastic changes occurring distal to a central lesion. 1954;71:271290, 40. 2011;36:E155163, 30. 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. However, at a more fundamental level, the differences in size, anatomy, and the pathophysiological responses to injury may quite possibly exist between SCI in rodents and in human patients. However, results can be easily misunderstood and falsely interpreted. Many studies have reported muscle spasms in the spinal complete transection model [18, 59, 60], and musculoskeletal pain pathology during spasticity could help to clarify the use of this model. Ischemic preconditioning to prevent lethal ischemic spinal cord injury in a swine model J Invest Surg. In chronic states, secondary overuse or abnormal use of structures, such as the arm and shoulder, occurs [17]. Spinal cord injury is associated with permanent disability and decreased life expectancy (Hartkopp et al., 1997). Sports-related SCI has also been discussed for diving athletes. Pickelsimer E, Shiroma EJ, Wilson DA. Over the past two decades, the photochemical model of spinal cord injury, developed by Watson et al. Objective clinical assessment of motor function after experimental spinal cord injury in the rat J Neurosurg. The von Frey hair can also be used to determine vocalization threshold to graded mechanical allodynia as a means to evaluate at-level neuropathic pain in the trunk [92]. Data is temporarily unavailable. To accurately evaluate ischemic injury of the spinal cord, endoprosthesis implantation in the thoraco-abdominal aorta has been used (Vaquero et al., 2007). Han Q, Jin W, Xiao Z, Ni H, Wang J, Kong J, Wu J, Liang W, Chen L, Zhao Y, Chen B, Dai J. (2004) used spines that were tracted longitudinally with a special spinal retractor that was put on the processus transversus vertebrae of the rat after exposing the spinal cord to dual laminectomy. In brief, the exposed spinal cord is injured by dropping a 10.0-g rod from specified heights [37, 38]. Such animal models have been established via transient aortic occlusion by cross-clamping the descending aorta through a lateral thoracotomy (Awad et al., 2010). 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). Min SH, Lee SH, Shim H, Park JS, Lee YI, Kim HW, Hyun JK. 2010;33:221231, 34. For information on cookies and how you can disable them visit our Privacy and Cookie Policy. Experimental SCI is induced by dropping calibrated weights through a vented tube onto a small impounder resting on the surgically exposed cord (Koozekanani et al., 1976). No related content is available yet for this article. Awad H, Ankeny DP, Guan Z, Wei P, McTigue DM, Popovich PG. Basoglu H, Kurtoglu T, Cetin NK, Bilgin MD, Kiylioglu N. Assessment of, 6. 2013;4:57, 44. Some approaches to the standardization of this injury model have been suggested (Yeo et al., 2004). Yeo SJ, Hwang SN, Park SW, Kim YB, Min BK, Kwon JT, Suk JS. Three to five minutes are allowed between each trial, and three trials are averaged for each limb. A. Turner, D. D. Cardenas, C. A. Warms, and C. B. McClellan, Chronic pain associated with spinal cord injuries: a community survey,, D. M. Cairns, R. H. Adkins, and M. D. Scott, Pain and depression in acute traumatic spinal cord injury: origins of chronic problematic pain?, M. Segatore, Understanding chronic pain after spinal cord injury,, P. J. Siddall, R. P. Yezierski, and J. D. Loeser, Pain following spinal cord injury: clinical features, prevalence, and taxonomy,, M. Dalyan, D. D. Cardenas, and B. Gerard, Upper extremity pain after spinal cord injury,, K. C. Murray, A. Nakae, M. J. Stephens et al., Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT receptors,, B. R. Komisaruk, C. A. Gerdes, and B. Whipple, 'Complete' spinal cord injury does not block perceptual responses to genital self-stimulation in women,, R. A. Kuhn, Functional capacity of the isolated human spinal cord,, P. J. Siddall, R. P. Yezierski, and J. D. Loeser, Taxonomy and epidemiology of spinal cord injury pain, in, C. J. Vierck Jr. and A. R. Light, Allodynia and hyperalgesia within dermatomes caudal to a spinal cord injury in primates and rodents, in, T. N. Bryce, M. P. J. M. Dijkers, K. T. Ragnarsson, A. Please try again soon. However, these procedures also induce mechanical hypoalgesia [107]. Kwon BK, Okon EB, Plunet W, Baptiste D, Fouad K, Hillyer J, Weaver LC, Fehlings MG, Tetzlaff W. A systematic review of directly applied biologic therapies for acute spinal cord injury J Neurotrauma. 1993;119:153164, 20. Above-level pain occurs at dermatomes cranial to the injury site [21, 22]. Both the Tarlov and inclined plane tests assess general locomotor ability and do not reflect specific changes in motor or sensory function (Kunkel-Bagden et al., 1993). Lafci G, Gedik HS, Korkmaz K, Erdem H, Cicek OF, Nacar OA, Yildirim L, Kaya E, Ankarali H. Efficacy of iloprost and montelukast combination on spinal cord ischemia/reperfusion injury in a rat model J Cardiothorac Surg. The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury Prog Neurobiol. Prior to embarking on lengthy and expensive clinical trials, an animal SCI model that is an intermediary between both a rodent and human SCI may be a valuable translational research resource for pre-clinically evaluating novel therapies (Nout et al., 2012; Zurita et al., 2012; Lee et al., 2013). Spontaneous and evoked pain is frequent in traumatic or ischemic spinal cord injury. Despite these well recognized advantages, the SCI research community has also acknowledged the frustrating reality that even after the studies from these rodent models, clinical trials have failed to demonstrate convincing efficacy (Tator, 2006). These studies have primarily focused on spinal cord injury caused by contusion or weight dropping, spinal cord compression, excitatory neurotoxins, photochemical-induced ischemia, spinal cord transaction, or crushing of the spinal cord. Furthermore, ischemia/reperfusion injury may directly or indirectly be responsible for aortic cross-clamping, and may result in severe postoperative complications caused by SCI (Lafci et al., 2013). 2000;17:317324, 39. In human SCI, trauma severity is not proportional to pain severity, because the method of injury varies. Overall, we can conclude that accurate measurement of fine motor and sensory function in animals, especially in rodents, is quite difficult. However, based on the above-described mechanisms, a morphological approach to spinal complete transection injury has been utilized [128]. Following cervical spinal cord injury, recovery of forelimb function can be measured [114] by indicators such as the grooming test and forelimb asymmetry test [115]. Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK. Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia Int J Surg. Pain experiments with human subjects have proven to be practically challenging, fundamentally subjective, and ethically self-limiting. The light beam is automatically turned off by a photocell upon limb-lift, allowing for measurement of time between stimulus start and paw withdrawal (paw withdrawal latency). A number of animal models of SCI exist and are primarily used to determine mechanisms of motor dysfunctions [24]. Lee et al. However, in experimental animals, these injuries are most frequently induced dorsally and in the thoracic spine, whereas most clinical injuries occur anteriorly and in the cervical region (Akhtar et al., 2008). Neural Regeneration Research9(22):2008-2012, November 15, 2014. For example, some animal studies benefit from the treatment of acute SCI. Many spinal cord injury models exist for pain research. Locomotor function is observed and recorded using the Basso, Beattie, and Bresnahan (BBB) Locomotor Rating Scale [95]. A systematic review of exercise training to promote locomotor recovery in animal models of spinal cord injury J Neurotrauma. Basso DM, Beattie MS, Bresnahan JC. This results in gradual increases in the degree of histopathological injury leading to decreased Tarlov and BBB scores for the behavioral test and increased Ashworth scores for the hind limb. These include the Basso, Beattie, Bresnahan (BBB), the locomotor scale (Zeman et al., 2008), the cylinder rearing test (Lee et al., 2010), the horizontal ladder test (Lee et al., 2010), and the catwalk (Van Meeteren et al., 2003). Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. In addition, forelimb motor function recovery and pain behavior should be coanalyzed, because behavior is a result of motor functions [118]. 2011;28:19631981, 4. These models have also been adapted for mice [2831]. Article of the Year Award: Outstanding research contributions of 2021, as selected by our Chief Editors. 2014;7:28, 27. 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. Implantation of scaffolding biomaterials is applicable to this kind of SCI model, and these biomaterials provide effective bridging and stimulating effects on neural regeneration and prevent the formation of glial scars in the completely transected SCI rat models (Han et al., 2010). Nevertheless, this model could help to clarify pathophysiology of chronic, light pressure to the spinal cord. Future studies should extend the scope of inquiry to include the psychosocial aspects of chronic pain and spinal cord injury. Mechanical allodynia can be measured in various ways using the von Frey hair. 2004;21:13551370, 2. Patients with upper thoracic injury or cervical SCI may present with autonomic dysreflexia headache, because of bowel impaction or bladder distension. 2012;29:16001613, 8. B. Nielsen, and K. Klinge, Spasticity-assessment: a review,, F. M. Maynard, R. S. Karunas, and W. P. Waring III, Epidemiology of spasticity following traumatic spinal cord injury,, P. Boulenguez and L. Vinay, Strategies to restore motor functions after spinal cord injury,, Y. Li, M. A. Gorassini, and D. J. Bennett, Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats,, R. Katz, Presynaptic inhibition in humans: a comparison between normal and spastic patients,, G. I. Boorman, R. G. Lee, W. J. Becker, and U. R. Windhorst, Impaired "natural reciprocal inhibition" in patients with spasticity due to incomplete spinal cord injury,, P. Boulenguez, S. Liabeuf, R. Bos et al., Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury,, S. Hou, H. Duale, and A. G. Rabchevsky, Intraspinal sprouting of unmyelinated pelvic afferents after complete spinal cord injury is correlated with autonomic dysreflexia induced by visceral pain,. Following mechanical injury to the spinal cord, a wave of secondary pathological changes occurs and amplifies the extent of initial damage. Combined Behavioral Score (CBS), as reported by Gale et al. Following excitotoxin injections, neuronal loss, cavity formation, astrocytic scaring, and prominent inflammation occur. Thermal hyperalgesia can be measured by latency of paw withdrawal in response to a radiant heat source [111]. B. Nielsen, Reduced reciprocal inhibition is seen only in spastic limbs in patients with neurolathyrism,, S. A. Edgley and N. C. Aggelopoulos, Short latency crossed inhibitory reflex actions evoked from cutaneous afferents,, A. D. Bennett, A. W. Everhart, and C. E. Hulsebosch, Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury,, M. D. Christensen, A. W. Everhart, J. T. Pickelman, and C. E. Hulsebosch, Mechanical and thermal allodynia in chronic central pain following spinal cord injury,, B. C. Hains, K. M. Chastain, A. W. Everhart, D. J. McAdoo, and C. E. Hulsebosch, Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb allodynia in a rodent model of chronic central pain after spinal cord hemisection injury,, M. F. Coronel, F. Labombarda, M. J. Villar, A. F. De Nicola, and S. L. Gonzlez, Progesterone prevents allodynia after experimental spinal cord injury,, D. H. Roh, S. Y. Yoon, H. S. Seo et al., Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats,, J. Kim, J. H. Kim, Y. Kim, H. Y. Cho, S. K. Hong, and Y. W. Yoon, Role of spinal cholecystokinin in neuropathic pain after spinal cord hemisection in rats,, Y. S. Gwak and C. E. Hulsebosch, Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat,, F. Marchand, C. Tsantoulas, D. Singh et al., Effects of Etanercept and Minocycline in a rat model of spinal cord injury,, Y. Lu, J. Zheng, L. Xiong, M. Zimmermann, and J. Yang, Spinal cord injury-induced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat,, F. Labombarda, M. F. Coronel, M. J. Villar, A. F. D. Nicola, and S. L. Gonzlez, Neuropathic pain and temporal expression of preprodynorphin, protein kinase C and N-methyl-d-aspartate receptor subunits after spinal cord injury,, W. Liu, Z. Liu, LI. A great effort has been made to develop assessment scales and procedures to appropriately measure functional outcomes. A long-term epidemiological survey from Denmark Spinal Cord. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 2009;46:479483, 33. 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. Ackery A, Tator C, Krassioukov A. 2013;8:64, 23. Similar alterations have been observed in the ventral SCI rats proportional to the increase in compression weight (Zheng et al., 2012). Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. Animal models cannot self-report. 1994;127:7693, 11. de la Torre JC. Contusive SCI models: To establish an experimental animal model of contusive SCI, a pneumatic impact device was made in Korea to induce a contusive injury on the dorsal spinal cord (Yeo et al., 2004). Pathology correlates with increased sprouting of primary afferent c-fibers into the spinal cord. 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]. 2004;19:574580, 50. Koozekanani SH, Vise WM, Hashemi RM, McGhee RB. For more information, please refer to our Privacy Policy. Kunkel-Bagden E, Dai HN, Bregman BS. 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]. 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. Scores from 0 to 7 rank early phase of recovery, with return of isolated movements from three joints (hip, knee, and ankle); scores from 8 to 13 describe the intermediate recovery phase with, return of paw placement, stepping, and forelimb-hindlimb coordination; and scores from 14 to 21 represent late phase of recovery, with return of toe clearance during the step phase, predominant paw position, trunk stability, and tail position. These studies have brought to light the pathophysiology of SCI and a growing number of novel treatments that promote behavioral recovery. 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, . 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. Locomotor recovery after spinal cord contusion injury in rats is improved by spontaneous exercise J Neurotrauma. Most methods of recording evoked potentials involve craniotomy and laminectomy for electrode placement, which allow for only single acute measurements (Sun et al., 2000). The promotion of, 15. As the economic development all over the world, spinal cord injury (SCI) occurs with an annual incidence of 12.157.8 cases per million (van den Berg et al., 2010). Some error has occurred while processing your request. Animal models in spinal cord injury: a review Rev Neurosci. Moreover, the percentage of animals that exhibit pain-related behaviors following injury is greater than with other models; induced mechanical allodynia was 67% in the contusion injury model [99], in contrast to 44% chronic allodynia following ischemic injury [86]. If SCI pain could be eliminated, the quality of life could be greatly improved in patients; they would no longer suffer from pain and could take part in social aspects of life or earn money. 2008;63:981987987-988, 52. The utility for each model summarizes in Table 3. A. Webb and G. D. Muir, Sensorimotor behaviour following incomplete cervical spinal cord injury in the rat,, J. F. Ditunno, J. W. Little, A. Tessler, and A. S. Burns, Spinal shock revisited: a four-phase model,, F. Biering-Srensen, J. Scores are tabulated and considered to be an indicator of motor recovery. These endpoint measurements produce interpretable and comparable results between studies. The number of brisk foot withdrawals is recorded. Li XQ, Wang J, Fang B, Tan WF, Ma H. Intrathecal antagonism of microglial TLR4 reduces inflammatory damage to blood-spinal cord barrier following ischemia/reperfusion injury in rats Mol Brain. Pain behavior should not be measured in injured animals during maximal motor dysfunction. 2012;92:15911595, 53. Stereotactic radiosurgery improves locomotor recovery after spinal cord injury in rats Neurosurgery. These patients typically cannot only walk, but also lose bowel, bladder, and sexual functions. 2010;34:184192 192, 43. van Gorp S, Leerink M, Kakinohana O, Platoshyn O, Santucci C, Galik J, Joosten EA, Hruska-Plochan M, Goldberg D, Marsala S, Johe K, Ciacci JD, Marsala M. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation Stem Cell Res Ther. The tractive SCI model is a reliable animal model for studying pathological mechanisms and treatment of tractive SCI (Wang et al., 2011). The unique features of controlled displacement and monitoring of biomechanical parameters at the time of impact help to reduce outcome variability [105]. Spinal cord injury. Motor and sensory dysfunction has been periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds, and myogenic motor evoked potentials. Treatment effectiveness in animals with SCI is often measured simply by whether or not independent ambulation has occurred. A typical pathology is reduced blood flow to the peripheral nerve, resulting in demyelination or axonal degeneration, depending on the magnitude of ischemic injury. The animal skin is briskly stroked with a pencil point in a rostral to caudal direction. These features resemble allodynia and hyperalgesia experienced by humans suffering from central pain syndromes following spinal cord injury. Zheng YH, Fang Z, Cao P, Zheng T, Sun CH, Lu J, Shi RY. 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. 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). Touch-evoked agitation is another evaluation of mechanical allodynia [110] and can be used to test the animal response to tactile stimulation.
Methods to assess the development and recovery of locomotor function after spinal cord injury in rats Exp Neurol. (1991) developed a rat model of photochemical-induced SCI, in which female rats were intravenously injected with Erythrosin B and the T10 vertebra was irradiated with a laser beam for 1, 5 or 10 minutes. Spinal contusion is the oldest and most widely used animal model. In excitotoxic animal models, nearly 100% animals develop varying degrees of hypersensitivity to mechanical and thermal stimuli [98]. The pathology of human SCI is not greatly different from that of experimental animals, although important specific differences exist. your express consent. Therefore, this model could provide useful and novel insights into the underlying biological mechanisms of spinal cord injury [108]. Martinez, A simple, inexpensive and easily reproducible model of spinal cord injury in mice: morphological and functional assessment,, A. D. Kloos, L. C. Fisher, M. R. Detloff, D. L. Hassenzahl, and D. M. Basso, Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats,, L. B. Jakeman, Z. Guan, W. Ping et al., Traumatic spinal cord injury produced by controlled contusion in mouse,, T. Ito, S. Ohtori, G. Inoue et al., Glial phosphorylated p38 MAP kinase mediates pain in a rat model of lumbar disc herniation and induces motor dysfunction in a rat model of lumbar spinal canal stenosis,, M. Sekiguchi, S. Kikuchi, and R. R. Myers, Experimental spinal stenosis: relationship between degree of cauda equina compression, neuropathology, and pain,, G. Wang and S. M. Thompson, Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions,, S. R. Chaplan, F. W. Bach, J. W. Pogrel, J. M. Chung, and T. L. Yaksh, Quantitative assessment of tactile allodynia in the rat paw,, T. L. Yaksh, Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists,, G. J. Bennett and Y. K. Xie, A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man,, Y. Choi, Y. W. Yoon, H. S. Na, S. H. Kim, and J. M. Chung, Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain,, D. M. Basso, L. C. Fisher, A. J. Anderson, L. B. Jakeman, D. M. McTigue, and P. G. Popovich, Basso mouse scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains,, M. Martinez, J. M. Brezun, L. Bonnier, and C. Xerri, A new rating scale for open-field evaluation of behavioral recovery after cervical spinal cord injury in rats,, J. 14. Functional outcomes commonly used in experimental animal SCI include histopathological and electrophysiological measures, spinal cord blood flow, the Basso Mouse scale (Yu et al., 2014), and measurement of biomarkers such as lipid peroxidation. Wang W, Yang T, Lei M, Pei F, Liu L. Establishment of tractive spinal cord injury model in rats with a novel spinal distractor Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. Therefore, in human studies, it will be difficult to determine the correlation between genetic background and pain severity. 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. 2004;21:429440, 31. Classification of the Spinal Cord Injury Pain Task Force of the International Association of the Study of Pain. A positive response is defined as a rapid withdrawal and/or licking of the paw immediately upon application of the stimulus. Over the past 30 years, there has been substantial worldwide research for establishing animal models, and a large number of therapeutic strategies have been developed (Kwon et al., 2011; Tetzlaff et al., 2011). Spasticity is a disabling complication that affects individuals with spinal cord injury [18, 120]. Histological, biochemical, and molecular techniques for assessing the outcome of SCI and/or its treatment have been well established. 1992;9:147149, 10. In complete and partial spinal lesions, chronic pain develops within months following injury [8]. II.Time limits for recovery after acute compression in dogs AMA Arch Neurol Psychiatry. In response to noxious stimuli, behaviors can be reliably and objectively scored, although these simple reflexes or innate responses (such as licking an inflamed paw) seem to lack clinical validity. Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury Neuroscience. Black, and S. G. Waxman, Upregulation of sodium channel Na1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury,, C. Scheifer, U. Hoheisel, P. Trudrung, T. Unger, and S. Mense, Rats with chronic spinal cord transection as a possible model for the at-level pain of paraplegic patients,, V. S. Densmore, A. Kalous, J. R. Keast, and P. B. Osborne, Above-level mechanical hyperalgesia in rats develops after incomplete spinal cord injury but not after cord transection, and is reversed by amitriptyline, morphine and gabapentin,, C. Crone, N. T. Petersen, S. Gimenz-Roldn, B. Lungholt, K. Nyborg, and J. Below-level pain is localized to dermatomes distal to the injury site and develops more gradually than at level pain; it is often classified as a stimulus-independent, continuous, burning pain [21, 22]. Nonetheless, the subjectivity of these measures has led to a decade-long search for surrogate biomarkers. 1999;37:858861, 17. It is crucial for a pain clinician to distinguish between nociceptive or neuropathic pain, because the clinical approach for each is different. However, by focusing on various symptoms of spinal cord injury pain, treatment possibilities for pathologies of spinal cord injury pain could emerge. Highlight selected keywords in the article text. Moreover, genomic DNA variants could predict trait sensitivity to pain rather than ongoing levels of pain. Yu CG, Singh R, Crowdus C, Raza K, Kincer J, Geddes JW. It results in varying degrees of paralysis, sensory loss, and bladder/bowel dysfunction. 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]. These include contusion impactors (Krishna et al., 2013) and clip compression (Alluin et al., 2011). Following application of the von Frey filament to the trunk, behavioral analysis is performed according to vocalization threshold. Spinal cord injury models: neurophysiology J Neurotrauma. Zhang, Ning1; Fang, Marong2; Chen, Haohao1; Gou, Fangming1; Ding, Mingxing1,2, 1Department of Medical Sciences, Jinhua Polytechnic, Jinhua, Zhejiang Province, China, 2Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. classified SCI pain by location of the pain [23]. In thoracic spinal cord injury, trunk allodynia reflects at-level neuropathic pain, and allodynia in the hindlimb reflects below-level neuropathic pain. However, clinical trials have, thus far, been uniformly disappointing. In this article, we systematically review and analyze various kinds of animal models of spinal cord injury and assess their advantages and disadvantages for further studies. A. The impact of the injury tends to vary. Blight AR. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. A systematic review of cellular transplantation therapies for spinal cord injury J Neurotrauma. (2013) have reported that Aprikalim reduces the severity of ischemic SCI by 30 minutes of normothermic aortic cross-clamping in a rabbit model of spinal cord ischemia (Lozos et al., 2013). Standardizing laboratory procedures for different species and strains may also decrease the differences between normal and injured spinal cord biochemistry. 1976;44:429434, 18. This suggests that common mechanisms could underlie specific symptoms derived from various injury conditions. Photochemically induced spinal cord injury in the rat Brain Res. Significant scientific interest has been devoted to spasticity over the past 1015 years as an example of plastic changes occurring distal to a central lesion. 1954;71:271290, 40. 2011;36:E155163, 30. 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. However, at a more fundamental level, the differences in size, anatomy, and the pathophysiological responses to injury may quite possibly exist between SCI in rodents and in human patients. However, results can be easily misunderstood and falsely interpreted. Many studies have reported muscle spasms in the spinal complete transection model [18, 59, 60], and musculoskeletal pain pathology during spasticity could help to clarify the use of this model. Ischemic preconditioning to prevent lethal ischemic spinal cord injury in a swine model J Invest Surg. In chronic states, secondary overuse or abnormal use of structures, such as the arm and shoulder, occurs [17]. Spinal cord injury is associated with permanent disability and decreased life expectancy (Hartkopp et al., 1997). Sports-related SCI has also been discussed for diving athletes. Pickelsimer E, Shiroma EJ, Wilson DA. Over the past two decades, the photochemical model of spinal cord injury, developed by Watson et al. Objective clinical assessment of motor function after experimental spinal cord injury in the rat J Neurosurg. The von Frey hair can also be used to determine vocalization threshold to graded mechanical allodynia as a means to evaluate at-level neuropathic pain in the trunk [92]. Data is temporarily unavailable. To accurately evaluate ischemic injury of the spinal cord, endoprosthesis implantation in the thoraco-abdominal aorta has been used (Vaquero et al., 2007). Han Q, Jin W, Xiao Z, Ni H, Wang J, Kong J, Wu J, Liang W, Chen L, Zhao Y, Chen B, Dai J. (2004) used spines that were tracted longitudinally with a special spinal retractor that was put on the processus transversus vertebrae of the rat after exposing the spinal cord to dual laminectomy. In brief, the exposed spinal cord is injured by dropping a 10.0-g rod from specified heights [37, 38]. Such animal models have been established via transient aortic occlusion by cross-clamping the descending aorta through a lateral thoracotomy (Awad et al., 2010). 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). Min SH, Lee SH, Shim H, Park JS, Lee YI, Kim HW, Hyun JK. 2010;33:221231, 34. For information on cookies and how you can disable them visit our Privacy and Cookie Policy. Experimental SCI is induced by dropping calibrated weights through a vented tube onto a small impounder resting on the surgically exposed cord (Koozekanani et al., 1976). No related content is available yet for this article. Awad H, Ankeny DP, Guan Z, Wei P, McTigue DM, Popovich PG. Basoglu H, Kurtoglu T, Cetin NK, Bilgin MD, Kiylioglu N. Assessment of, 6. 2013;4:57, 44. Some approaches to the standardization of this injury model have been suggested (Yeo et al., 2004). Yeo SJ, Hwang SN, Park SW, Kim YB, Min BK, Kwon JT, Suk JS. Three to five minutes are allowed between each trial, and three trials are averaged for each limb. A. Turner, D. D. Cardenas, C. A. Warms, and C. B. McClellan, Chronic pain associated with spinal cord injuries: a community survey,, D. M. Cairns, R. H. Adkins, and M. D. Scott, Pain and depression in acute traumatic spinal cord injury: origins of chronic problematic pain?, M. Segatore, Understanding chronic pain after spinal cord injury,, P. J. Siddall, R. P. Yezierski, and J. D. Loeser, Pain following spinal cord injury: clinical features, prevalence, and taxonomy,, M. Dalyan, D. D. Cardenas, and B. Gerard, Upper extremity pain after spinal cord injury,, K. C. Murray, A. Nakae, M. J. Stephens et al., Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT receptors,, B. R. Komisaruk, C. A. Gerdes, and B. Whipple, 'Complete' spinal cord injury does not block perceptual responses to genital self-stimulation in women,, R. A. Kuhn, Functional capacity of the isolated human spinal cord,, P. J. Siddall, R. P. Yezierski, and J. D. Loeser, Taxonomy and epidemiology of spinal cord injury pain, in, C. J. Vierck Jr. and A. R. Light, Allodynia and hyperalgesia within dermatomes caudal to a spinal cord injury in primates and rodents, in, T. N. Bryce, M. P. J. M. Dijkers, K. T. Ragnarsson, A. Please try again soon. However, these procedures also induce mechanical hypoalgesia [107]. Kwon BK, Okon EB, Plunet W, Baptiste D, Fouad K, Hillyer J, Weaver LC, Fehlings MG, Tetzlaff W. A systematic review of directly applied biologic therapies for acute spinal cord injury J Neurotrauma. 1993;119:153164, 20. Above-level pain occurs at dermatomes cranial to the injury site [21, 22]. Both the Tarlov and inclined plane tests assess general locomotor ability and do not reflect specific changes in motor or sensory function (Kunkel-Bagden et al., 1993). Lafci G, Gedik HS, Korkmaz K, Erdem H, Cicek OF, Nacar OA, Yildirim L, Kaya E, Ankarali H. Efficacy of iloprost and montelukast combination on spinal cord ischemia/reperfusion injury in a rat model J Cardiothorac Surg. The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury Prog Neurobiol. Prior to embarking on lengthy and expensive clinical trials, an animal SCI model that is an intermediary between both a rodent and human SCI may be a valuable translational research resource for pre-clinically evaluating novel therapies (Nout et al., 2012; Zurita et al., 2012; Lee et al., 2013). Spontaneous and evoked pain is frequent in traumatic or ischemic spinal cord injury. Despite these well recognized advantages, the SCI research community has also acknowledged the frustrating reality that even after the studies from these rodent models, clinical trials have failed to demonstrate convincing efficacy (Tator, 2006). These studies have primarily focused on spinal cord injury caused by contusion or weight dropping, spinal cord compression, excitatory neurotoxins, photochemical-induced ischemia, spinal cord transaction, or crushing of the spinal cord. Furthermore, ischemia/reperfusion injury may directly or indirectly be responsible for aortic cross-clamping, and may result in severe postoperative complications caused by SCI (Lafci et al., 2013). 2000;17:317324, 39. In human SCI, trauma severity is not proportional to pain severity, because the method of injury varies. Overall, we can conclude that accurate measurement of fine motor and sensory function in animals, especially in rodents, is quite difficult. However, based on the above-described mechanisms, a morphological approach to spinal complete transection injury has been utilized [128]. Following cervical spinal cord injury, recovery of forelimb function can be measured [114] by indicators such as the grooming test and forelimb asymmetry test [115]. Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK. Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia Int J Surg. Pain experiments with human subjects have proven to be practically challenging, fundamentally subjective, and ethically self-limiting. The light beam is automatically turned off by a photocell upon limb-lift, allowing for measurement of time between stimulus start and paw withdrawal (paw withdrawal latency). A number of animal models of SCI exist and are primarily used to determine mechanisms of motor dysfunctions [24]. Lee et al. However, in experimental animals, these injuries are most frequently induced dorsally and in the thoracic spine, whereas most clinical injuries occur anteriorly and in the cervical region (Akhtar et al., 2008). Neural Regeneration Research9(22):2008-2012, November 15, 2014. For example, some animal studies benefit from the treatment of acute SCI. Many spinal cord injury models exist for pain research. Locomotor function is observed and recorded using the Basso, Beattie, and Bresnahan (BBB) Locomotor Rating Scale [95]. A systematic review of exercise training to promote locomotor recovery in animal models of spinal cord injury J Neurotrauma. Basso DM, Beattie MS, Bresnahan JC. This results in gradual increases in the degree of histopathological injury leading to decreased Tarlov and BBB scores for the behavioral test and increased Ashworth scores for the hind limb. These include the Basso, Beattie, Bresnahan (BBB), the locomotor scale (Zeman et al., 2008), the cylinder rearing test (Lee et al., 2010), the horizontal ladder test (Lee et al., 2010), and the catwalk (Van Meeteren et al., 2003). Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. In addition, forelimb motor function recovery and pain behavior should be coanalyzed, because behavior is a result of motor functions [118]. 2011;28:19631981, 4. These models have also been adapted for mice [2831]. Article of the Year Award: Outstanding research contributions of 2021, as selected by our Chief Editors. 2014;7:28, 27. 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. Implantation of scaffolding biomaterials is applicable to this kind of SCI model, and these biomaterials provide effective bridging and stimulating effects on neural regeneration and prevent the formation of glial scars in the completely transected SCI rat models (Han et al., 2010). Nevertheless, this model could help to clarify pathophysiology of chronic, light pressure to the spinal cord. Future studies should extend the scope of inquiry to include the psychosocial aspects of chronic pain and spinal cord injury. Mechanical allodynia can be measured in various ways using the von Frey hair. 2004;21:13551370, 2. Patients with upper thoracic injury or cervical SCI may present with autonomic dysreflexia headache, because of bowel impaction or bladder distension. 2012;29:16001613, 8. B. Nielsen, and K. Klinge, Spasticity-assessment: a review,, F. M. Maynard, R. S. Karunas, and W. P. Waring III, Epidemiology of spasticity following traumatic spinal cord injury,, P. Boulenguez and L. Vinay, Strategies to restore motor functions after spinal cord injury,, Y. Li, M. A. Gorassini, and D. J. Bennett, Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats,, R. Katz, Presynaptic inhibition in humans: a comparison between normal and spastic patients,, G. I. Boorman, R. G. Lee, W. J. Becker, and U. R. Windhorst, Impaired "natural reciprocal inhibition" in patients with spasticity due to incomplete spinal cord injury,, P. Boulenguez, S. Liabeuf, R. Bos et al., Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury,, S. Hou, H. Duale, and A. G. Rabchevsky, Intraspinal sprouting of unmyelinated pelvic afferents after complete spinal cord injury is correlated with autonomic dysreflexia induced by visceral pain,. Following mechanical injury to the spinal cord, a wave of secondary pathological changes occurs and amplifies the extent of initial damage. Combined Behavioral Score (CBS), as reported by Gale et al. Following excitotoxin injections, neuronal loss, cavity formation, astrocytic scaring, and prominent inflammation occur. Thermal hyperalgesia can be measured by latency of paw withdrawal in response to a radiant heat source [111]. B. Nielsen, Reduced reciprocal inhibition is seen only in spastic limbs in patients with neurolathyrism,, S. A. Edgley and N. C. Aggelopoulos, Short latency crossed inhibitory reflex actions evoked from cutaneous afferents,, A. D. Bennett, A. W. Everhart, and C. E. Hulsebosch, Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury,, M. D. Christensen, A. W. Everhart, J. T. Pickelman, and C. E. Hulsebosch, Mechanical and thermal allodynia in chronic central pain following spinal cord injury,, B. C. Hains, K. M. Chastain, A. W. Everhart, D. J. McAdoo, and C. E. Hulsebosch, Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb allodynia in a rodent model of chronic central pain after spinal cord hemisection injury,, M. F. Coronel, F. Labombarda, M. J. Villar, A. F. De Nicola, and S. L. Gonzlez, Progesterone prevents allodynia after experimental spinal cord injury,, D. H. Roh, S. Y. Yoon, H. S. Seo et al., Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats,, J. Kim, J. H. Kim, Y. Kim, H. Y. Cho, S. K. Hong, and Y. W. Yoon, Role of spinal cholecystokinin in neuropathic pain after spinal cord hemisection in rats,, Y. S. Gwak and C. E. Hulsebosch, Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat,, F. Marchand, C. Tsantoulas, D. Singh et al., Effects of Etanercept and Minocycline in a rat model of spinal cord injury,, Y. Lu, J. Zheng, L. Xiong, M. Zimmermann, and J. Yang, Spinal cord injury-induced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat,, F. Labombarda, M. F. Coronel, M. J. Villar, A. F. D. Nicola, and S. L. Gonzlez, Neuropathic pain and temporal expression of preprodynorphin, protein kinase C and N-methyl-d-aspartate receptor subunits after spinal cord injury,, W. Liu, Z. Liu, LI. A great effort has been made to develop assessment scales and procedures to appropriately measure functional outcomes. A long-term epidemiological survey from Denmark Spinal Cord. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 2009;46:479483, 33. 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. Ackery A, Tator C, Krassioukov A. 2013;8:64, 23. Similar alterations have been observed in the ventral SCI rats proportional to the increase in compression weight (Zheng et al., 2012). Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. Animal models cannot self-report. 1994;127:7693, 11. de la Torre JC. Contusive SCI models: To establish an experimental animal model of contusive SCI, a pneumatic impact device was made in Korea to induce a contusive injury on the dorsal spinal cord (Yeo et al., 2004). Pathology correlates with increased sprouting of primary afferent c-fibers into the spinal cord. 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]. 2004;19:574580, 50. Koozekanani SH, Vise WM, Hashemi RM, McGhee RB. For more information, please refer to our Privacy Policy. Kunkel-Bagden E, Dai HN, Bregman BS. 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]. 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. Scores from 0 to 7 rank early phase of recovery, with return of isolated movements from three joints (hip, knee, and ankle); scores from 8 to 13 describe the intermediate recovery phase with, return of paw placement, stepping, and forelimb-hindlimb coordination; and scores from 14 to 21 represent late phase of recovery, with return of toe clearance during the step phase, predominant paw position, trunk stability, and tail position. These studies have brought to light the pathophysiology of SCI and a growing number of novel treatments that promote behavioral recovery. 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, . 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. Locomotor recovery after spinal cord contusion injury in rats is improved by spontaneous exercise J Neurotrauma. Most methods of recording evoked potentials involve craniotomy and laminectomy for electrode placement, which allow for only single acute measurements (Sun et al., 2000). The promotion of, 15. As the economic development all over the world, spinal cord injury (SCI) occurs with an annual incidence of 12.157.8 cases per million (van den Berg et al., 2010). Some error has occurred while processing your request. Animal models in spinal cord injury: a review Rev Neurosci. Moreover, the percentage of animals that exhibit pain-related behaviors following injury is greater than with other models; induced mechanical allodynia was 67% in the contusion injury model [99], in contrast to 44% chronic allodynia following ischemic injury [86]. If SCI pain could be eliminated, the quality of life could be greatly improved in patients; they would no longer suffer from pain and could take part in social aspects of life or earn money. 2008;63:981987987-988, 52. The utility for each model summarizes in Table 3. A. Webb and G. D. Muir, Sensorimotor behaviour following incomplete cervical spinal cord injury in the rat,, J. F. Ditunno, J. W. Little, A. Tessler, and A. S. Burns, Spinal shock revisited: a four-phase model,, F. Biering-Srensen, J. Scores are tabulated and considered to be an indicator of motor recovery. These endpoint measurements produce interpretable and comparable results between studies. The number of brisk foot withdrawals is recorded. Li XQ, Wang J, Fang B, Tan WF, Ma H. Intrathecal antagonism of microglial TLR4 reduces inflammatory damage to blood-spinal cord barrier following ischemia/reperfusion injury in rats Mol Brain. Pain behavior should not be measured in injured animals during maximal motor dysfunction. 2012;92:15911595, 53. Stereotactic radiosurgery improves locomotor recovery after spinal cord injury in rats Neurosurgery. These patients typically cannot only walk, but also lose bowel, bladder, and sexual functions. 2010;34:184192 192, 43. van Gorp S, Leerink M, Kakinohana O, Platoshyn O, Santucci C, Galik J, Joosten EA, Hruska-Plochan M, Goldberg D, Marsala S, Johe K, Ciacci JD, Marsala M. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation Stem Cell Res Ther. The tractive SCI model is a reliable animal model for studying pathological mechanisms and treatment of tractive SCI (Wang et al., 2011). The unique features of controlled displacement and monitoring of biomechanical parameters at the time of impact help to reduce outcome variability [105]. Spinal cord injury. Motor and sensory dysfunction has been periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds, and myogenic motor evoked potentials. Treatment effectiveness in animals with SCI is often measured simply by whether or not independent ambulation has occurred. A typical pathology is reduced blood flow to the peripheral nerve, resulting in demyelination or axonal degeneration, depending on the magnitude of ischemic injury. The animal skin is briskly stroked with a pencil point in a rostral to caudal direction. These features resemble allodynia and hyperalgesia experienced by humans suffering from central pain syndromes following spinal cord injury. Zheng YH, Fang Z, Cao P, Zheng T, Sun CH, Lu J, Shi RY. 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. 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). Touch-evoked agitation is another evaluation of mechanical allodynia [110] and can be used to test the animal response to tactile stimulation.