山内 かづ代

STUDY DESIGN: Assessment of pain-related behavior and immunohistology of the dorsal root ganglion in a rat model. OBJECTIVE: To investigate pain-related behavior in a rat model of nerve crush plus inflammation using the CatWalk system. SUMMARY OF BACKGROUND DATA: A definitive method for evaluating animal models of lumbar disease has not been established. Von Frey testing has often been used in this type of study, but the reliability remains in question. The CatWalk system is a computer-assisted apparatus for analyzing gait that provides an automated way to assess gait function during pain. However, there have been few reports using this system for models of lumbar disease. METHODS: Fourteen rats were divided into 2 groups: a treatment group and a sham group. For the treatment group, nucleus pulposus was applied to the sciatic nerve and the sciatic nerve was pinched. Two different methods for assessment of pain-related behavior, von Frey testing and CatWalk analysis, were used before surgery and at 4 and 7 days after surgery. Immunohistochemistry was used to examine calcitonin gene-related peptide expression in L4 to L6 dorsal root ganglia. RESULTS: No significant differences were found between the treatment and sham control groups using von Frey testing. However, significant differences in 4 parameters were found between the 2 groups using the CatWalk system (P < 0.05). The proportion of calcitonin gene-related peptide-immunoreactive neurons was higher in the treatment group than in the control group (P < 0.05). CONCLUSION: Our results demonstrate that the CatWalk system is useful for the measurement of pain-related behavioral change in our rat model in which nociception was indicated at a cellular level. Although further studies are needed, we think that this system is a valid alternative method for the evaluation of models of lumbar disease in rodents.

PURPOSE: The pathological mechanism of lumbar spinal stenosis is reduced blood flow in nerve roots and degeneration of nerve roots. Exercise and prostaglandin E1 is used for patients with peripheral arterial disease to increase capillary flow around the main artery and improve symptoms; however, the ankle-brachial index (ABI), an estimation of blood flow in the main artery in the leg, does not change after treatment. Lumbar spinal nerve roots contain somatosensory, somatomotor, and unmyelinated autonomic nerves. Improved blood flow by medication with prostaglandin E1 and decompression surgery in these spinal nerve roots may improve the function of nerve fibers innervating muscle, capillary, and main vessels in the lower leg, resulting in an increased ABI. The purpose of the study was to examine whether these treatments can improve ABI. MATERIALS AND METHODS: One hundred and seven patients who received conservative treatment such as exercise and medication (n=56) or surgical treatment (n=51) were included. Low back pain and leg pain scores, walking distance, and ABI were measured before treatment and after 3 months of conservative treatment alone or surgical treatment followed by conservative treatment. RESULTS: Low back pain, leg pain, and walking distance significantly improved after both treatments (p<0.05). ABI significantly increased in each group (p<0.05). CONCLUSION: This is the first investigation of changes in ABI after treatment in patients with lumbar spinal stenosis. Improvement of the spinal nerve roots by medication and decompression surgery may improve the supply of blood flow to the lower leg in patients with lumbar spinal stenosis.

BACKGROUND: Our purpose was to examine platelet-rich plasma (PRP) for its effect on bone formation and to follow the immunohistochemical changes in calcitonin gene-related peptide (CGRP) in dorsal root ganglion neurons innervating the discs as a possible index of nociceptive nerve transmission in a rat model. METHODS: A total of seventy rats were used. Ten constituted a non-punctured disc sham group, while another ten rats constituted a group that underwent puncture of the L4-L5 discs. Forty rats were in experimental groups in which the L4-L5 discs were punctured; posterolateral lumbar arthrodesis was performed with PRP (the PRP group) or without the use of PRP (the normal arthrodesis group), with twenty rats in each group. The remaining ten rats were used as blood donors. Four and eight weeks after surgery, microcomputed tomography examinations were done to evaluate the amount of bone and the L4-L5 spines were harvested to evaluate bone union, followed by resection of dorsal root ganglion neurons. The percentages of Fluoro-Gold-labeled and CGRP-immunoreactive neurons were calculated. RESULTS: The platelet count and the concentration of growth factors in PRP were higher than those in blood (p &lt; 0.05). The bone volumes observed in the PRP group were significantly greater than those of the normal arthrodesis group at four and eight weeks (p &lt; 0.05). Three (30%; 95% confidence interval [CI], 6% to 65%) of ten rats in the normal arthrodesis group and eight (80%; 95% CI, 44% to 98%) of ten rats in the PRP group were considered to have bone fusion four weeks after surgery (p &lt; 0.05). At eight weeks, seven (70%; 95% CI, 34% to 94%) of ten rats in the normal arthrodesis group and nine (90%; 95% CI, 55% to 99%) of ten rats in the PRP group were considered to have bone fusion (p = 0.27). The proportion of CGRP-immunoreactive neurons was significantly greater in the punctured group than in the other groups. There were no significant differences between the normal arthrodesis group and the PRP group. CONCLUSIONS: PRP appears to promote bone formation in rats and has a tendency to shorten the period of bone union in this rat model of posterolateral lumbar arthrodesis, but it did not influence the proportion of CGRP-immunoreactive neurons, a likely indicator of inflammatory pain originating from the degenerative intervertebral disc. CLINICAL RELEVANCE: The ability of PRP in this model suggests that it may be able to shorten the period of union and lead to an early return to social activities after treatment.

PURPOSE: To evaluate L5 nerve root injuries caused by outwardly misplaced S1 pedicle screws. Pedicle screws remain the criterion standard for fixation of L5-S1 to correct lumbosacral instability. When inserting S1 pedicle screws, it is possible to injure the L5 nerve root if screws are inserted outwardly and the tip of the screw perforates the anterior cortex of the sacrum. Despite this risk, to our knowledge this type of injury has never been reported as a case series. METHODS: We experienced 2 cases of L5 nerve root injury caused by outwardly-inserted S1 pedicle screws. In both cases, bilateral S1 pedicle screws were inserted outwardly using a free-hand technique, and on one side, screws induced severe pain by impinging on an L5 root. Computed tomography after the selective rootgraphy of the injured nerve showed the nerve compressed laterally by screw threads in Case 1 and crushed between the screw threads and the sacral body in Case 2. RESULTS: In both cases, leg pain disappeared immediately after the infiltration of the nerve with lidocaine, but symptoms recurred within a few days in Case 1 and within an hour in Case 2. Conservative treatment of three spinal nerve infiltrations was effective in Case 1, but reinsertion of the rogue screw was necessary in Case 2. CONCLUSIONS: Surgeons should recognize that lateral inclination of S1 pedicle screws can cause L5 nerve root injury, which may require reinsertion of the screw, especially in cases where insertion is difficult because of overlapping surrounding muscle or bony tissue.

STUDY DESIGN: Prospective study. OBJECTIVE: To examine the efficacy of teriparatide or bisphosphonate treatment to reduce pedicle screw (PS) loosening after instrumented lumbar posterolateral fusion in postmenopausal women with osteoporosis. SUMMARY OF BACKGROUND DATA: Failure of fixation caused by loosening of PSs in osteoporosis is a problem in spinal surgery. Oral administration of bisphosphonate or intermittent injection of parathyroid hormone treatment increases bone mass and reduces the risk of osteoporotic vertebral fractures. Although these treatments may be factor in improving bone quality, a clinical study of the efficacy of bisphosphonate or parathyroid hormone for reducing PS loosening that addresses the quality of the bone marrow and pedicle cortex has not yet been reported. METHODS: Sixty-two women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 3 groups: a teriparatide group (daily subcutaneous injection of 20 μg of teriparatide, n = 20), a bisphosphonate group (daily oral administration 2.5 mg of risedronate, n = 20), and a control group (without medication for osteoporosis, n = 22). All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft. Loosening of PSs and surgical outcome were evaluated radiographically, clinically, and by computed tomography 12 months after surgery. RESULTS: At 12-month follow-up, the incidence of PS loosening was 7% to 13% in the teriparatide group, 13% to 26% in the risedronate group, and 15% to 25% in the control group. The incidence of PS loosening in the teriparatide group was significantly lower than that in the risedronate or the control group (P < 0.05). In contrast, the extent of PS loosening in the risedronate group was not significantly different from that in the control group (P > 0.05). CONCLUSION: Our findings suggest that administration of teriparatide increased the quality of the lumbar spine bone marrow and pedicle cortex.

Trophic support and myelination of axons by Schwann cells in the PNS are essential for normal nerve function. Herein, we show that deletion of the LDL receptor-related protein-1 (LRP1) gene in Schwann cells (scLRP1(-/-)) induces abnormalities in axon myelination and in ensheathment of axons by nonmyelinating Schwann cells in Remak bundles. These anatomical changes in the PNS were associated with mechanical allodynia, even in the absence of nerve injury. In response to crush injury, sciatic nerves in scLRP1(-/-) mice showed accelerated degeneration and Schwann cell death. Remyelinated axons were evident 20 d after crush injury in control mice, yet were largely absent in scLRP1(-/-) mice. In the partial nerve ligation model, scLRP1(-/-) mice demonstrated significantly increased and sustained mechanical allodynia and loss of motor function. Evidence for central sensitization in pain processing included increased p38MAPK activation and activation of microglia in the spinal cord. These studies identify LRP1 as an essential mediator of normal Schwann cell-axonal interactions and as a pivotal regulator of the Schwann cell response to PNS injury in vivo. Mice in which LRP1 is deficient in Schwann cells represent a model for studying how abnormalities in Schwann cell physiology may facilitate and sustain chronic pain.

STUDY DESIGN: Immunohistochemistry for tumor necrosis factor (TNF)-α in nucleus pulposus of adolescent patients with lumbar disc herniation. OBJECTIVE: To examine whether an inflammatory cytokine is expressed in the nucleus pulposus of adolescent patients with lumbar disc herniation. SUMMARY OF BACKGROUND DATA: TNFα is thought to play a crucial role in the radicular pain caused by lumbar disc herniation in adult patients. However, the expression of TNFα in the nucleus pulposus of adolescent patients with lumbar disc herniation has not been explored. METHODS: Five samples of nucleus pulposus from adolescent patients with lumbar disc herniation (age, 12-16 yr; n = 5) or controls requiring surgery for other back problems (age, 12-16 yr; n = 4; nonpainful scoliosis) were harvested during surgery. Nucleus pulposus specimens were immunostained using TNFα antibodies and immunostained cells in the nucleus pulposus were counted. We compared the expression of TNFα between the 2 groups. RESULTS: In patients with lumbar disc herniation, more TNFα-immunoreactive cells were seen in the nucleus pulposus in comparison with patients with nonpainful scoliosis (P < 0.01). CONCLUSION: The results suggest that TNFα may play a role in adolescent patients with lumbar disc herniation. The TNFα expression may be related with disc degeneration and pain in adolescent patients with lumbar disc herniation.

A 26-year-old paraplegic schizophrenic Japanese woman suffered from severe kyphosis and back pain derived from lumbar burst fractures caused by jumping. She had already undergone resection of the L1 and L2 spinous processes for sharp angular kyphosis, but she still had severe kyphosis and back pain at the L1 and L2. Radiographical examination revealed fused anterior columns at L1 and L2 with severe local kyphosis and a significantly decreased percutaneous distance in the back. The patient underwent anterior instrumented bony resection including an L2 vertebral osteotomy: bilateral L2-L3 facetectomy and partial posterior osteotomy of the L2 vertebrae via a posterior approach followed by an anterior corpectomy of the L2 vertebrae and insertion of a cylindrical cage. No posterior instrumentation was used owing to the presence of atrophied paraspinal soft tissues. Lumbar interbody fusion was performed with vertebral body screws extending from T12 to L4 and corresponding anterior distension and posterior compression. The procedure corrected the kyphosis by 15° and enhanced local stability. Postsurgical visual analogue scale improved from 9.0 to 2.0 and Oswestry Disability Index from 40 to 17.8, respectively. In conclusion, we have demonstrated that anterolateral interbody fusion using extended fixation can compensate for posterior corrective surgery.