Hindawi Publishing Corporation
Journal of Biomedicine and Biotechnology
Volume 2011, Article ID 939023, 11 pages
doi:10.1155/2011/939023

Review Article
The Animal Model of Spinal Cord Injury as
an Experimental Pain Model
Aya Nakae,1 Kunihiro Nakai,2 Kenji Yano,2 Ko Hosokawa,3 Masahiko Shibata,4and Takashi Mashimo1
1 Department of Anesthesiology & Intensive Care, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita,

Osaka 565-0871, Japan
2 Department of Breast Regenerative Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
3 Department of Plastic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
4 Department of Pain Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

Correspondence should be addressed to Aya Nakae, anakae@anes.med.osaka-u.ac.jp
Received 13 September 2010; Accepted 19 December 2010
Academic Editor: Andrea Vecchione
Copyright © 2011 Aya Nakae et al. 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.
Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems,
as well as motor dysfunctions, spinal cord injury research has proven to be complex and diﬃcult. Furthermore, many types of pain
are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord
injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results canbe easily misunderstood and falsely interpreted. 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. The present paper summarizes results fromanimal models of spinal cord injury, as well as the most eﬀective use of these models.

1. Introduction
Spinal cord injury (SCI) often results in severe motor dysfunction, such as complete paralysis. These patients typicallycannot only walk, but also lose bowel, bladder, and sexualfunctions. Pain impact following SCI has been reported as
37% of higher-level SCI patients with pain and 23% of lowerlevel SCI patients with pain; given the choice, these patientswould trade pain relief for loss of bladder, bowel, or sexualfunctions [1]. Pain management is, therefore, an important
health problem and topic of study.
Pain experiments with human subjects have proven to
be practically challenging, fundamentally subjective, andethically self-limiting. For these reasons, there remains a needfor the use of laboratory animal models of pain. Pain issubjective in humans, and interpretation of animal model
results requires careful attention. In fact, some have called
for the abandonment of animal pain studies in favor of more
extensive human testing.
A number of animal models of SCI exist and are primarily used to determine mechanisms of motor dysfunctions[2–4]. Recently, these various SCI animal models have beenutilized for pain studies [5]. However, when SCI animalmodels are used for pain research, special attention shouldbe paid to the concomitant conditions. 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.

2. Pain in SCI Patients2.1. SCI and the Social Impact. SCI occurs in most countries
at an annual rate of 20–40 individuals per million. SCI is adevastating event that results in motor dysfunction below
the level of lesion, as well as development of chronic pain
syndromes. Studies have reported the prevalence of pain in
SCI patients. A summary of results from 10 studies indicatesthat an average of 69% of the patients experienced pain, andnearly one-third of patients in pain rated their pain as severe[6]. The stakes are enormous, given the impact of pain on theeconomy (pain-related treatment costs 1 trillion US dollars

2
per year in developed countries) [7]. If SCI pain could be
eliminated, the quality of life could be greatly improved inpatients; they would no longer suﬀer from pain and could
take part in social aspects of life or earn money.
2.2. Spinal Cord Injury and Chronic Pain. Following mechanical injury to the spinal cord, a wave of secondary pathological changes occurs and amplifies the extent of initialdamage. Apoptosis is critical for triggering collateral damage
following primary injury to the spinal cord. Spontaneous andevoked pain is frequent in traumatic or ischemic spinal cord
injury.
In complete and partial spinal lesions, chronic pain
develops within months following injury [8]. Up to 80%
of patients experience clinically significant pain, which is
described as burning, stabbing, and/or electric-like [9, 10].
Post-SCI pain results in drastically impaired daily routinesand quality of life to a greater extent than motor impairment[11]; it is refractory to clinical treatments, despite a variety ofneurosurgical, pharmacological, and behavioral therapeuticstrategies [12, 13]. The pain so greatly aﬀects quality of lifethat depression and suicide frequently result [14, 15].

3. Chronic Pain Classification in SCI(Tables 1 and 2)
Siddall and colleagues [16] classified SCI pain from spinal
cord injury into two broad types, with three regions of pain.
3.1. Nociceptive Pain. It is crucial for a pain clinician to distinguish between nociceptive or neuropathic pain, because
the clinical approach for each is diﬀerent. The first choicefor nociceptive pain treatment following SCI is often anonsteroidal, anti-inflammatory drug, or opiate, which often
results in suﬃcient pain control.
3.1.1. Musculoskeletal Pain. Musculoskeletal pain is very
common in SCI patients. In chronic states, secondary
overuse or abnormal use of structures, such as the arm andshoulder, occurs [17]. 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 beneeded in many cases [18].
3.1.2. Visceral Pain. Pathology in visceral structures, such as
urinary tract infection, bowel impaction, and renal calculi,
generally results in nociceptive pain. Visceral pain usuallyexhibits a delayed onset following SCI, which could be due
to normal aﬀerent input via sympathetic or vagal nerves inparaplegics or via the vagus nerve in tetraplegics [19, 20].
Patients with upper thoracic injury or cervical SCI may
present with autonomic dysreflexia headache, because ofbowel impaction or bladder distension.
3.2. Neuropathic Pain. SCI often results in neuropathic pain,
which is diﬃcult to treat and exhibits various patterns due toits pathology.

Journal of Biomedicine and Biotechnology
Table 1: Classification of the Spinal Cord Injury Pain Task Force of
the International Association of the Study of Pain.
Broad type

Broad system

Nociceptive

Musculoskeletal

Visceral

Neuropathic

Above-level

At-level

Below-levelAﬀected structures/Pathologies
Bone, joint, muscle trauma, or
inflammation
Mechanical instability
Muscle spasm
Secondary overuse
Renal calculus (kidney stones)
Bowel and sphincter
dysfunctions
Headache by autonomic
dysreflexia
Compression mononeuropathy
Complex Regional Pain
Syndrome
Nerve root compression (cauda
equine)Syringomyelia
Spinal cord trauma/ischemia
Dual-level cord and root
trauma (double-lesion
syndrome)
Spinal cord trauma/ischemia

Table 2: SCI pain classification by Bryce and Ragnarsson.
LocationAbove-level nociceptive

Type Etiologic subtypes
1 Mechanical and musculoskeletal
2 Autonomic dysreflexia headache
3 Others
neuropathic
4 Compressive neuropathy
5 Others
At-level
nociceptive
6 Mechanical and musculoskeletal
7 Visceralneuropathic
8 Central
9 Radiculopathy
10 Compressive neuropathy
Complex Regional Pain
11
Syndrome
Below-level nociceptive
12 Mechanical and musculoskeletal
13 Visceralneuropathic 14 Central
15 Other

3.2.1. At-Level Pain. At-level pain occurs in dermatomes
near the spinal injury and develops shortly after the injury.
The pain is often characterized as stabbing or stimulusindependent and is accompanied by allodynia [21, 22].
3.2.2. Below-Level Pain. Below-level pain is localized todermatomes distal to the injury site and develops more
gradually than at level pain; it is often classified as a stimulusindependent, continuous, burning pain [21, 22].

Journal of Biomedicine and Biotechnology
3.2.3. Above-level Pain. Above-level pain occurs at dermatomes cranial to the injury site [21, 22].
3.3. Other Classification of SCI Pain (Table 2). Bryce et al.
classified SCI pain by location of the pain [23]. In terms ofanimal behavior, this classification helps to provide a better
understanding of pain pathology. In basic pain research,pain is defined as neuropathic or nociceptive. Similarly, SCI
pain is complex and the pathology should be taken into
consideration at the same time. It is important to understandthe pathologies in each model.

4. The Role of Animal Model
Human self-ratings of pain, using questionnaires and scales,
are reliable, accurate, and versatile for measuring experimental and clinical pain [24]. Nonetheless, the subjectivity ofthese measures has led to a decade-long search for surrogate
biomarkers. To date, an objective surrogate with acceptablehigh sensitivity and specificity has not been identified.
However, individual function-imaging scans could provide
a reliable and objective measurement of subjective pain
perception [25]. In addition, genetic biomarkers could prove
to be useful. However, it is likely that too many genes
are involved [26]. Moreover, genomic DNA variants could
predict trait sensitivity to pain rather than ongoing levels of
pain. Only a small percentage of injuries, infections, or others
causes that results in chronic pain syndrome actually develop
chronic pain. Therefore, in human studies, it will be diﬃcult
to determine the correlation between genetic backgroundand pain severity. Furthermore, common clinical pain conditions, such as back pain, are too polygenic to be eﬀectively
modeled and genetically understood.
Animal models cannot self-report. In response to noxious stimuli, behaviors can be reliably and objectively scored,
although these simple reflexes or innate responses (suchas licking an inflamed paw) seem to lack clinical validity.
Indeed, experiments with behavioral measurements of pain
in animal models have become more common. According tostudies published in flagship journals, pain studies compriseapproximately 25% of total studies, more than any other fieldof study [27].
The animal model of pain plays a central role in analgesic
drug development and the fundamental mechanisms thatdrive it. Despite the development of human imaging studies,such as functional MRI, the use of animal models of pain is acontinuing necessity [5].

5. Spinal Cord Injury Dynamics and Procedures
Several models of neuropathic pain due to spinal cord injury
have been simulated in rats. 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. These models have also
been adapted for mice [28–31]. The development of reliable
neurotrauma mouse models provides great promise for3
evaluating overexpression or inactivation of certain genes on
lesion pathophysiology and functional outcome. 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]. The utility foreach model summarizes in Table 3.
5.1. Contusive or Hemicontusive Models. Spinal contusion is
the oldest and most widely used animal model. In addition
to motor dysfunction, this injury elicits sensory dysfunction,
including neuropathic pain, tactile allodynia, and thermal
hyperalgesia [34, 35]. Cervical contusion is rarely reported,because life-threatening adverse eﬀects could occur. Therefore, cervical hemicontusion, following hemilaminectomy, isused to analyze the unilateral spinal cord contusion model.
Because motor dysfunction appears in the forelimbs, painrelated behavior is diﬃcult to estimate, and for this reason,
cervical contusion is often utilized for motor functional
analysis [2, 3]. The thoracic spinal cord contusion modelis the most popular pain research model and is inducedwith impactors, such as the weight-drop impactor [36]. In
brief, the exposed spinal cord is injured by dropping a 10.0g rod from specified heights [37, 38]. After 2 or 3 weeks,motor dysfunction is recovered and pain behavior can beanalyzed. The impact of the injury tends to vary. Therefore,
especially in short distances from the rod to spinal cord, pain
behavior does not always appear. It is diﬃcult to bilaterally
drop the rod onto the spinal cord. Following injury, motor
function analysis is needed to exclude unilateral paralysis andthe possibility of unilateral contusion. Abnormal sensations
due to mechanical, thermal, or cold stimuli are observed forseveral weeks or longer [32, 33, 39–52], and all regions (at-,above-, below-level) of allodynia are analyzed [53–56].
5.2. Transection or Hemisection Models. The complete spinal
transection injury model reflects symptoms of complete SCI
patients. Following laminectomy, spinal cord transection
is performed with spring scissors. Occasionally, to attach
the two ends for regeneration, a sterile, gel foam is placed
between the two resected spinal cord ends. At-level andbelow-level neuropathic pains are then analyzed [57, 58].
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 useof this model.
The partial spinal transection injury model (hemisection) has become popular in neuropathic pain studies [61–78]. Motor dysfunction appears only in the ipsilateral injured
side and persists from 5 days to 4 weeks [64, 75]. Mechanicalallodynia and thermal hyperalgesia are bilaterally observed inabove-level and below-level cases [61, 76–81].
5.3. Photochemical Model. Over the past two decades, thephotochemical model of spinal cord injury, developed by
Watson et al. [82], has proven to be one of the mostreliable and reproducible graded experimental rat modelsof spinal cord injury [83–94] and has been widely used to
study neurotrauma in mice [88]. The biggest advantage of4

Journal of Biomedicine and Biotechnology
Table 3: Animal spinal cord injury models and symptoms.
Impact tospinal cord

Injury area

Laterality anddevices
CervicalTransection

Compression

ThoracicSensory abnormality
Lumbar At-level Below-level

Duration
Allodynia

Maximal motor
dysfunction

Several weeks or
moreLess than 4 weeks

Unilateral

1–5 weeks or more

Ipsilateral to
injury: 4 weeks

Contusion

Weeks to months

1-2 weeks

Bilateral

Above-level×

Hemi-contusion
Clip

3 weeks
4 weeks

4 weeks severe
injury

Displacement

4–6 weeks

2 weeks

Canal stenosis

8 days or
hypoalgesia: severe
injuryimpossible

or ×

Photochemically
Excitotoxic
Spinothalamic
tract lesions

10–20 days?

Various

5 weeks or more
Several weeks

Less than 1week

Many spinal cord injury models exist for pain research. Pain behavior should not be measured in injured animals during maximal motor dysfunction.

this method is that the resulting injury does not induce
mechanical trauma to the cord, because there is no needfor laminectomy. Instead, an intravascular photochemical
reaction occurs through the use of a dye that is activated byan argon ion laser to produce single oxygen molecules at theendothelial surface of spinal cord vessels. This results in an
intense platelet response, as well as subsequent vessel occlusion and parenchymal tissue infarction [83]; the pathology
is of a purely ischemic origin. Motor deficits are related toirradiation duration, as well as mechanical allodynia (cold,
not thermal), which lasts for several days [91]. Following
application of the von Frey filament to the trunk, behavioral
analysis is performed according to vocalization threshold.
Antiallodynic eﬀects of analgesics have been determinedusing this model [84, 85, 90]. However, extent of injury is
diﬃcult to control. Therefore, motor deficit scores, such as
BBB [95] and CBS [96], have been widely utilized [86, 90].

following ischemic injury [86]. In excitotoxic animal models,nearly 100% animals develop varying degrees of hypersensitivity to mechanical and thermal stimuli [98].

5.4. Excitotoxic Models. Intraspinal or intrathecally injectionof some excitotoxins, such as quisqualic acid or other excitatory amino acids (glutamate, N-methylasparate, and kainicacid), produces long-lasting spontaneous pain, mechanicalallodynia, and thermal hyperalgesia in rats and mice [97,98]. Following excitotoxin injections, neuronal loss, cavity
formation, astrocytic scaring, and prominent inflammation
occur. The advantage of this model is the ability to correlatespecific areas of tissue damage with behavioral changes.
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

5.5.2. Spinal Cord Displacement. The spinal cord displacement model attempts to regulate trauma impact by controlling displacement length of the spinal cord. Through theuse of this model, a cutoﬀ for normal sensory function has
been determined [104]. In human SCI, trauma severity is
not proportional to pain severity, because the method of
injury varies. The unique features of controlled displacement
and monitoring of biomechanical parameters at the time of
impact help to reduce outcome variability [105].

5.5. Other Mechanical Spinal Cord Injuries
5.5.1. Clip Compression Injury. Clip compression injury
resembles spinal contusion injury at the point of the injury
caused by pressure to the spinal cord. Following laminectomy, compression injury is induced with clips calibrated
to exert a force of 50 or 35 g. The 50-g clip induces severe
injury and the 35-g clip induces moderate injury. Either clip
is dorsoventrally closed over the entire cord for 1 min andthen subsequently removed [58, 100–102]. A vascular clip
is used for this procedure in mice [103]; the spinal cord
becomes ischemic and mimics common clinical injuries andoutcomes.

5.5.3. Canal Stenosis. Lumbar canal stenosis is due toentrapment of the cauda equine and/or lumber nerveroots by hypertrophy of osseous and soft tissue structures

Journal of Biomedicine and Biotechnology
surrounding the lumbar spinal canal. A typical pathology
is reduced blood flow to the peripheral nerve, resulting indemyelination or axonal degeneration, depending on themagnitude of ischemic injury. Canal stenosis can also be
termed a spinal cord injury model, in which square-shaped
pieces of silicon are placed into the epidural space in the rat[106, 107]. However, these procedures also induce mechanical hypoalgesia [107]. Nevertheless, this model could help
to clarify pathophysiology of chronic, light pressure to thespinal cord.
5.5.4. Spinothalamic Tract Lesions. The spinothalamic tract
is the core pain pathway in the spinal cord. This model isdesigned to lesion only the spinothalamic tract area using
a tungsten microelectrode. Although this model injures
the unilateral spinothalamic tract, bilateral above- andbelow-level hyperalgesia, as well as allodynia, is induced
and can persist for many weeks. These features resemble
allodynia and hyperalgesia experienced by humans suﬀeringfrom central pain syndromes following spinal cord injury.
Therefore, this model could provide useful and novel insights
into the underlying biological mechanisms of spinal cord
injury [108].

6. Pain-Related Behavior As
an Evaluation of Symptoms
Pain-related behavior is recorded using various devices
applied to the forelimbs, hindlimbs, trunk, and face. If
pain behavior appears in the face, it is considered to reflect
the reaction to supraspinal mechanisms, because sensory
function in the face is regulated by the trigeminal nerve(a cranial nerve). In thoracic spinal cord injury, trunk
allodynia reflects at-level neuropathic pain, and allodynia in
the hindlimb reflects below-level neuropathic pain. Forelimb
allodynia reflects at-level neuropathic pain in cervical injury
and above-level neuropathic pain in other injuries.
Abnormal pain behavior is a result of three diﬀerent
stimulations: mechanical, thermal, and cold.
6.1. Mechanical Allodynia. Mechanical allodynia can bemeasured in various ways using the von Frey hair. In one of
the methods, the “up-down method” [109], each von Freyhair is applied to the test area for 2-3 s, with a 1-2-minuteinterval between stimuli. The trial begins with applicationof the 15-mN von Frey probe to the hindpaws. A positive
response is defined as a rapid withdrawal and/or licking of
the paw immediately upon application of the stimulus. The
von Frey hair can also be used to determine vocalizationthreshold to graded mechanical allodynia as a means toevaluate at-level neuropathic pain in the trunk [92]. Whena positive response to stimulus occurs, the next smaller vonFrey hair is applied. If a negative response occurs, the next
higher force is applied. Testing continues for five or morestimuli after the first change in response, and the pattern of
responses is converted to a 50% von Frey threshold using apreviously described technique [109]. If the animal showsno response to the highest von Frey hair (160 mN), a von

5Frey threshold of 260 mN, corresponding to the next log
increment in potential von Frey probes, is assigned to thethreshold.
Touch-evoked agitation is another evaluation of mechanical allodynia [110] and can be used to test the animal
response to tactile stimulation. The animal skin is briskly
stroked with a pencil point in a rostral to caudal direction.
The animal response is graded with a score of 0: no response,
1: moderate eﬀorts to avoid the probe, transient vocalization,and 2: vigorous eﬀorts to escape the stimulus, frequent andsustained vocalization in response to the probe.
Pathological reactions between the von Frey probe andpencil point vary due to reactions to the von Frey hair(caused by A-delta-fiber and C-fiber) or the pencil (A-beta
fiber).
6.2. Thermal Hyperalgesia. Thermal hyperalgesia can bemeasured by latency of paw withdrawal in response to aradiant heat source [111]. Briefly, animals are placed in
Plexiglas boxes on an elevated glass plate heated by a radiantheat source directed by a beam of light to the planter surfaceof each paw through the glass plate (47◦ C). The light beam
is automatically turned oﬀ by a photocell upon limb-lift,
allowing for measurement of time between stimulus startand paw withdrawal (paw withdrawal latency). Three to fiveminutes are allowed between each trial, and three trials areaveraged for each limb.
6.3. Cold Allodynia. Cold sensitivity to acetone can bequantified by foot withdrawal frequency [112]. A total of
100 μL acetone is applied to the paw planter surface using aplastic tubule connected to a 1 ml syringe. Acetone is applied
5 times to each paw at an interval of at least 5 minutes. The
number of brisk foot withdrawals is recorded.

7. Evaluation of Motor Functions in
the Spinal Cord Injury Model
Locomotor function is observed and recorded using the
Basso, Beattie, and Bresnahan (BBB) Locomotor Rating Scale[95]. Briefly, the BBB is a 22-point ordinal scale ranging from0 (no discernable hindlimb movement) to 21 (consistentand coordinated gait with parallel paw placement of thehindlimb and consistent trunk stability). Scores from 0
to 7 rank early phase of recovery, with return of isolated
movements from three joints (hip, knee, and ankle); scoresfrom 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 ofrecovery, with return of toe clearance during the step phase,
predominant paw position, trunk stability, and tail position.
Scores are tabulated and considered to be an indicator of
motor recovery.
The Basso Mouse Scale (BMS), a 9-point rating scale,has been specially developed for mouse models [113]. An
additional scoring systems, described by Gale et al. [96] andtermed the Combined Behavioral Score (CBS) (Table 4), hasbeen used to measure locomotor function.

6
Following cervical spinal cord injury, recovery of forelimb function can be measured [114] by indicators suchas the grooming test and forelimb asymmetry test [115].
Forelimb grooming function has been assessed using ascoring system originally developed to examine recovery
in a rat brachial plexus reconstruction model [116]. The
forelimb asymmetry, or paw preference test, is sensitive toasymmetries produced by a variety of CNS insults [117].
In addition, forelimb motor function recovery and pain
behavior should be coanalyzed, because behavior is a resultof motor functions [118].

Journal of Biomedicine and Biotechnology
Table 4: Combined Behavioral Score (CBS), as reported by Gale etal. [96].
Generaldescription
Motor score
0
1
2
3
4

8. Future Direction and Conclusions
5

8.1. Spinal Cord Injury As a Musculoskeletal Pain Model.
Spinal cord injury leads to immediate impaired motor andsensory functions, which are also manifested over time.
Following an initial period of spinal shock, reflexes become
reduced and a disturbing hyperreflexia develops, which isoften referred to as spasticity [119].
Spasticity is a disabling complication that aﬀects individuals with spinal cord injury [18, 120]. Approximately 75%
of individuals with SCI exhibit spasticity 1 year after injury
and half undergo antispasticity treatment [121]. Significant
scientific interest has been devoted to spasticity over the past
10–15 years as an example of plastic changes occurring distal
to a central lesion.
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]). The mechanisms
underlying decreased inhibition below the lesion remain
poorly understood [59].
The most commonly proposed mechanisms to accountfor decreased inhibition following spinal cord injury
include disruptions of facilitatory supraspinal input toinhibitory interneurons [59, 126]. 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].
The spinal cord injury model, in particular the spinal
transaction model, is considered useful for spasticity
research. Because spasticity results in musculoskeletal pain,
the spinal cord injury model could be considered a musculoskeletal pain model.
8.2. Spinal Cord Injury As a Visceral Pain Model. Visceralpain in spinal cord injury commonly triggers autonomic dysreflexia, a potentially life-threatening hypertensive syndrome
due to high thoracic spinal cord injury. Pathology correlateswith increased sprouting of primary aﬀerent c-fibers into
the spinal cord. During motor dysfunction, visceral painrelated behavior is diﬃcult to analyze. However, based on
the above-described mechanisms, a morphological approachto spinal complete transection injury has been utilized[128].

Toe spread0
1
2
Righting
01
2
3
Extension
withdrawal
0
1
2
Placing0
12Inclined plate01
2
3

Points0515Normal walking
Walks with mild deficit
Hindlimb can support weight
Frequent movement of hindlimb, noweight support
Minor movement in hindlimb, noweight bearing
No movement in hindlimb, no weightbearing25

Normal, full, toe spread
Partial spreading of toes
No spreading of toes

0
2.5
5

Normal righting, counter to directionof roll
Weakened attempt to right
Delayed attempt to right
Delayed attempt to right itself

40
45

0
5
10
15

0

NormalWeak and slow reflex to withdraw
hindlimb
No withdrawal reflex

2.5

Normal placing
Weak attempt to place footNo attempt to place foot

0
2.5
5

65∼70/deg
55∼60
40∼50
<40

0
5
10
15

5

8.3. Limitations of Animal Models of Chronic Pain. Limited
success in the pain field during the past few decades has
resulted in a plethora of basic scientific data. The useof animal models has increased our knowledge of novel,eﬀective, and safe clinical analgesics. Experimental failureswith novel drugs are associated with adverse side eﬀects andthe lack of eﬃcacy in humans. In addition, psychosocial
aspects of chronic pain due to spinal cord injury havebeen completely omitted, despite a large body of knowledgeemphasizing the importance of these factors in chronic pain.
Future studies should extend the scope of inquiry to include
the psychosocial aspects of chronic pain and spinal cord
injury.

Journal of Biomedicine and Biotechnology
8.4. Conclusion. By widening the number of animal modelsof spinal cord injury, new challenges have emerged. Althoughexperimental methods of spinal cord injury pain lead tovarious behavioral outcomes, it is clear that some models
respond similarly to pharmacological agents. This suggeststhat common mechanisms could underlie specific symptoms
derived from various injury conditions. Etiologies of spinal
cord injury pain could vary. However, by focusing on various
symptoms of spinal cord injury pain, treatment possibilities
for pathologies of spinal cord injury pain could emerge.
Continuous basic and clinical studies focused on diﬀerent aspects of spinal cord injury pain are needed to better
understand the mechanisms involved.

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