Hozumi Tatsuoka

Change of dorsal horn neurochemistry in a mouse model of neuropathic cancer pain

&NA; We investigated some neurochemical changes that take place in the spinal cord dorsal horn in a mouse model of neuropathic cancer pain. The model was produced by inoculation of Meth‐A sarcoma cells to the vicinity of the sciatic nerve, which resulted in growth of a tumor mass embedding the nerve. Hind paw‐lifting, a behavioral sign of spontaneous pain, was at maximum on Day 18, but decreased thereafter. The decrease was likely caused by progression of motor paralysis. On Day 18, thermal and mechanical pain thresholds of the affected paw were significantly increased. Histologically, the sciatic nerve presented damages to both unmyelinated and myelinated fibers on Day 18, which were more pronounced on Day 25. In the spinal cord, c‐Fos‐positive cells were significantly increased in the superficial and deep layers on Day 18. The number of c‐Fos‐positive cells in the superficial layer correlated with the duration of paw‐lifting. The increase in c‐Fos‐positive cells was still present on Day 25 despite decreased paw‐lifting. Substance P and calcitonin gene‐related peptide were up‐regulated on Day 18 but down‐regulated on Day 25. A marked up‐regulation of dynorphin A (DynA) was present on Day 18 and persisted through Day 25. Our model caused progressive damage to the sciatic nerve and presented spontaneous pain‐behavior while the paw became hyposensitive to mechanical and thermal stimuli. Since the up‐regulation of DynA in the dorsal horn persisted and paralleled the increase in c‐Fos‐positive cells, the release of DynA may be associated with spontaneous pain in our model.

Behavioral and morphologic studies of the chronically compressed cauda equina. Experimental model of lumbar spinal stenosis in the rat.

STUDY DESIGN An experimental model in rats of chronically compressed cauda equina was produced, and behavioral and morphologic changes were examined. OBJECTIVES To provide a useful model for analyzing the pathophysiologic changes of the cauda equina by chronic compression and to examine behavioral and morphologic changes in this model. SUMMARY OF BACKGROUND DATA Several animal models have been reported in which various materials were used to compress the cauda equina. However, the pathophysiology of the cauda equina by chronic compression is not yet well understood. Studies in which rats were used are scarce. METHODS A silicone sheet was applied to the spinal canal at L4 in the rat. Walking durations on treadmill tests and paw-withdrawal latencies to thermal stimuli were measured before and after the operation for 24 weeks. Histologic changes also were examined. RESULTS Walking durations decreased after chronic compression. However, paw-withdrawal latencies were not significantly changed. Histologically, the number of large-diameter myelinated axons decreased after compression, whereas the number of small-diameter myelinated axons increased. Electron microscopic observation indicated that the continuous degeneration and regeneration of axons occurred throughout the chronic compression experiment. CONCLUSIONS The current model and behavioral assessments may be useful in analyzing the pathophysiology of chronically compressed cauda equina.

The effects of moderate-intensity gradient static magnetic fields on nerve conduction

Whether exposure to static magnetic fields (SMF) for medical applications poses a therapeutic benefit or a health hazard is at the focus of current debate. As a peripheral nerve model for studies of the SMF effects, we have investigated whether exposure of in vitro frog sciatic nerve fibers to moderate-intensity gradient SMF up to 0.7 T modulates membrane excitation and refractory processes. We measured the changes in the amplitudes of the electrically evoked compound action potentials for three groups: a control group without SMF exposure and two exposed groups with continuous inhomogeneous exposure to maximum flux densities (B(max)) of 0.21 and 0.7 T SMF for 6 h. The values of the nerve conduction velocity of C fibers were significantly reduced by B(max) of 0.7 T SMF during the 4- to 6-h exposure period but not by B(max) of 0.21 T SMF during the entire exposure period of 6 h, relative to the unexposed control. From these findings, we speculate that exposure to moderate-intensity gradient SMF may attenuate pain perception because the C fibers are responsible for pain transmission. Although the mechanistic reasons for this decrease have yet to be clarified, SMF could affect the behavior of some types of ion channels associated with C fibers.

The morphological differences of stereocilia and cuticular plates between type-I and type-II hair cells of human vestibular sensory epithelia.

The sensory epithelia of macula utriculi were examined by conventional and intermediate voltage transmission electron microscopy. The specimens were obtained from three cases of acoustic neurinoma who were operated on using the translabyrinthine approach. The mean diameter of the vestibular hair cell stereocilia was obtained and the cuticular plates of type-I and type-II hair cells were reconstructed three-dimensionally from the consecutive 0.5-micron-thick sections. The mean diameter of stereocilia of type-I hair cells was 488 +/- 59 nm (n = 13) and that of stereocilia of type-II hair cells was 373 +/- 21 nm (n = 14). Stereocilia of type-I hair cells numbered about 70 and those of type-II hair cells about 50. The cuticular plates of type-I hair cells were several times as thick as those of type-II hair cells. The cuticular plate of the type-I hair cell appeared to be an inverse cone and that of the type-II hair cell seemed to be a flat disc.

Vestibular sensory epithelia in patients with acoustic neurinoma

The human vestibular sensory epithelia of the macula utriculi were examined ultrastructurally in 13 cases with acoustic neurinoma. The sensory epithelia were fairly well preserved, with several morphological changes such as lipofuscin granules, intraepithelial cysts, pyknosis, vacuoles, laminated structures, banded structures and degeneration of subepithelial myelinated nerves evident. The pathological significance of these findings was discussed. There were thickened irregular membrane formations in spaces between the nerve calyces and type I hair cells which might be related to acoustic neurinoma. Some type I hair cells were incompletely surrounded by nerve calyces. The neck regions of these cells received direct contact from the efferent nerve endings.

Effect of 1.5 T steady magnetic field on neuroconduction of a bullfrog sciatic nerve in a partially active state within several hours after extraction.

The bullfrog sciatic nerve within six hours after extraction was determined from the change with time in the action potential and the impedance to be a partially active nerve. Steady magnetic fields have been determined to be ineffective in the neuroconduction in the fresh nerve just after extraction. Although ion motions involved in the neuroconduction in the partially active nerve are not normal, it was confirmed that a 1.5 T steady magnetic field is ineffective in the neuroconduction in the partially active nerve. The obtained results suggest that the neuroconduction in damaged nerves is not affected by the 1.5 T steady magnetic field used in MRI.

Nerve excitation and recovery processes under strong static magnetic fields

The membrane excitation and refractory processes of nerve fibers exposed to strong static magnetic fields of 8 T were studied. Sciatic nerve bundles of frogs were electrically excited by a pair of pulses with varying interpulse intervals, and the compound action potentials were measured under magnetic field exposures. Our experimental results show that the conduction velocity was not affected by 8 T magnetic fields; however, the membrane excitation during the recovery process in the relative refractory period was enhanced by 10% of maximal peak of nerve excitation by magnetic field exposure for 3 h. In this study, the optimal time interval for increased membrane excitation during the recovery process was between 1.0 and 1.1 ms. In other words, membrane excitation during the recovery process in the relative refractory period was affected by the magnetic fields just after Na+ channels were inactivated.

Distribution of vasoactive intestinal polypeptide immunoreactive nerve fiber in the rat nasal mucosa

The distribution of vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fiber of the respiratory nasal mucosa of the rat was examined by use of immunohistochemistory with light, laser confocal scanning and electron microscopy. On light microscopy, it was observed that VIP immunoreactive nerve fibers distributed under and within the epithelium in addition to around the blood vessels and glands. The laser confocal scanning microscope revealed the network of VIP-immunoreactive nerve fibers at glands, but it was denser around glands than within glands. The VIP-immunoreactive nerve fibers formed fine varicosities and was distributed below the middle portion of the epithelium. Some fibers were observed as if they were surrounding goblet cells. Electron microscopy showed that the VIP-immunoreactive nerve fibers within the epithelium were terminated as free nerve endings. Some of them were in close contact with goblet cells.

Atypical Innervation Pattern of Human Vestibular Hair Cells

Human vestibular sensory epithelia of macula utriculi were examined in 3 cases with acoustic neurinoma by intermediate voltage electron microscope. The innervation pattern of vestibular hair cells was studied by means of computer aided three-dimensional reconstruction technique. The sensory epithelia were fairly well preserved. Most of type I and all of type II hair cells appeared normal. However, some type I hair cells were incompletely surrounded by nerve calyces and received direct contact from the efferent nerve endings. These type I hair cells were also innervated by a few neighboring afferent nerve calyces. These atypical type I hair cells constituted 5-8% of the total number of hair cells.

Freeze-fracture study of the lateral-line canal organ of the Japanese sea eel, Lincozymba nystromi

SummarySpecializations of apical surfaces of hair cells, supporting cells and marginal cells in the lateral-line canal organ of Japanese sea eel, Lincozymba nystromi, were examined with a freeze-fracture technique. Apical surfaces of hair cells have a lower density of intramembrane particles (IMP) than those of the surrounding supporting cells. Density of IMP on the streocilia is almost the same as that on the apical surface of hair cells. Junctions between hair and supporting cells were tighter than those between two supporting cells; those between supporting and marginal cells were tighter than those between hair and supporting cells, and those between two marginal cells were the tightest in the lateral-line canal organ.