Model of neuropathic intermittent claudication in the rat: methodology and application.
In the present study we characterize a rat neurogenic intermittent claudication model which was accomplished by placing two pieces of silicone rubber of various sizes into the lumbar (L4 and L6) epidural space. After induction of spinal stenosis walking function was measured using a treadmill apparatus and sensory functions were tested by measuring thermal and tactile withdrawal threshold (von Frey filaments) for the period of 28 days after stenosis. In addition, local spinal cord blood flow (SCBF) was measured, periodically, before and after induction of stenosis using laser Doppler. After implantation of two pieces of silicone rubber (width 1.25 mm, height 1.0 mm, length 4.0 mm) a significant running dysfunction, as evidenced by shortening of running distance, was measured as soon as 24 h after stenosis (178.5+/-59.1 m vs 681.3+/-70.2 m). This effect persisted for 28 days after surgery. Similarly, a significant tactile (but not thermal) hypersensitivity was measured for a period of 28 days (1.2+/-0.3 g vs 14.9+/-0.2 g). In this experimental group the measurement of local SCBF revealed a significant (30-50%) reduction in the territory of spinal stenosis measured at 3,7,14 or 28 days after surgery. Implantation of larger pieces of silicon rubber (1.5 mm width) caused a significant increase in the incidence of urinary retention and mortality rate. These data show that chronic partial spinal compression at L4 and L6 spinal level lead to the development of significant motor/sensory dysfunction which resemble those seen in patients with neurogenic intermittent claudication. The lack of motor dysfunction under resting conditions but its appearance during forced exercise also suggest that the development of local spinal ischemia can represent one of the mechanisms.
Takenobu
Y
Y
Minase Research Institute, Discovery Research Laboratories III, Ono Pharmaceutical Co. Ltd, 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618, Japan.
Katsube
N
N
Marsala
M
M
Kondo
K
K
D000818:Animals; D002420:Cauda Equina / Q000503:physiopathology; D004195:Disease Models, Animal; D005080:Exercise Test; D005106:Exploratory Behavior / Q000502:physiology; D007383:Intermittent Claudication / Q000503:physiopathology*; D008124:Locomotion / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009408:Nerve Compression Syndromes / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012420:Running / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology; D013116:Spinal Cord / Q000098:blood supply; D013130:Spinal Stenosis / Q000503:physiopathology; D014110:Touch / Q000502:physiology