An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat
San-Jue Hu* and Jun-Ling Xing
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Institute of Neuroscience, The Fourth Military Medical University, The Sixth Clinical Center of CASP, Xi'an 710032, PR China

Received 7 August 1996; revised 17 March 1998; accepted 27 March 1998. Available online 9 September 1998.
Abstract
Under anesthesia and sterile surgery, a small stainless steel rod (4 mm in length and 0.5–0.8 mm in diameter) was inserted into the L5 intervertebral foramen in the rat, developing intervertebral foramen stenosis and hence producing a chronic steady compression of the dorsal root ganglion (DRG). The hind paw on the injured side exhibited a significant reduction
in the latency of foot withdrawal to noxious heat and manifested a persistent heat hyperalgesia 5–35 days after surgery. Injection of 1% carrageenan into the intervertebral foramen, presumably causing inflammation of the DRG, also produced hyperalgesia to heat on the hind paw of the injured side 5–21 days after surgery. Extracellular electrophysiological recordings from myelinated dorsal root fibers were performed in vivo. Spontaneous activity was present in 21.5% of the fibers recorded from DRG neurons injured with chronic compression in contrast to 1.98% from uninjured DRG neurons. The pattern of spontaneous activity was periodic and bursting in 75.3% of the spontaneously active fibers. These neurons had a greatly enhanced sensitivity to mechanical stimulation of the injured DRG and a prolonged after discharge. In response to TEA, topically applied to the DRG, excitatory responses were evoked in the injured, but not the uninjured, DRG neurons. Application of this experimental model may further our understanding of the neural mechanisms by which chronic compression of DRG induces low back pain and sciatica.
Author Keywords: Dorsal root ganglion; Chronic compression; Hyperalgesia; Spontaneou
s activity
Index Terms: spinal ganglion; nerve compression; low back pain; ischialgia
Article Outline
1. Introduction
2. Methods
2.1. Animals and surgery
2.2. Measurement of foot withdrawal latencies to noxious heat stimuli
2.3. Surgical exposure of DRG and the method of microfilament recording
2.4. Mechanical stimulation of DRG
2.5. Test of the effects of chemical agents on activity in DRG neurons
3. Results
3.1. Latency of foot withdrawal due to noxious heat
3.2. Incidence of spontaneous activity in neurons with cell bodies in the chronic compressed DRG
3.3. Patterns of spontaneous discharges from the chronic compressed DRG neurons
3.4. Responses of DRG neurons to mechanical stimulation of the ganglion
3.5. Effects of TEA and EGTA on neuronal activity
4. Discussion
Acknowledgements
References
1. Introduction
The chronic compression of the dorsal root ganglion (DRG) or its near nerve roots after vert
ebral injuries, intervertebral disc herniation or intervertebral foramen stenosis is an important factor causing low back pain and sciatica. Animal models designed to investigate the algogenic mechanisms consequent to injuries of the nerve or dorsal root, have employed experimental procedures such as dorsal root irritation or rhizotomy, cauda equina compression, segmental spinal nerve ligation and nerve root irritation (Howe et al., 1977; Wiesenfeld and Lindblom, 1980; Olmarker et al., 1991; Kim and Chung, 1992; Kawakami et al., 1994). However, none of these were aimed at determining the pathophysiological processes resulting from a chronic compression of the DRG.
We present a method of producing a chronic compression of the L5 DRG in rats by inserting a fine stainless steel rod into the L5 intervertebral foramen and thereby producing a stenosis of the intervertebral foramen. The affected hind limb becomes hyperalgesic to noxious heat stimuli and the L5 DRG neurons exhibit persistent spontaneous activity and enhanced responses to certain mechanical and chemical stimuli. We therefore believe that this animal model of a chronic compression of the DRG will increase our understanding of the neural mechanisms of low back pain and sciatica.
2. Methods
2.1. Animals and surgery
Adult (200–350 g) Sprague–Dawley rats of both sexes were used under a University approved protocol. The sterilized surgical procedures were carried out under sodium pentobarbital anesthesia (40 mg/kg, i.p.). The skin was incised on the left side of the lumbar vertebrae between L4 and L6 and the left paraspinal muscles separated from the mammillary process and the transverse process at the L4–L6 level. In the first group of rats (the chronic compression group), the L5 intervertebral foramen was clearly exposed and a fine, L-shaped needle (about 0.6 mm in diameter) inserted about 4 mm into the L5 intervertebral foramen at a 30° angle with respect to the dorsal middle line and 10° with respect to the vertebral horizontal line. When the needle tip reached the DRG, the hind leg muscles of the operated side exhibited a slight, transient twitch. Then, the needle was withdrawn from the L5 intervertebral foramen and a stainless steel rod, 4 mm in length and 0.5–0.8 mm diameter, was inserted into the L5 intervertebral foramen along the path of the
needle. This was intended to produce a steady compression against the L5 DRG (Fig. 1). With the intent of exerting a consistent pressure on the DRG, the diameter of the stainless steel rod was increased in relation to the weight of the rat, such that a diameter of 0.5–0.6 mm was selected for the rats of 200–250 g and diameters of 0.7 and 0.8 mm for rats weighing 250–300 and 300–350 g, respectively. Then the muscular layer and skin were sutured and antibiotics administered. In the second group of rats (the inflammation group), an injection of 15 μl of 1% carrageenan into the region around DRG through the L5 intervertebral foramen produced a local inflammation. In the third group of rats (the acute compression group), a stainless steel rod was inserted into the L5 intervertebral foramen for 30 s and then immediately removed. Lastly, in the fourth group, a sham surgery group of rats, the surgical procedure was identical to that for the chronic compression group, except that the stainless steel rod was not inserted into the interveterbral foramen. Fig1 2.2. Measurement of foot withdrawal latencies to noxious heat stimuli
The rat was placed in an apparatus used to measure the latency of foot withdrawal to noxious heat stimuli (Hargreaves et al., 1988; Yang et al., 1993). A radiant heat source ben
eath the glass floor was focused on a 5 mm diameter spot on the posterior part of the plantar surface of the hind paw. The latency of foot withdrawal to the heat stimulus was measured as described previously. The hind paw on each side was alternately tested at interstimulus intervals of 5 min, five times on each paw. A difference score was calculated by subtracting the average latency of the control side from the average latency of the operated side. A negative difference score indicated a lower threshold at the operated side, i.e. hyperalgesia to noxious heat (Bennett and Xie, 1988).

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