primary mechanisms hypothesized

The primary mechanisms hypothesized to be responsible for spasticity are increased motoneuron excitability [122, 123] and increased synaptic input, as a result of muscle stretch and reduced inhibitory mechanisms (presynaptic [124] and reciprocal inhibitions [125]). 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]. Therefore, motor deficit scores, such as BBB [95] and CBS [96], have been widely utilized [86, 90]. Testing continues for five or more stimuli after the first change in response, and the pattern of responses is converted to a 50% von Frey threshold using a previously described technique [109]. Photochemically induced spinal cord injury in the rat Brain Res. However, there have been few such relatively direct studies. classified SCI pain by location of the pain [23]. At-level and below-level neuropathic pains are then analyzed [57, 58]. Three to five minutes are allowed between each trial, and three trials are averaged for each limb. Observation and establishment of an animal model of tractive spinal cord injury in rats Chin J Traumatol. 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]. 2013;8:64, 23. II.Time limits for recovery after acute compression in dogs AMA Arch Neurol Psychiatry. Epidemiology demographics and pathophysiology of acute spinal cord injury Spine (Phila Pa 1976). Pain is subjective in humans, and interpretation of animal model results requires careful attention. Pain behavior should not be measured in injured animals during maximal motor dysfunction. You may be trying to access this site from a secured browser on the server. Zurita M, Aguayo C, Bonilla C, Otero L, Rico M, Rodriguez A, Vaquero J. Development of complete thoracic spinal cord transection model in rats for delayed transplantation of stem cells Spine (Phila Pa 1976). Seifert JL, Bell JE, Elmer BB, Sucato DJ, Romero MI. 2011, Article ID 939023, 11 pages, 2011. https://doi.org/10.1155/2011/939023, 1Department of Anesthesiology & Intensive Care, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan, 2Department of Breast Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, 3Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, 4Department of Pain Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. Like contusion injury in humans, rat contusion injury leads to the formation of both small and large cavities and fluid-filled cysts (Sroga et al., 2003; Norenberg et al., 2004). Norenberg MD, Smith J, Marcillo A. There are numerous experimental animal models of SCI, including the spinal cord ischemia-reperfusion injury model (Lafci et al., 2013), spinal cord traumatic injury model (Koozekanani et al., 1976), photochemical-induced SCI model (Piao et al., 2009), spinal cord transection model (Min et al., 2011), and bidirectional distraction SCI model (Seifert et al., 2011). 2012;29:16001613, 8. 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. Treatment effectiveness in animals with SCI is often measured simply by whether or not independent ambulation has occurred. 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). In chronic states, secondary overuse or abnormal use of structures, such as the arm and shoulder, occurs [17]. 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). Traumatic SCI is more prevalent in males than females (Sekhon and Fehlings, 2001). 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). These models have also been adapted for mice [2831]. 1976;44:429434, 18. Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury Neurotherapeutics. 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. 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, . Yu CG, Singh R, Crowdus C, Raza K, Kincer J, Geddes JW. Spinal cord injury leads to immediate impaired motor and sensory functions, which are also manifested over time. However, when SCI animal models are used for pain research, special attention should be paid to the concomitant conditions. Future studies should extend the scope of inquiry to include the psychosocial aspects of chronic pain and spinal cord injury. Liu L, Chi LT, Tu ZQ, Sheng B, Zhou ZK, Pei FX. The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury Prog Neurobiol. Gonzalez-Lara LE, Xu X, Hofstetrova K, Pniak A, Brown A, Foster PJ. Data is temporarily unavailable. Experimental failures with novel drugs are associated with adverse side effects and the lack of efficacy in humans. Cervical contusion is rarely reported, because life-threatening adverse effects could occur. 1995;12:121, 7. Thoracic or thoracoabdominal aortic aneurysm surgery may cause spinal cord ischemia. Some studies have predominately used rodents for in vivo SCI modeling and experimentation (Gonzalez-Lara et al., 2009; Basoglu et al., 2013). 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]. Basso DM, Beattie MS, Bresnahan JC. 1997;35:7685, 16. Nevertheless, this model could help to clarify pathophysiology of chronic, light pressure to the spinal cord. These include contusion impactors (Krishna et al., 2013) and clip compression (Alluin et al., 2011). 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. Only a small percentage of injuries, infections, or others causes that results in chronic pain syndrome actually develop chronic pain. Hartkopp A, Bronnum-Hansen H, Seidenschnur AM, Biering-Sorensen F. Survival and cause of death after traumatic spinal cord injury. A number of animal models of SCI exist and are primarily used to determine mechanisms of motor dysfunctions [24]. 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. However, it is likely that too many genes are involved [26]. (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 excitotoxic animal models, nearly 100% animals develop varying degrees of hypersensitivity to mechanical and thermal stimuli [98]. No related content is available yet for this article. In addition, genetic biomarkers could prove to be useful. According to the National Spinal Cord Injury Statistical Center, in 2005, 51% of SCI cases in the U.S. occurred in the cervical region (Akhtar et al., 2008). 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. Approximately 75% of individuals with SCI exhibit spasticity 1 year after injury and half undergo antispasticity treatment [121]. Vaquero C, Arce N, Agudo J, Martinez R, Garjal C, Diago MV. Methods for reproducible and controlled SCI models have been well described. 2004;21:13551370, 2. The Basso Mouse Scale (BMS), a 9-point rating scale, has been specially developed for mouse models [113]. Please try again soon. Apoptosis is critical for triggering collateral damage following primary injury to the spinal cord. 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. 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. Ackery A, Tator C, Krassioukov A. Motor vehicle collisions (MVCs) and falls are the leading causes of SCI, and a trend toward an increased prevalence of falls and MVC in developing countries is likely related to urbanization and increased use of motor vehicles. Search for Similar Articles Following mechanical injury to the spinal cord, a wave of secondary pathological changes occurs and amplifies the extent of initial damage. Kunkel-Bagden E, Dai HN, Bregman BS. modify the keyword list to augment your search. Lozos VA, Toumpoulis IK, Agrogiannis G, Giamarellos-Bourboulis EJ, Chamogeorgakis TP, Rizos IK, Patsouris ES, Anagnostopoulos CE, Rokkas CK. The pathology of human spinal cord injury: defining the problems J Neurotrauma. Nonetheless, the subjectivity of these measures has led to a decade-long search for surrogate biomarkers. Spinal cord injury is associated with permanent disability and decreased life expectancy (Hartkopp et al., 1997). 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. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. (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). Lee JS, Hong JM, Kim YJ. 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. They have used different weights falling from varied heights, leading to transversal compression on the spinal cord. The resultant photochemical reaction leads to vascular stasis, and voluntary motor function is consistently lost in the subacute phase of injury (Watson et al., 1986). A positive response is defined as a rapid withdrawal and/or licking of the paw immediately upon application of the stimulus. Characterization of a novel bidirectional distraction spinal cord injury animal model J Neurosci Methods. Because there is no curative treatment for SCI, establishing an ideal animal model is important to develop therapies for individuals suffering from SCI. A summary of results from 10 studies indicates that an average of 69% of the patients experienced pain, and nearly one-third of patients in pain rated their pain as severe [6]. 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. Although experimental methods of spinal cord injury pain lead to various behavioral outcomes, it is clear that some models respond similarly to pharmacological agents. The mechanisms underlying decreased inhibition below the lesion remain poorly understood [59]. 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. Stereotactic radiosurgery improves locomotor recovery after spinal cord injury in rats Neurosurgery. Pathology in visceral structures, such as urinary tract infection, bowel impaction, and renal calculi, generally results in nociceptive pain. 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. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Mechanical allodynia can be measured in various ways using the von Frey hair. Siddall and colleagues [16] classified SCI pain from spinal cord injury into two broad types, with three regions of pain. However, these procedures also induce mechanical hypoalgesia [107]. Animal spinal cord injury models and symptoms. These studies have brought to light the pathophysiology of SCI and a growing number of novel treatments that promote behavioral recovery. Piao MS, Lee JK, Jang JW, Kim SH, Kim HS. Briefly, animals are placed in Plexiglas boxes on an elevated glass plate heated by a radiant heat source directed by a beam of light to the planter surface of each paw through the glass plate (47C). Some error has occurred while processing your request. This method of inducing SCI may yield markedly different degrees of cord compression depending on the materials and apparatus. Lozos et al. In human SCI, trauma severity is not proportional to pain severity, because the method of injury varies. 2011;28:16111682, 42. van den Berg ME, Castellote JM, Mahillo-Fernandez I, de Pedro-Cuesta J. For information on cookies and how you can disable them visit our Privacy and Cookie Policy. The complete spinal transection injury model reflects symptoms of complete SCI patients. In the future, several points should be addressed. Copyright 2011 Aya Nakae et al. Antiallodynic effects of analgesics have been determined using this model [84, 85, 90]. The use of animal models has increased our knowledge of novel, effective, and safe clinical analgesics. A vascular clip is used for this procedure in mice [103]; the spinal cord becomes ischemic and mimics common clinical injuries and outcomes. Liu et al., A novel human foamy virus mediated gene transfer of GAD67 reduces neuropathic pain following spinal cord injury,, N. E. Saad, H. A. Amin, S. Chalouhi, S. A. Baki, S. J. Jabbur, and S. F. Atweh, Spinal pathways involved in supraspinal modulation of neuropathic manifestations in rats,, X. M. Peng, Z. G. Zhou, J. C. Glorioso, D. J. Fink, and M. Mata, Tumor necrosis factor-, J. Kim, Y. W. Yoon, S. K. Hong, and H. S. Na, Cold and mechanical allodynia in both hindpaws and tail following thoracic spinal cord hemisection in rats: time courses and their correlates,, B. C. Hains, K. M. Johnson, M. J. Eaton, W. D. Willis, and C. E. Hulsebosch, Serotonergic neural precursor cell grafts attenuate bilateral hyperexcitability of dorsal horn neurons after spinal hemisection in rat,, Y. S. Gwak, B. C. Hains, K. M. Johnson, and C. E. Hulsebosch, Effect of age at time of spinal cord injury on behavioral outcomes in rat,, C. D. Mills, B. C. Hains, K. M. Johnson, and C. E. Hulsebosch, Strain and model differences in behavioral outcomes after spinal cord injury in rat,, J. H.T. Despite the development of human imaging studies, such as functional MRI, the use of animal models of pain is a continuing necessity [5]. Either clip is dorsoventrally closed over the entire cord for 1min and then subsequently removed [58, 100102]. In both experimental and clinical SCI, contusion and compression are two of the most common injury types. Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury Exp Neurol. 2013;30:142159, 25. Because there is no curative treatment for spinal cord injury, establishing an ideal animal model is important to identify injury mechanisms and develop therapies for individuals suffering from spinal cord injuries. 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. (2008) investigated whether ischemic tolerance could be induced by ischemic preconditioning of the spinal cord in a swine model. By continuing to use this website you are giving consent to cookies being used. This lack of consistent correlation with functional outcome is another significant drawback with the use of surrogate markers. Therefore, cervical hemicontusion, following hemilaminectomy, is used to analyze the unilateral spinal cord contusion model. 2011;28:15891610, 21. Spasticity is a disabling complication that affects individuals with spinal cord injury [18, 120]. 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].

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