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Neurosurgery:
doi: 10.1227/01.neu.0000395797.74965.ea
Science Times

Gabapentin Reduces Experimental Secondary Neurologic Dysfunction in Rats

Singh, Harry; Wang, Michael Y

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Secondary neurologic dysfunction that develops after chronic spinal cord injury affects approximately 250 000 Americans. The most disabling manifestation resides in spasticity and autonomic dysreflexia, which is often triggered by noxious somatic or visceral stimuli below the level of injury. A common pathway appears to be responsible for inducing these reactions and was the target of pharmacologic therapy designed to decrease their appearance.

In a recent article published in Spinal Cord, Rabchevsky and colleagues studied the effects of Gabapentin therapy in a T4 complete spinal cord transaction rodent model.1 Gabapentin has been shown to inhibit presynaptic glutamate release, and was administered to the rodent models to assess its ability in diminishing the appearance of spasticity and autonomic dysreflexia after application of noxious stimuli.

Twenty one adult female Wistar rats were anesthetized and then given T4 level cord transaction using a scalpel. Two- and 3-week injured rats were then injected with either saline or Gabapentin (50 mg/kg) 1 hour prior to cardiophysiologic measurements in response to colorectal distension (CRD) as well as behavioral assessments in response to tail manipulation. The cardiophysiologic measurements were taken from telemetric pressure transmitters implanted in the rodents' descending aorta 1 week prior to spinal cord injury or from femoral arterial catheterization 2 weeks after cord injury.

Behavioral assessment of tail spasticity was performed between colorectal distension trials. The response of tail muscles to quick stretch, light stroking (non-noxious), and light pinch (noxious) applied 10 cm from tail tip were analyzed. The animals demonstrated either stage 2, stage 3, or stage 4 spasticity before pharmacologic intervention. Quick stretch response was graded using a 5-point scale (Figure 1). Light touch response was graded using a 3-point scale: 0= no response, 1= minimal flexion, 2= pronounce flexion.

Figure 1
Figure 1
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The authors found statistically significant reductions of CRD evoked hypertension in subjects treated with Gabapentin compared to the saline treated rodents. Femoral arterial catheterization demonstrated a more than twofold reduction whereas aortic telemetric monitoring demonstrated an almost threefold reduction in CRD evoked hypertension. Baseline mean arterial pressure (MAP) recordings were not significantly different between groups (Figure 3).

Figure 3
Figure 3
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In 2 week post injury testing, muscle spasticity was significantly reduced (P < .05) in Gabapentin treated subjects to both stretch (non-noxious) and pinch (noxious) stimuli compared to saline treated arm (Figure 2). At 3-week testing, Gabapentin-treated rats demonstrated significantly reduced tail spasticity to both noxious and non-noxious stimuli by at least 80%.

Figure 2
Figure 2
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The study demonstrates positive findings. However, these results were obtained in an animal model. Additionally, the induced spinal cord injury is that of complete transaction, not a contusion model which may be more accurate for comparison to human spinal cord injury.

Gabapentin has been widely used off-label for treatment of neuropathic pain. The findings from this study suggest that Gabapentin administration attenuates 2 additional major sequelae of spinal cord injury. In a patient population that currently consumes numerous medications for treatment of their spinal cord injury, using a single agent for alleviation of multiple symptoms could only benefit both caregivers and patients. However promising these results are, the results are demonstrated in an animal model. Translation of results in human subjects would have to be demonstrated before clinical application could be implemented.

Harry Singh

Michael Y. Wang

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REFERENCE

1. Rabchevsky AG, Patel SP, Duale H, Lyttle TS, O'Dell CR, Kitzman PH. Gabapentin for spasticity and autonomic dysreflexia after severe spinal cord injury. Spinal Cord. 2011;49(1):99-105. Epub 2010 Jun 1.

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