Gabapentin suppresses spasticity in the spinal cord–injured rat

• Published in: Neuroscience Vol. 149; no. 4; pp. 813 - 821
• Main Authors: Kitzman, P.H, Uhl, T.L, Dwyer, M.K
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 23.11.2007; Elsevier
• Subjects: Amines - pharmacology; Analysis of Variance; Animals; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Behavior, Animal - drug effects; Biological and medical sciences; Cross-Over Studies; Cyclohexanecarboxylic Acids - pharmacology; Disease Models, Animal; Electromyography - methods; Female; Fundamental and applied biological sciences. Psychology; gamma-Aminobutyric Acid - pharmacology; Medical sciences; muscle hyperreflexia; Muscle Spasticity - etiology; Neurology; Neuropharmacology; Pharmacology. Drug treatments; presynaptic glutamate inhibition; Rats; Rats, Sprague-Dawley; Reflex, Abnormal - drug effects; Spinal Cord Injuries - complications; Time Factors; Vertebrates: nervous system and sense organs; PRE; C-S; root mean square; C-GBP; SCI-S; spinal cord–injured animal receiving saline; muscle hyperreflexia; analysis of variance; GBP; MA; ANOVA; SCI-GBP; VGLUT2; spinal cord injured animal receiving gabapentin; spinal cord injury/injured; presynaptic glutamate inhibition; pre-solution; EMG; vesicular glutamate transporter 2; control animal receiving gabapentin; control animal receiving saline; maximal amplitude; percent of the maximal amplitude; electromyography/electromyographic; gabapentin; SCI; RMS; Spinal cord; Gabapentin; Rat; Rodentia; Central nervous system; Presynaptic inhibition; Anticonvulsant; Glutamate; Vertebrata; Mammalia; Animal; Excitatory aminoacid; Neurotransmitter; Muscle
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.07.020

Abstract Spasticity poses a major detrimental impact on the quality of life in a significant number of people with spinal cord injury (SCI). Recent observations in our laboratory suggest that spinal transection at the sacral S2 level induces a significant increase in glutamatergic input to sacrocaudal motoneurons during the time spasticity is present in the tail muscles. The present study examined the efficacy of gabapentin, an agent that has been shown to reduce glutamate release, in managing spasticity within the tail musculature. Method In this blinded, crossover study adult Sprague-Dawley rats with S2 spinal transections were tested behaviorally for the progression of spasticity in the tail musculature using our established system. When the animals demonstrated a significant level of spastic behavior (e.g. increased response to quick stretch, noxious and non-noxious cutaneous stimuli), they received either saline or the antiepileptic agent gabapentin (GBP; 50 mg/kg i.p.) and were assessed behaviorally and electrophysiologically at 1, 3, 6, 12 and 24 h post-injection. Results Both spastic behavior and electromyography (EMG) activity were significantly decreased at 1 and 3 h post-GBP injection when compared with the activity level following administration of saline. Spastic behavior and EMG activity gradually increased over time and returned to baseline activity by 24 h post-injection. Conclusion Gabapentin diminishes both the behavioral and electrophysiological manifestation of SCI-induced spasticity, in the tail musculature, in a time dependent manner.