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Published in final edited form as:
Adv Exp Med Biol. 2012 ; 760: 74–88.

CHRONIC PAIN FOLLOWING SPINAL CORD INJURY
Radi Masri*,1,2 and Asaf Keller2
1Department of Endodontics, Prosthodontics and Operative Dentistry, Baltimore College of Dental
Surgery, University of Maryland Baltimore, Baltimore, Maryland, USA
2Department of Anatomy and Neurobiology, Medical School, University of Maryland Baltimore,

Baltimore, Maryland, USA

Abstract

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Most patients with insults to the spinal cord or central nervous system suffer from excruciating,unrelenting, chronic pain that is largely resistant to treatment. This condition affects a large
percentage of spinal cord injury patients, and numerous patients with multiple sclerosis, stroke andother conditions. Despite the recent advances in basic science and clinical research thepathophysiological mechanisms of pain following spinal cord injury remain unknown. Here we
describe a novel mechanism of loss of inhibition within the thalamus that may predispose for thedevelopment of this chronic pain and discuss a potential treatment that may restore inhibition andameliorate pain.

INTRODUCTION
According to the National Spinal Cord Injury Statistical Center, the number of people in the
United States who suffer from spinal cord injury is approximately 259,000,1 with somestudies reporting an even higher incidence (1,275,000 individuals).2 It is estimated that the
number of individuals suffering from SCI increases by approximately 12,000 new cases
every year with many of these injuries occuring between the ages of 16 and 30.1 Injury to
the spinal cord is devastating and leads to catastrophic consequences such as decreased
ability to walk or move,3 loss of sexual function,4 diminished ability to control bladder orbowel function5 and the development of debilitating pain.6

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Pain resulting from spinal cord injury is referred to as central pain which is “pain initiated orcaused by a primary lesion or dysfunction in the central nervous system”.7 The pain is mostoften steady and unrelenting, and has been described “as if knives heated in Hell‘s hottest
corner were tearing me to pieces.”8 Central pain can be initiated by a variety of conditions
and insults at any level of the spinal cord and the brain. The most common conditions arespinal cord injuries, multiple sclerosis (MS) and cerebrovascular lesions (stroke). The
prevalence of pain in these conditions is alarmingly high: as many as 60–80% of spinal cord
injury patients experience pain9–15 with at least 1/3 of the patients reporting severe pain.16
In MS patients almost 30% develop chronic neuropathic pain and in stroke patients theprevalence is as high as 10%.6,17,18 Because spinal cord injury is the most common etiology
for central pain, this chapter is focused on pain resulting from spinal cord injury.

©2012 Landes Bioscience and Springer Science+Business Media.
*

Corresponding Author: Radi Masri—radi.masri@gmail.com.

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PAIN CHARACTERISTICS FOLLOWING SPINAL CORD INJURY
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Several distinct types of pain can develop following spinal cord injury. One that can beobserved in patients with spinal cord injury is musculoskeletal pain occurring due to muscle
spasm, or due to overuse or abnormal use of structures such as the arms or the shoulders.19
The pain is often dull, aching and is relieved by physical therapy, exercise, non steroidal
anti-inflammatory treatments (NSAIDs) and opiods. Another type of pain is visceral pain in
the abdomen, which is dull, cramping and located in a region with intact innervation and isthought to occur due to normal peripheral inputs from sympathetic or vagus nerve.20,21 Bothof these types of pain, musculoskeletal and visceral, have delayed onset after injury and areclassified as nociceptive pains because they arise from stimulation or activity of peripheral
nociceptive afferents.22

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However, the most debilitating pain and puzzling is the presence of sharp, shooting, andburning neuropathic pain. This pain is spontaneous in the majority of patients but canmanifest both as an increased pain with noxious stimulation (hyperalgesia) and as pain in
response to previously innocuous stimuli (allodynia).18,23–25 Neuropathic pain in patientswith spinal cord injury can be classified into three categories based on the location of thepainful region relative to the location of the spinal injury: (1) Below-level pain: The pain isdiffuse and located in areas with interrupted sensory innervation below the level of spinal
injury; (2) At-level pain at the border of normal and interrupted sensory innervation anddistributed within a band of 2 to 4 segments surrounding the level of injury and (3) Abovelevel pain in regions with preserved sensory inputs above the level of injury. Neuropathic
pain following spinal cord injury is largely resistant to conventional pharmacologic
treatments26 and to this date the pathophysiological mechanisms involved in thedevelopment of central neuropathic pain remain a mystery and effective treatments arelacking. Therefore, the study of the mechanisms of central pain and the development ofeffective treatments and animal models that recapitulate the clinical characteristics of thiscondition are needed.

ANIMAL MODELS OF SPINAL CORD INJURY PAIN

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Several animal models have been developed to study spinal cord injury pain (Table 1). In allof these models, the location, the extent and the means to produce injury vary. Some use
controlled spinal contusions to mimic clinical traumatic injuries.27–29 Others have usedischemic lesions,30,31 or a neurotoxic chemical injection into the spinal cord,32,33 whereassome have used cuts to sever the spinal cord (hemisection),34,35 or localized regions in the
spinal cord (cordotomy).36,37 Most of these models rely on measures of evoked pain andhypersensitivity, such as mechanical and thermal withdrawal thresholds. However, they
commonly do not attempt to quantify spontaneous pain, which is the single most commonand debilitating complaint from spinal cord injury patients.15,16,38
We have demonstrated that localized electrolytic lesions in the anterolateral quadrant of the
spinal cord result in consistent, long lasting below- and above-level mechanical and thermal
hyperalgesia (Fig. 1).39,40 Immediately following the spinal lesion, hindpaw withdrawal
thresholds to mechanical stimulation of the dorsal paw surface transiently increased(hypoalgesia). Subsequently, significant reductions in thresholds (hyperalgesia) were
evident bilaterally by 14 days post-lesion. The reduction in withdrawal threshold persisted
for at least 42 weeks. Sham surgery had no effect on mechanical withdrawal thresholds oneither the ipsilateral or the contralateral hindpaw.39 We also tested these animals using amodification of a conditioned place preference paradigm described by King et al,41 to assay
if animals with spinal lesions exhibit signs of spontaneous pain. We placed the animals in acustom built, automated 2-chamber box. The walls of one chamber were white with

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horizontal black stripes and the walls of the other chamber were white with vertical black
stripes. Rats with spinal cord lesions and sham-operated controls were habituated to theconditioned place preference box for 3 days and were permitted to move freely between thetwo chambers for 30 minutes. After habituation, and before conditioning, the time spent ineach chamber was recorded to determine each rat’s preference. Rats then underwent a 3-day
conditioning phase in which they received either an intraventricular microinjection ofvehicle (control: 5 µl saline followed by 10 µl saline flush); or an intraventricular
microinjection of clonidine, an alpha 2-adrenergic agonist (analgesic: 5 µl [2 mg/mL]
followed by 10 µl saline flush). Animals with spinal cord lesions, but not control animals,
develop a significant preference to the analgesic-paired chamber compared to the salinepaired chamber (unpublished data). These findings are consistent with King et al,41 andsuggest that animals with spinal cord lesion exhibit signs of tonic pain.

MECHANISMS OF SPINAL CORD INJURY PAIN
Since the first published description of central pain, over 120 years ago,42,43 numerous
hypotheses have been proposed to explain its pathophysiology.6,18,44,45 Many weredisproved with time, and many remain controversial. Fortunately, despite the clinicalvariability in presentation and variability in size, location and causes of spinal cord injury,
there is general agreement on a number of pathophysiological factors:

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Many of the earliest reported cases of central pain are based on pain caused by damage or
injury to the thalamus.43,46,47 As a result, thalamic abnormalities were thought to berequired for development of pain and the condition was referred to for decades by themisleading term “thalamic pain”. Research since that time has established that central pain
can result from damage to any structure along the afferent spinothalamocortical pathwaythat conveys pain and temperature information.18,48–52 This pathway includes: The
spinothalamic tract (STT) in the spinal cord and brainstem; thalamic nuclei that receive STT
input, including the posterior thalamus (PO), the mediodorsal thalamus (MD) and theventroposterior complex (VP); the internal capsule; and cortical areas such as the primary(S1) and second (S2) somatosensory cortices.53,54 Damage to the spinothalamocorticalpathway is, in fact, necessary for central pain development. There are no documented casesof pain resulting from central nervous system lesions that spare it, such as lesions involving
only the dorsal column-medial lemniscal pathway.44 Consistent with an obligatory role for
the STT is the finding that essentially all central pain patients have altered pain andtemperature sensation, while abnormalities of tactile sensation occur in only a subset ofpatients.18,49,55 Unfortunately, the consensus appears to end there as there are several
hypotheses regarding the mechanisms of central pain.

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Most of our knowledge regarding molecular, cellular and physiological changes following
spinal cord injury comes from studies performed in animal models of spinal cord injury
pain. Hyperalgesia and pain following spinal cord injury can result from maladaptive plasticchanges throughout the neural axis. In the spinal cord there are massive changes following
injury that include: Ischemia, necrosis, deafferentation, re-organization and sprouting inprimary afferents, the activation of astrocytes and glia and the release of inflammatory
mediators and neurotoxic excitatory amino acids in the extracellular space.35,56–58
These changes have far reaching consequences that compromise the normal function of not
only the surrounding local neurons but also their distant targets within the central nervous
system. Indeed, the delayed onset of pain and the diffuse localization of painful symptoms
suggest that the pathophysiology does not reflect only direct effects at the denervated spinal
segments. Rather, these features strongly suggest the occurrence of maladaptive plasticity insupraspinal structures at which inputs from various body parts converge. Consistent with

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this notion, it has been shown repeatedly that spinal cord injury is associated with increased
activity, increased spike bursts and changes in glial activation in the thalamus.40,59–61
However, the mechanism by which these central maladaptive changes occur requires morestudy.
One hypothesis that remains in favor, almost a century since it was first formulated, is that
central pain results from abnormally suppressed inhibition in the thalamus47 however, thesite of operation of this dis-inhibition remains unknown.18,44 For example, it has beenargued that the medial lemniscal pathway normally inhibits the spinothalamic system, andthat this inhibition is suppressed in central pain. It has been proposed that either descending
cortical inputs or ascending spinal inputs to the thalamus are involved in this disinhibition.47,62 A more recent elaboration of the Head and Holmes hypothesis47 posits thatthe disinhibition results from a loss of the discriminative thermosensory representation in thecentral nervous system.63 This “thermosensory disinhibition hypothesis” assumes that pain
is relayed from the spinal cord through independent thalamic pain/temperature nuclei thatserve as specific relays in the ascending pain system. However, this viewpoint is
controversial and remains unresolved.

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Loss of inhibition has also been implicated in the pathogenesis of central pain and is thought
to alter the firing properties of thalamic neurons, rendering them more likely to produce
spontaneous and evoked bursts of action potentials.64,65 However, some have argued thatthe incidence and properties of these bursts in central pain do not differ significantly than incontrols.66 In sum, remaining unknown are the mechanisms for the engagement ofinhibition, the source of this inhibition, and the specific nuclei affected.

ABNORMAL INHIBITION IN THE THALAMUS
A unique source of inhibition to the thalamus is the aptly named zona incerta (ZI) or “zoneof uncertainty”. The ZI receives nociceptive inputs through the STT,67,68 and has been
implicated in a variety of pain related functions.69,70 A striking feature of ZI is its target
specificity: In all sensory systems it provides inhibitory inputs exclusively to “higher-order”
thalamic nuclei (e.g., posterior nucleus in the somatosensory system and the inferior
pulvinar in the visual system) and avoids first-order thalamic nuclei (e.g., ventroposterior in
the somatosensory system and the lateral geniculate in the visual system).71,72

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ZI sends a dense GABAergic projection upon the posterior nucleus of the thalamus(PO),71,73 a nucleus critically involved in nociceptive processing.74–77 ZI exerts potent feedforward and tonic inhibition to PO neurons,78,79 also see ref. 80. Recently, we demonstrated
that spontaneous firing rates and somatosensory evoked responses of ZI neurons are lower inanimals with spinal cord injury compared to sham-operated controls.39 These findings led us
to hypothesize that abnormalities in ZI are casually related to the development ofhyperalgesia in animals with spinal cord lesions (Fig. 2). Indeed, and consistent with thishypothesis, electrical stimulation of ZI ameliorates the hyperalgesia in rats with spinal cordlesions.81 The suppressed activity of ZI is associated with a robust enhanced spontaneousand evoked activity in PO (Fig. 3)39 and S1.82 In PO, neurons recorded from animals withhyperalgesia exhibit a 30-fold increase in spontaneous firing rates and significantly greater
responses to noxious and innocuous stimuli applied to the hindpaw (Fig. 4). PO neurons
respond at the same mechanical threshold that elicit hindpaw withdrawal in animals withspinal cord lesions. Further, the changes in PO activity are not associated with increased
afferent drive from spinal inputs.39 These findings led us to conclude that ZI plays animportant role in regulating nociceptive transmission from PO to S1 and that abnormalities
in ZI are associated with hyperalgesia seen in animals with spinal cord lesions.

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Another source of inhibition in the thalamus that can be affected after spinal cord injury is
the anterior pretectal nucleus (APT). The APT also sends dense GABAergic inputs tohigher-order thalamic nuclei and like ZI, has been shown to regulate the activity of PO
neurons.83 The APT receives nociceptive inputs through the STT,68,84,85 and have been
implicated in a variety of pain-related functions.69,70 Indeed activity in the APT of animals
with confirmed hyperalgesia following spinal cord injury is abnormal. The firing rate of
APT neurons is increased compared to sham-operated controls. This increase is due to aselective increase in firing of tonic neurons that project to and inhibit ZI and an increase inbursts of fast bursting and slow rhythmic neurons. These findings suggest that APT
regulates ZI inputs to PO and that enhanced APT activity contributes to the hyperalgesia
observed in animals following spinal cord injury.86

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In the rat PO there are no GABAergic interneurons87 and therefore, all GABAergic
inhibition is mediated by extrinsic afferents. Another important source of these afferents inaddition to ZI and APT is the GABAergic reticular nucleus of the thalamus (TRN), which
has been hypothesized to play a role in central pain.88 However, anatomical andelectrophysiological evidence argues against a role for TRN in the pathophysiology ofcentral pain. TRN does not receive ascending sensory inputs, and its major source of
excitatory input is from somatosensory cortex.89 Further, GABAergic terminals in PO thatoriginate from ZI differ from those of TRN origin by their larger size, the presence ofmultiple release sites, and multiple filamentous contacts, all features suggesting that ZI
exerts significantly more potent inhibition upon PO.71,90 Moreover, responses evoked withinnocuous stimuli in ventroposterior thalamus—nuclei that receive inhibition exclusively
from TRN—are unaffected by spinal lesions.39
These findings describe a novel system for the regulation of nociceptive processing in thethalamus, the APT/incerto-thalamic system.39,86 Abnormalities in this system are causally
related to maladaptive plasticity following spinal cord injury and manipulation of thissystem may prove effective in ameliorating chronic neuropathic pain.

POTENTIAL TREATMENTS FOR SPINAL CORD INJURY PAIN
Traditionally treatment options for patients suffering from spinal cord injury pain is limited
to either pharmacological treatments or nonpharmacologic approaches or a combination of
both. A variety of medications have been used for the treatment of spinal cord injury pain
including NSAIDS, opioids, antidepressants, anticonvulsants, NMDA receptor antagonists,
alpha 2-adrenergic agonists and GABA-receptor agonists. However, these medications are
rarely consistently effective, and treatment protocols that produce complete pain relief havenever been established.26,91

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Nonpharmacologic approaches include electrical stimulation of various structures in thecentral nervous system such as the spinal cord, the internal capsule,92 the periaqueductal
gray-periventricular gray complex,93 the somatosensory cortex and the thalamus.94
A potentially effective nonpharmachologic treatment that has been advocated for patientswith chronic neuropathic pain is electrical stimulation of the motor cortex. This method wasintroduced in 1991 for the treatment of central pain95 and since then its use has been
extended for the treatment of several other neuropathic pain conditions.96–98 Motor cortex
stimulation is more effective and more advantageous than stimulating other central nervous
system structures because of the low occurrence of complications,99 the lower propensity tocause seizures,100 and the ability to apply it non-invasively using repetitive transcranial
magnetic stimulation.101

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Pain relief occurs almost immediately after onset of motor cortex stimulation inapproximately 50% of patients and persists after the stimulation has stopped.102,103
However, mixed outcomes and varied success rates are observed.104 The lack of wellcontrolled studies, the diverse approaches employed and lack of understanding of how motor
cortex stimulation results in pain relief have contributed to the mixed outcomes and reduced
the enthusiasm for this potentially effective treatment.
Recently, we used our animal model of spinal cord injury pain to study the effective
parameters of motor cortex stimulation.81 We systematically tested a large parameter spaceof stimulus conditions, an advantage not available in human studies. Motor cortex
stimulation reduced hyperalgesia in a manner that is dependent on stimulation parametersand protocol used. Stimulation at an intensity of 50 µA and frequency of 50 Hz for 30
minutes was most effective at reducing mechanical hyperalgesia in rats bilaterally81 (Fig. 5).

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Using these effective stimulation parameters we were able to further test mechanisms ofpain relief produced by motor cortex stimulation. We discussed above evidence (Fig. 3) that
activity of ZI is suppressed in conditions of spinal cord injury pain. The ZI receives dense
projections from prefrontal motor area including the motor cortex105,106 and, therefore,
reduction in hyperalgesia following motor cortex stimulation could be due to enhanced
activity in ZI. To test this notion, we inactivated ZI with lidocaine injections in animals withspinal cord injury and confirmed hyperaglesia, and then stimulated the motor cortex.
Administration of lidocaine but not saline into ZI reversibly blocked the effects of motor
cortex stimulation.81
These results combined with our earlier findings,39 identify the ZI as a source of inhibition
that can be manipulated to produce pain relief, and describe a novel system that affects
nociceptive transmission within the thalamus through corticothalamic interactions.
Identifying the mechanisms involved in the short- and long-term consequences of motor
cortex stimulation will shift current research and clinical practice paradigms and pave theway towards the development of molecular, pharmacologic and physiologic methods forpermanent pain relief that target these structures.

CONCLUSION

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Spinal cord injury pain is a debilitating condition that affects a large number of patients witha primary lesion or dysfunction in the central nervous system. Despite its discovery over a
century ago, the pathophysiological processes underlying the development and maintenanceof chronic neuropathic pain are poorly understood. Pain can result from suppressed
inhibitory inputs from ZI and APT. The suppressed inhibitory inputs will lead to enhanced
activity in the PO, S1 and any thalamic nucleus that is regulated by ZI/APT. Manipulations
that enhance activity in ZI/APT and rescue inhibition may prove effective in the treatment of
spinal cord injury pain.

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Figure 1.

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Behavioral assessment of spinal-lesioned and sham-operated animals. A) hindpaw (dorsal
surface) mechanical withdrawal thresholds decrease over time and hyperalgesia develops
bilaterally after spinal lesions. B) stimulus-response curves collected before and 14 days
after surgery. All values means ± SE; *, statistically significant difference, P < 0.05.39
Reproduced from Masri R, et al. J Neurophysiol 2009; 102:181–191;39 with permission of
the American Physiological Society.

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Figure 2.

Schematic of our overarching hypothesis: In normal conditions, nociceptive transmission
through PO is regulated by powerful inhibition from ZI. In spinal cord injury pain, ZI
activity is suppressed and activity in PO is enhanced. MCS enhances activity of ZI andrestores inhibition in the thalamus and spinal cord. (Blue represents inhibitory inputs; red:
Excitatory Inputs; line thickness represents connection strength).

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Figure 3.

Suppressed activity of ZI in animals with spinal cord injury. A) Comparison of activity
recorded from a ZI neuron in a sham-operated rat (control) with activity recorded from a rat
with a spinal lesion and behaviorally confirmed hyperalgesia. In the neuron recorded fromthe spinal-lesioned rat the spontaneous firing rate (1.6 Hz) is noticeably lower than in theneuron from the sham-operated rat (12 Hz). The magnitude of evoked responses in the
spinal-lesioned rat (0.04 spikes/stimulus) is also markedly lower than in the sham-operated
control (1.5 spikes/stimulus). B) As a group ZI neurons from spinal-lesioned rats havesignificantly lower spontaneous firing rates (0.29 ± 0.28 Hz vs. 0.80 ± 0.70 Hz in shams, P =0.006), and C) Lower somatosensory evoked responses (1.0 ± 0.7 vs. 1.4 ± 1.3 spikes/
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stimulus in shams, P = 0.04). D) To test if suppressed activity in ZI is causally responsible
for the mechanical hyperalgesia in animals with spinal cord injury, we stimulated ZI using
chronically implanted stimulation electrodes. When we applied mechanical stimuli while
stimulating ZI (intensity: 25 µA, frequency: 50 Hz, pulse duration: 300 µs), withdrawal
thresholds were significantly increased, and typically returned to prelesion levels. ZI
stimulation reversed the hyperalgesia in one or both of the hindpaws (range: 0–80% increasein threshold of hindpaw ipsilateral to the lesion, 25–93% increase contralaterally; P < 0.05,
MWU).39 Reproduced from Masri R, et al. J Neurophysiol 2009; 102:181–191;39 withpermission of the American Physiological Society.

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Figure 4.

Enhanced activity of PO in animals with spinal cord injury. A) Representative example ofresponses recorded from a PO neuron in an animal with spinal cord lesion and confirmed
hyperalgesia. Time stamps of action potentials (upper trace) recorded during spontaneous
activity, and during application mechanical forces (lower trace) to the dorsal surface of thehindpaw, using an electronic anesthesiometer. B) In a PO neuron from a sham-operated
control, spontaneous firing rate is low, and responses significantly exceed this spontaneous
activity level only when strong stimuli (>180 g) are applied. In a neuron from the spinallesioned animal with hyperalgesia, spontaneous activity is higher, and electrophysiologicalthresholds are considerably lower (60 g). C) Group data showing that the activity of PO
neurons is significantly higher in animals with spinal cord injury in response to mechanicalhindpaw stimulation. D) The activity of PO neurons in animals with spinal cord injury is
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also higher in response to innocuous stimulation. PSTHs (bin = 1 msec) computed for PO
neurons recorded from a sham-operated and a spinal-lesioned animal. Spontaneous activity(E) and evoked activity (F) are enhanced in PO neurons recorded from spinal-lesioned
animals. *, statistically significant difference, P < 0.05.39 Reproduced from Masri R, et al. J
Neurophysiol 2009; 102:181–191;39 with permission of the American Physiological Society.

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Figure 5.

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Motor cortex stimulation relieves hyperalgesia in animals with spinal cord lesions. A)
Mechanical thresholds (tested on the dorsal surface) of animals with confirmed hyperalgesia
after spinal cord lesions increased following motor cortex stimulation (50 µA, 50 Hz, for 30
minutes) on both hindpaws. Thermal withdrawal latencies to heat (B) and cold (C) stimuli
were also increased in the same animals after motor cortex stimulation. Ipsilateral orcontralateral are relative to the site of spinal lesion. Error bars = SEM.

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Table 1

Animal models of spinal cord injury pain

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Animal Model

Animal Species

MethodBehavioral Findings

Characteristics

Anterolateral cut model36,37,107

Monkey, rat

Anterolateral cutof the spinal cord
to interrupt the
STT

Over grooming andbelow-level bilateral
hyperalgesia to electricaland mechanicalstimulation-

Injury to the STT whichis thought to benecessary for thedevelopment of central
pain-Well characterized
behaviorally-

Mimics clinical injury-

Associated with large
variability in extent oflesion andpathophysiologicalconsequences-

cannot be used to study
below level pain because
hindlimbs areprofoundly affected bylesion-Electrophysiological andmolecular consequences
are well characterized

Contusion model27–29,108

Hemisection model34,35

Rat

Rat

Dropping of aweight on thedorsal aspect of
the spinal cord

Eighty percent ofanimals develop at-level
and above-levelmechanical and thermal
hyperalgesia

Unilateral cut of
the spinal cord at
the mid thoracic
level

All animals develop
bilateral below- andabove-level bilateralmechanical and thermal
hyperalgesia-

Extensive cut to thespinal cord-

Offers little advantage
over the anterolateral
section model

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Quisqualate model32,33

Rat

Injection ofneurotoxic
chemicals into thedorsal horn

Fifty percent of theanimals develop overgrooming in areas
somatotopically related
to the lesion and at- andbelow-level mechanicalhyperalgesia-

High variability inextent of lesion andbehavioral consequences

Ischemia model30,31

Rat

Injecting a photosensitive dye
throughcirculation andusing a focusedlaser beam toregion of the
spinal cord. Theinteraction of thelaser beam withthe photosensitive
dye results in alesion in the graymatter of the
spinal cord

Forty four percent ofanimals develop at-leveland below levelmechanical allodynia.
None of the animals
develop thermal
hyperalgesia-

High variability inextent of lesion andbehavioral consequences

Discrete avulsion of dorsal
roots109

Rat

Unilateralavulsion of T13
and L1 dorsal
root damaging
Lissauer’s tract,
dorsal horn anddorsal column

Bilateral below-levelmechanical hyperalgesia-

Localized injury to thedorsal horn-

Injury is not limited tothe central nervous
systemLocalized
electrolytic
lesions of the

Ninety four percent ofanimals develop
bilateral below- and-Discrete localized lesionin the STTElectrolytic lesions model39,40,82

Rat

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Animal Model

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Animal Species

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MethodBehavioral Findings

Characteristics

anterolateral
quadrant of the
spinal cord

above-level mechanicaland thermal
hyperalgesia-

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Low morbidity and noloss of function
following surgery