Tsuneo Takebayashi

Effect of Nucleus Pulposus on the Neural Activity of Dorsal Root Ganglion

Study Design. This study was designed to investigate, using neurophysiologic techniques in an in vivo rat model, the effect of application of nucleus pulposus to the nerve root on the neural activity of the dorsal root ganglion and the corresponding receptive fields. Objectives. To assess a further role of the dorsal root ganglion in mechanisms of radicular pain in lumbar disc herniation. Summary of Background Data. It has been suggested that the epidural application of autologous nucleus pulposus without mechanical compression causes nerve root inflammation and related radicular pain in lumbar disc herniation. Concerning the dorsal root ganglion, its mechanical hypersensitivity and potential for generating ectopic discharges have been reported. However, the effect of autologous nucleus pulposus on the dorsal root ganglion is uncertain. Methods. In adult Sprague-Dawley rats spontaneous neural activity was recorded from the surgically exposed L5 dorsal root using electrophysiologic techniques, and the mechanosensitivity of L5 dorsal root ganglia and corresponding receptive fields on the hind paw were measured using calibrated nylon filaments. Autologous nucleus pulposus from the tail or fat was implanted at the L5 nerve root. Neural activity was monitored for 6 hours. Results. Spontaneous neural activity in the nucleus pulposus group gradually increased and showed significant differences compared with the fat group from 2.5 to 6 hours after exposure. The mechanosensitivity of the dorsal root ganglia showed significant increases compared with the fat group. Conclusions. After application of nucleus pulposus to the nerve root, the dorsal root ganglion demonstrated increased excitability and mechanical hypersensitivity. These results suggest that nucleus pulposus causes excitatory changes in the dorsal root ganglion.

An electrophysiologic study of mechanoreceptors in the sacroiliac joint and adjacent tissues.

Study Design. The somatosensory afferent units in the sacroiliac joint of an animal model were investigated using an electrophysiologic technique. Objectives. To identify the mechanosensitive receptive fields in the sacroiliac joint, and to determine their distribution and characteristics. Summary of Background Data. The sacroiliac joint is considered to be a source of lower back pain. Although there have been clinical studies on the diagnosis of sacroiliac joint pain, no satisfactory diagnostic method other than joint blocks has been reported. It still is not clear whether the sacroiliac joints actually transmit pain to the central nervous system. The sensory innervation of the sacroiliac joint has not been fully characterized neurophysiologically. Methods. Experiments were performed on 10 adult cats weighing 2.6 to 4 kg. The animals were anesthetized with intravenous sodium pentobarbital. An L4–L7 laminectomy was performed. The L4–L6 dorsal roots were cut at their proximal ends, split, and draped over a bipolar recording electrode. Glass probes were used to search the sacroiliac joint and adjacent tissues for mechanosensitive units. When units were identified, they were stimulated electrically to obtain conduction velocities and by Semmes-Weinstein monofilaments to determine mechanical thresholds. Results. In the sacroiliac joint and adjacent muscles, 29 discrete mechanosensitive units were identified. Of these 29 units, 26 were found in the posterior sacroiliac ligament and the remaining 3 in the adjacent muscles. Also, 16 units (55%) were identified in the proximal third of the sacroiliac joint. Conduction velocities of the units ranged from 3.1 to 22 m/second (average, 9.2 m/second), and 26 units were group III. Mechanical thresholds of the units ranged from 4.6 to 164.3 g (average, 69.7 g). Whereas 28 units (96.6%) had thresholds higher than 7 g, one unit (3.4%) had a threshold lower than 7 g. Conclusions. Group III units with mechanical thresholds higher than 7 g may serve as nociceptors, and units with thresholds of lower than 7 g may serve as proprioceptors. The current study showed that most of the units in the sacroiliac joint were high-threshold group III units that perhaps had a nociceptive function. This result suggests that the sacroiliac joint may be a source of lower back pain in humans. This study also showed that the sacroiliac joint has little proprioceptive function.

A quantitative analysis of sensory function in lumbar radiculopathy using current perception threshold testing.

Study Design. Peripheral sensory functions in patients with radiculopathy resulting from lumbar disc herniation and in control individuals were analyzed using current perception threshold testing. Objective. To evaluate the severity of sensory disturbance quantitatively in patients with lumbar radiculopathy. Summary of Background Data. Subjective evaluation of the severity of sensory disturbance associated with spinal disorders using conventional methods often is difficult. Current perception threshold evaluation is a recently proposed method for studying peripheral nerve dysfunction. This is a quantitative sensory test for analyzing functions of A-beta, A-delta, and C fibers. Methods. In this study, 48 patients with lumbar radiculopathy resulting from lumbar disc herniation were examined. The mean age of the patients was 37.9 years. All the patients had pain distribution from the compression of one lumbar nerve root (L5 or S1), and unequivocal unilateral disc herniation of the corresponding level was shown by magnetic resonance imaging. Eleven healthy volunteers were used as control subjects. Their mean age was 38.2 years. Current perception threshold evaluation using a Neurometer device was performed at three frequencies: 2000, 250, and 5 Hz. The stimulus sites were located on the dorsal side of the first metatarsus (the L5 dermatome) and the dorsal side of the fifth metatarsus (the S1 dermatome). These sites were investigated on both legs in all the patients and control subjects. The intensity of pain was scored using a visual analog scale. Results. In the control group, there were no significant differences in current perception threshold values at any frequency between the left and right legs. In the patient group, the current perception threshold values in the affected legs were significantly higher than those in the contralateral legs at all frequencies. The current perception threshold values in the affected legs in the patient group were significantly higher than those in the control subjects at 2000 and 250 Hz, whereas there were no significant differences at 5 Hz. The current perception threshold values in the affected legs were significantly higher in patients with hypesthesia than in those without hypesthesia at 2000 and 250 Hz, and in patients with severe pain than in those with less pain at 5 Hz. Conclusions. Current perception threshold testing showed that the functions of A-beta, A-delta, and C fibers deteriorated in patients with lumbar radiculopathy. This technique may be useful for quantifying sensory nerve dysfunction in patients with radiculopathy.

Effects of Nucleus Pulposus on Nerve Root Neural Activity, Mechanosensitivity, Axonal Morphology, and Sodium Channel Expression

Study Design. This study analyzed the effects of autografted nucleus pulposus on nerve root axon morphology, neurophysiologic function, and sodium channel expression. Objectives. To investigate the chronic effects of the epidural implantation of nucleus pulposus on nerve root morphology, neural activity, ectopic discharge, mechanosensitivity, and sodium channel expression. Summary of Background Data. It has been reported that ectopic discharges were recorded antidromically from sural nerve on compressing nucleus pulposus exposed spinal nerves. However, it is not clear what the effects of nucleus pulposus are on ectopic discharges recorded directly from the spinal nerve roots. It is also not clear what the effects of nucleus pulposus are on the threshold pressure to provoke ectopic discharges in the spinal nerves. Sodium channel content increases in remodeling axons after nerve injury, but it is not clear what the effects of nucleus pulposus are on sodium channel expression in spinal nerve. Methods. Forty-six male Sprague-Dawley rats were used, 20 in a nucleus pulposus-implanted group, 18 in a fat-implanted group, and 8 in a normal group. Fresh autografted nucleus pulposus or fat tissue was implanted into the dorsal epidural space at the L4–L5 disc level. On the 7th, 21st, or 42nd day, neurophysiologic recordings were made to determine nerve root response to compression. Nerve roots were then harvested to determine sodium channel protein concentration and histologic changes in the nerve root. The correlations between sodium channel density and neural activity and mechanosensitivity of dorsal root were analyzed statistically. Results. Ectopic discharge rate was higher in nucleus pulposus 7-day group. Threshold pressure to evoke ectopic discharges was lower in the nucleus pulposus 7-day group, and higher in the nucleus pulposus 42-day group compared to the normal group. Sodium channel protein density increased in the nucleus pulposus 7-day and nucleus pulposus 21-day group compared to normal nerve. Sodium channel density changes were not correlated to threshold pressure. Ectopic discharge rate increased with increase of sodium channel density in the nerve roots. The number of axons with neuropathy increased in the nucleus pulposus 7-day and 21-day groups. Conclusions. Acute exposure of nerve root to nucleus pulposus resulted in increased number of axons with neuropathy, higher intensity of ectopic discharges on compression, and nerve mechanosensitization. Chronic exposure resulted in mechanical desensitization. Changes of sodium channel density were correlated to ectopic discharge rate.

MECHANOSENSITIVE AFFERENT UNITS IN THE LATERAL LIGAMENT OF THE ANKLE

We have studied the mechanosensitive afferent units in the lateral ligament of the ankle of the cat, with reference to the causes of lateral instability after injury, using electrophysiological recording from the lumbar dorsal rootlets. We identified 30 mechanosensitive units in the lateral ligament; 28 (93%) were located near the attachment to the fibula and calcaneus, which included both low-threshold group-II units and low- and high-threshold group-III units. Our results indicate that there are both proprioceptors and nociceptors in the lateral ligament of the cat ankle, and confirm that afferent fibres from the lateral ligament may contribute to the stability of the joint by regulation of position and movement.

Electrophysiologic changes in dorsal root ganglion neurons and behavioral changes in a lumbar radiculopathy model.

Study Design. The DRG neuron was electrophysiologically investigated using a rat model with constriction of the proximal site of the DRG. Objectives. To investigate the pathomechanisms of lumbar radiculopathy, we established a rat model with constriction of the proximal site of the DRG. And to characterize the DRG neurons in the rat model of lumbar radiculopathy, the physiologic properties regarding action potential, Na+, and K+ current of the DRG neurons were analyzed through the use of patch clamp recordings. Summary of Background Data. In lumbar root constriction models, properties of secondary afferent neurons in the dorsal horn have been investigated. However, the electrical properties of DRG neuron have not been well investigated. Methods. To compare the excitability of DRG neurons between root constriction models and sham, we examined the threshold current, action potential (AP) threshold, resting membrane potential (RMP), afterhyperpolarization (AHP), action potential duration 50 (APD50), action potential amplitude, maximum rise time of AP, and pattern of discharges evoked by depolarizing current. We also examined the peak Na+ current and steady-state Na+ and K+ currents with the voltage clamp technique. Results. The rats in the root constriction group demonstrated mechanical allodynia and thermal hyperalgesia. In measurement of the action potential, lower threshold current, more depolarized RMP, larger AHP, and prolonged APD50 were measured in the root constriction neurons compared with the sham group. The incidence of sustained burst was significantly higher in root constriction neurons. The Na+ current in root constriction neurons was markedly larger. There were no significant differences in K+ current density and voltage dependency. Conclusions. The constriction of lumbar root increased excitability and Na+ current amplitude of DRG neurons. These findings indicate that lumbar radicular pain may be associated with increased excitability of involved DRG neurons.

Vertebral body ischemia in the posterior spinal artery syndrome: case report and review of the literature.

Study Design. A case of posterior spinal cord syndrome in which magnetic resonance images showed predominant T2 hyperintense signal in the adjacent vertebral body is reported. Objectives. To present the case for abnormal bone marrow magnetic resonance signal in the radiologic diagnosis of posterior spinal cord syndrome and to review its significance. Summary of Background Data. Infarction in the region of posterior spinal arteries has been rarely described. This is attributable not only to the infrequent occurrence of infarction of posterior spinal arteries, but also to a lack of well-established diagnostic procedures. It is of clinical value to define diagnostic images of posterior spinal cord syndrome, especially early in the course of the disease. Methods. The subject was a 52-year-old man who was presented with acute nontraumatic myelopathy. Magnetic resonance imaging, performed serially after onset of the disorder from 5 hours to 11 months, was evaluated in comparison with neurologic findings. The literature was reviewed to discuss the magnetic resonance images of spinal cord infarction. Results. The neurologic findings were consistent with posterior spinal cord syndrome. A magnetic resonance image taken at 5 hours after onset of the syndrome showed T2 hyperintense signal in the T12 vertebral body. At 3 days after onset, T2 hyperintense signal became obvious in the posterior portion of the spinal cord at T9–T12 vertebral levels. Follow-up magnetic resonance imaging at 41 days, 8 months, and 11 months showed a decrease in the size and intensity of the T2 signal change in the spinal cord and T12 vertebral body. In the literature, T2 hyperintense bone marrow signal was defined in one case of posterior spinal cord syndrome and seven cases of anterior spinal cord syndrome. Conclusions. Associated bone marrow abnormalities likely reflect the underlying pathology of the blood supply to the vertebral body, and may be an additional key sign for radiologic diagnosis of posterior spinal cord syndrome.

Diagnostic features of sciatica without lumbar nerve root compression.

Study Design Retrospective case series review of patients showing sciatica without radiographic evidence of nerve root compression. Objective To elucidate clinical features of sciatica caused by extralumbar spinal lesions. Summary of Background Data Sciatica caused by extralumbar spinal lesions has been reported sporadically. Given the paucity of case series studies, however, the pathology and clinical features of such sciatica remain not fully understood. Methods Sixty-one patients who presented with persistent sciatica were examined with lumbar magnetic resonance (MR) imaging. Of these, the records of patients showing no detectable nerve root compression in MR images were reviewed with respect to demographics, neurologic status, further diagnostic procedures, treatments, and treatment outcomes. Results Of 61 patients, 10 (16.4%) showed sciatica and a lack of nerve root compression in the lumbar MR imaging. In demographics, there was female sex dominance (9 patients) and right side preference (9 patients). Eight patients exhibited sensory disturbance beyond a single dermatome. Piriformis syndrome was diagnosed in 3 patients and 5 patients were considered to have sacral plexus pathologies associated with gynecologic conditions such as ectopic endometriosis, ovarian cyst, and pregnancy. A review of the literature also supported the right side preference in sciatica associated with gynecologic conditions. Conclusions Piriformis syndrome and gynecologic conditions account for most cases of extralumbar spinal sciatica. Female sex, right side involvement, and overlapping sensory disturbance are suggestive of extralumbar spinal sciatica associated with gynecologic conditions.

Mechanosensitive Afferent Units in the Lumbar Posterior Longitudinal Ligament

Study Design. The mechanosensitive afferent units in the lumbar posterior longitudinal ligament were investigated in an animal model using an electrophysiologic technique. Objectives. The objectives of this study were to identify the mechanosensitive receptive fields in the lumbar posterior longitudinal ligament and to investigate their distribution and characteristics. Summary of Background Data. The lumbar posterior longitudinal ligament has a nerve network originating from the sinuvertebral nerve. These fibers are thin, and most of their terminals are free nerve endings. Some immunohistochemical studies have indicated that they are immunoreactive to calcitonin gene-related peptide and/or substance P, suggesting a nociceptive function. Most of these studies investigated morphologic aspects, and there have been few studies employing electrophysiologic techniques to examine mechanosensitive units. Methods. We used 13 adult cats. They were anesthetized and then laminectomy was performed. The L5 and L6 dorsal rootlets were draped over a recording electrode. To investigate the receptive fields in the posterior longitudinal ligament, afferent impulses were evoked by mechanical stimulation with a glass probe. When the receptive fields were located, they were stimulated electrically to obtain conduction velocity and were stimulated with a set of 17 nylon filaments to determine their mechanical thresholds. Results. Thirteen units were identified in the lumbar posterior longitudinal ligament. The majority of the units were located around the intervertebral disc level of the posterior longitudinal ligament. The mean mechanical threshold was 47.04 ± 15.25 g. According to the conduction velocities of the units, 12 units were classified into Group III (0.5–2.5 m/sec) and one unit into Group IV (2.5–20 m/sec). Conclusion. Mechanosensitive units classified into Group III or Group IV and with a high mechanical threshold (>7.0 g) were thought to act as nociceptive units. All units identified in this study satisfied these criteria. Our result suggests that afferent fibers from the lumbar posterior longitudinal ligament have a principally nociceptive function.

Mechanosensitive afferent units in the shoulder and adjacent tissues.

Electrophysiologic experiments were done to identify the somatosensory afferent units in the shoulder and adjacent tissues of the rabbit. Conduction velocity and mechanical threshold of the units were examined to determine whether the units have a nociceptive function or proprioceptive function. Eighty mechanosensitive units were identified in the shoulder and adjacent tissues. Forty-six of these units were found in the rotator cuff area, 26 in the supraspinatus muscle, and eight in the infraspinatus muscle. These tissues contained low to high threshold Group II and Group III units. This study showed there are nociceptors that receive pain sensation and proprioceptors that receive position sense with motion of the shoulder in the rotator cuff and the supraspinatus and infraspinatus muscles. The high density of nociceptors found in the rotator cuff and infraspinatus muscles near their insertion to the shoulder suggests these tissues are more sensitive to noxious stimuli.