The intervertebral disc is a cartilaginous structure that resembles articular cartilage in its biochemistry, but morphologically it is clearly different. It shows degenerative and ageing changes earlier than does any other connective tissue in the body. It is believed to be important clinically because there is an association of disc degeneration with back pain. Current treatments are predominantly conservative or, less commonly, surgical; in many cases there is no clear diagnosis and therapy is considered inadequate. New developments, such as genetic and biological approaches, may allow better diagnosis and treatments in the future.

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Degeneration of the intervertebral disc

The neurotrophin family of neurotrophic factors are well-known for their effects on neuronal survival and growth. Over the past decade, considerable evidence has accumulated from both humans and animals that one neurotrophin, nerve growth factor (NGF), is a peripheral pain mediator, particularly in inflammatory pain states. NGF is upregulated in a wide variety of inflammatory conditions, and NGFneutralizing molecules are effective analgesic agents in many models of persistent pain. Such molecules are now being evaluated in clinical trials. NGF regulates the expression of a second neurotrophin, brain-derived neurotrophic factor (BDNF), in nociceptors. BDNF is released when nociceptors are activated, and it acts as a central modulator of pain. The chapter reviews the evidence for these roles (and briefly the effects of other neurotrophins), the range of conditions under which they act, and their mechanism of action.

Neurotrophins: Mediators and Modulators of Pain

The possible involvement of p38 mitogen-activated protein kinase activation in spinal cord and dorsal root ganglion (DRG) cells in the development of peripheral neuropathic pain has been explored. Ligation of the L5 spinal nerve (SNL) on one side in adult rats produces an early onset and long-lasting mechanical allodynia. This lesion results in activation of p38 in the L5 segment of the spinal cord, most prominently in the ipsilateral dorsal horn, starting soon after the lesion ( 3 weeks. The activated p38 in the spinal cord is restricted entirely to microglia; phospho-p38 colocalizes only with the microglial marker OX-42 and not with either the neuronal marker neuronal-specific nuclear protein or the astrocyte marker GFAP. In contrast, SNL induces a delayed (>3 d) activation of p38 in the L5 DRG that occurs predominantly in neurons. Continuous injection of the p38 inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) via the intrathecal route, starting before the SNL surgery, reduces SNL-induced mechanical allodynia from day 1 to day 10, with maximal effects at early time points. Post-treatment with SB203580 starting on day 1 or on day 10 after surgery also reduces established mechanical allodynia. Because the reduction in neuropathic pain by p38 inhibition occurs before the appearance of p38 activation in DRG neurons, p38 activation in spinal cord microglia is likely to have a substantial role in the earliest phase of neuropathic pain. Coactivation of p38 in DRG neurons and spinal microglia may contribute to later phases of neuropathic pain.

https://www.jneurosci.org/content/jneuro/23/10/4017.full.pdf

p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain

Neural plasticity after peripheral nerve injury and regeneration.

The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis

Activating Transcription Factor 3 (ATF3) Induction by Axotomy in Sensory and Motoneurons: A Novel Neuronal Marker of Nerve Injury

Study Design. The authors retrospectively analyzed the prevalence and features of neck and shoulder pain (axial symptoms) after anterior interbody fusion and laminoplasty in patients with cervical spondylotic myelopathy. Objectives. To reveal the difference in prevalence of postoperative axial symptoms between anterior interbody fusion and laminoplasty and to clarify the pathogenesis of axial symptoms after laminoplasty. Summary of Background Data. Out come of the cervical surgery is evaluated on neurologic status alone; axial symptoms after laminoplasty rarely have been investigated. Such symptoms, however, are often severe enough to interfere with a person's daily activity. Methods. Ninety-eight patients had surgery for their disability secondary to cervical spondylotic myelopathy. Of those patients, 72 had laminoplasty, and 26 had anterior interbody fusion. The presence or absence of axial symptoms was investigated before and after surgery. The duration, severity, and laterality of symptoms were also recorded. Results. The prevalence of postoperative axial symptoms was significantly higher after laminoplasty than after anterior fusion (60% vs. 19%; P<0.05). In 18 patients (25%) form the laminoplasty group, the chief complaints after surgery were related to axial symptoms for more than 3 months, whereas in the anterior fusion groupo, no patient reported having such severe pain after surgery. Conclusions. The prevalence and severity of axial symptoms after laminoplasty proved to be higher and more serious than has been believed. Such symptoms should be considered in the evaluation of the outcome of cervical spinal surgery.

Neck and shoulder pain after laminoplasty. A noticeable complication.

Study Design. The inter and intraobservet reliabilities of an assessment scale for cervical compression myelopathy were exarnined statistically. This scoring system consiats of seven categories motor function of fingers shoulder and elbow, and lower extremity; sensory function of upper extrernity, trunk and lower extremay, and function of the bladder, It evaluates the severity of myelopathy by allocating points based on degree of dysfunction in each cetegory. Objectives. To determine the inter- and intraobserver reliabilities of the revised scoring system (17 - 2 points) for ceryical compression myelopathy proposed by the Japainese Orthopedic Association of Background Dats, Several scales to as sess clinical outcome from treatment of cervical compression myelopathy have been proposed, Most of these scales include items evaluated by observers. However, no syatem, including the Japanese Orthopedic Association scoring systern, has yet been validsted in terms of interethods. From five different university hospitats, 10 spine surgery specialista, 10 orthopedic surgeons who had just passed the board examination of the Japanese had just passed the board examination of the Japanese Orthopedic Association, and 13 residents in the first or second year of orthopedic residency programs were chosen. The participants in this study were 29 patients with myelopathy secondary to ossilication of the posterior longitudinal ligament selected from five perticipating university hospitals, Several surgeons interviewed each patient twice at intervals of 1 to 6 weeks. Inter- and intraobserver reliabilities of the total score for all categories were evaluated by the intreclass correlation coefficient. The extension of the kappe coefficient of Kraemer also was calculated for each category to assess reliability of multivariate ategorical data Results. The interobserver reliability of the total score for the first interview lintzaciass correlation coefficient 0.013) and the intra- and interobserver reliabilities of the total score (intraclass correlation coefficient - 0.826) were high. The revel of experience and the hospital slightly affected the reliability of the Japanese Orthopedic Assoaffected the reliability of the Japanese Orthopedic Association scoring syssem. The kappa values for intraobserverdata generally were high in each category, where asthe kappe values for interobserver data were relatively low for the categories of shoulder-elbow motor function and lower extremity sensory function. Conclusions. The inter- and intraobseriver reliabilities of the Japanese Orthopedic Association scoring system for corvical myelopathy were high, suggesting that this system is useful for assessment of cervical myelopathy in comperative studies of treatment.

Interobserver and Intraobserver Reliability of the Japanese Orthopaedic Association Scoring System for Evaluation of Cervical Compression Myelopathy

STUDY DESIGN A retrospective study was conducted. OBJECTIVE To compare the long-term outcomes of subtotal corpectomy and laminoplasty for multilevel cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA No study has compared the long-term outcomes between subtotal corpectomy and laminoplasty for multilevel cervical spondylotic myelopathy. METHODS In this study, 23 patients treated with subtotal corpectomy and 24 patients treated with laminoplasty were followed up for 10 to 14 years after surgery. Neurologic recovery, late deterioration, axial pain, radiographic results (degenerative changes at adjacent levels, alignment, and range of motion of the cervical spine), and surgical complications were compared between the two groups. RESULTS No significant difference in neurologic recovery was found between the two groups 1 and 5 years after surgery, or at the latest follow-up assessment. Neurologic status deteriorated in one patient of the subtotal corpectomy group because of adjacent degeneration, and in one patient of the laminoplasty group because of hyperextension injury. Axial pain was observed in 15% of the corpectomy group and in 40% of the laminoplasty group (P < 0.05). In the corpectomy group, listhesis exceeding 2 mm developed at 38% of the upper adjacent levels, and osteophyte formation at 54% of the lower adjacent levels. In the laminoplasty group, kyphotic deformity developed in one patient (6%) after surgery. In the corpectomy group, the mean vertebral range of motion had decreased from 39.4 degrees to 19.2 degrees (49%) by the final follow-up assessment. In the laminoplasty group, the mean vertebral range of motion had decreased from 40.2 degrees to 11.6 degrees (29%) by the final follow-up assessment. Neurologic complications related to the surgery occurred in two patients (one myelopathy from bone graft dislodgement and one C5 root palsy from bone graft fracture) of the corpectomy group and four patients (C5 root palsy) of the laminoplasty group. All of these patients recovered over time. The corpectomy group needed longer operative time (P < 0.001) and tended to have more blood loss (P = 0.24). Six patients in the corpectomy group needed posterior interspinous wiring because of pseudarthrosis. CONCLUSIONS Subtotal corpectomy and laminoplasty showed an identical effect from a surgical treatment for multilevel cervical spondylotic myelopathy. These neurologic recoveries usually last more than 10 years. In the subtotal corpectomy group, the disadvantages were longer surgical time, more blood loss, and pseudarthrosis. In the laminoplasty group, axial pain occurred frequently, and the range of motion was reduced severely.

Subtotal corpectomy versus laminoplasty for multilevel cervical spondylotic myelopathy: a long-term follow-up study over 10 years.

Object. The authors report the long-term (more than 10-year) results of cervical laminoplasty for ossification of the posterior longitudinal ligament (OPLL) of the cervical spine as well as the factors affecting long-term postoperative course. Methods. The authors reviewed data obtained in 92 patients who underwent cervical laminoplasty between 1982 and 1990. Three patients were lost to follow up, 25 patients died within 10 years of surgery, and 64 patients were followed for more than 10 years. Results were assessed using the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy. The recovery rate was calculated using the Hirabayashi method. The mean neurological recovery rate during the first 10 years after surgery was 64%, which declined to 60% at the last follow-up examination (mean follow up 12.2 years). Late neurological deterioration occurred in eight patients (14%) from 5 to 15 years after surgery. The most frequent causes of late deterioration were degenerative lumbar disea...

Long-term results of expansive laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine: more than 10 years follow up

Kazuo Yonenobu

Papers

Activating Transcription Factor 3 (ATF3) Induction by Axotomy in Sensory and Motoneurons: A Novel Neuronal Marker of Nerve Injury

Neck and shoulder pain after laminoplasty. A noticeable complication.

Interobserver and Intraobserver Reliability of the Japanese Orthopaedic Association Scoring System for Evaluation of Cervical Compression Myelopathy

Subtotal corpectomy versus laminoplasty for multilevel cervical spondylotic myelopathy: a long-term follow-up study over 10 years.

Long-term results of expansive laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine: more than 10 years follow up