Biomedical subjects

Koichi Iwata

Publications and source records attributed to Koichi Iwata.

29 records · Page 2Linked to original sources

PubMed2004

Central neuronal changes after nerve injury: neuroplastic influences of injury and aging.

Peripheral nerve injury produces a hyperexcitability of primary afferents and neurons in the spinal cord that is considered important in the development of nerve injury-induced pain. The authors recently developed a nerve injury model in the trigeminal region of the rat to study the neuronal mechanism of neuropathic pain in the trigeminal system. The escape thresholds to mechanical stimulation applied to the whisker pad area were significantly lower in rats with an inferior alveolar nerve (IAN) transection than those evoked from the contralateral, sham-operated whisker pad. Also, background activity and mechanically evoked responses in infraorbital nerve (ION) afferents and hyperpolarization-activated current (Ih) in trigeminal ganglion ION neurons were increased following IAN transection. Background activity and mechanically evoked responses of wide dynamic range (WDR) neurons in trigeminal subnucleus caudalis on the ipsilateral side relative to the transection were also significantly increased after the operation. A large number of cells expressed c-Fos-like immunoreactivity in the caudal medulla and upper cervical spinal cord following non-noxious mechanical stimulation of the faces of rats with IAN transection. The effect of aging on spinal dorsal horn neurons and the involvement of nerve injury in producing abnormal pain sensation in rats with advancing age were also studied. The incidence of licking behavior in response to noxious radiant heat stimulation of the hind paw was lower in the aged rats than in younger adults, but paw withdrawal latency was shorter and the activities of spinal dorsal horn neurons were higher in the aged rats. Furthermore, the descending inhibitory systems were impaired in the aged rats. These observations suggest that the changes in neuronal activity in the aged rats likely corresponded to the changes observed in the rat model of peripheral nerve injury.

Aging↗

PubMed2003

Measurement of profiles along a circle on two flat surfaces by use of a Fizeau interferometer with no standard.

A method for measuring profiles along a circle on a flat surface with no standard is described. For the measurement, two unknown surfaces are placed almost parallel, and the distance between them is measured many times along a circle by rotation of one of the surfaces. Profiles of the two surfaces can be determined from the distance data. In this study the measuring method is explained: The space between two surfaces measured with a Fizeau interferometer. Four measuring experiments are carried out for determining the profile of a precision-grade half-mirror; in each experiment a different ordinary mirror with unknown profile is used as the second mirror. Profiles of the precise mirrors obtained by these experiments agree closely, with deviations of approximately 2 nm. A similar experiment with many concentric circles was carried out with a precise half-mirror and another precise mirror. Although the profiles of many concentric circles were independent of one another, the result shows that the high-frequency component of a whole plane can be estimated.

Journal Article↗

PubMed2003

Measurement by multidirectional interferometers of the position and orientation of a positioning stage.

A multidirectional interferometer system is developed to determine the position and orientation of a stage moved in a two-dimensional (2-D) space. In this system four corner-cube prisms are mounted on the moving stage, and four laser beams are incident on the corner cubes in different directions. Moving distances in the observed directions are measured by laser interferometers. The position and orientation of the stage are calculated from the moving distances of the corner cubes. Some experiments are done on the 2-D moving stage with four interferometers, and measurement errors are estimated from redundant data. The estimated accuracy is higher than 0.2 microm for translation and 0.3 x 10(-3) deg for rotation for a measurement range of 0.5 mm and 0.5 deg.

Journal Article↗

PubMed2002

Influence of oro-facial sensory input on the output of the cortical masticatory area in the anesthetized rabbit.

In order to study the role of sensory inputs to the cortical masticatory area (CMA) and plasticity in the CMA, the representation of sensory inputs and the change of sensory inputs and motor outputs in the CMA 16 days after trigeminal deafferentation in the rabbit were examined. Neuronal activity was recorded in response to mechanical and electrical stimulation of the oro-facial region and cortically-induced rhythmical jaw movements (CIRJMs) were analyzed. Cortical neurons with receptive fields in the deafferented region were not found in the CMA. However, the projection area of the intact lingual nerve extended both antero-posteriorly and medio-laterally in the CMA and included neurons with long latency responses to lingual nerve stimulation. In a previous study in the rabbit, CIRJMs were classified into two groups according to their similarity to normal masticatory patterns: one pattern resembled that occurring during the food transport stage (T-pattern), and the other resembled that occurring during the chewing stage (C-pattern). These two patterns of CIRJMs were evoked from different stimulation sites: T-patterns were induced from the dorsal CMA and C-patterns were induced from the ventral CMA. The relationship between the patterns of CIRJMs and the site of stimulation in the deafferented rabbits was similar to that observed in normal rabbits. This finding suggests that sensory inputs to the CMA may not directly influence the CMA motor outputs controlling jaw movements, despite a close spatial relationship between the input and output of this area.

Animals↗

PubMed2002

Phosphorylation of extracellular signal-regulated kinase in primary afferent neurons by noxious stimuli and its involvement in peripheral sensitization.

Alteration in the intracellular signal transduction pathway in primary afferent neurons may contribute to pain hypersensitivity. We demonstrated that very rapid phosphorylation of extracellular signal-regulated protein kinases (pERK) occurred in DRG neurons that were taking part in the transmission of various noxious signals. The electrical stimulation of Adelta fibers induced pERK primarily in neurons with myelinated fibers. c-Fiber activation by capsaicin injection induced pERK in small neurons with unmyelinated fibers containing vanilloid receptor-1 (VR-1), suggesting that pERK labeling in DRG neurons is modality specific. Electrical stimulation at the c-fiber level with different intensities and frequencies revealed that phosphorylation of ERK is dependent on the frequency. We examined the pERK in the DRG after application of natural noxious stimuli and found a stimulus intensity-dependent increase in labeled cell size and in the number of activated neurons in the c- and Adelta-fiber population. Immunohistochemical double labeling with phosphorylated ERK/VR-1 and pharmacological study demonstrated that noxious heat stimulation induced pERK in primary afferents in a VR-1-dependent manner. Capsaicin injection into the skin also increased pERK labeling significantly in peripheral fibers and terminals in the skin, which was prevented by a mitogen-activated protein kinase/ERK kinase inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminopheylthio)butadiene (U0126). Behavioral experiments showed that U0126 dose-dependently attenuated thermal hyperalgesia after capsaicin injection and suggested that the activation of ERK pathways in primary afferent neurons is involved in the sensitization of primary afferent neurons. Thus, pERK in primary afferents by noxious stimulation in vivo showed distinct characteristics of expression and may be correlated with the functional activity of primary afferent neurons.

Action Potentials↗

PubMed2002

Involvement of glutamate receptors on hyperexcitability of wide dynamic range neurons in the gracile nucleus of the rats with experimental mononeuropathy.

In order to clarify the functional role of glutamate receptors of the gracile nucleus neurons in rats with nerve injury-induced hyperalgesia, pharmacological, electrophysiological and in situ hybridization techniques were used in rats with chronic constriction nerve injury (CCI) of the sciatic nerve. A total of 54 wide dynamic range neurons were recorded from the gracile nucleus in the rats with CCI. Mechanical evoked responses were significantly depressed following application of AMPA receptor antagonist, CNQX, with noxious and non-noxious responses being similarly affected. AP-5, an NMDA receptor antagonist, induced depression of the pressure-evoked response only after application of the 1-microM concentration of this drug. The size of the receptive fields was significantly decreased after CNQX, but not MK-801 or AP-5, application. Afterdischarge was significantly depressed following the application of CNQX (1000 microM). The expression of ionotropic glutamate receptor subunit mRNAs in the gracile nucleus was studied using the in situ hybridization technique. The signals for NMDA subunits, NR2A, -2B and -2C, in the gracile nucleus neurons were not prominent, suggesting a low level expression of functional NMDA receptor complex. AMPA receptor subunits GluR1, -R2, -R3 and -R4 mRNAs were expressed in a large number of gracile nucleus neurons. These data are consistent with the pharmacological results that AMPA receptor antagonists depressed nociceptive neuronal activity, but NMDA receptor antagonists showed limited effects. These results suggest that the ionotropic glutamate receptors, i.e. the AMPA and NMDA receptors, are differentially involved in modulation of the wide dynamic range neuronal activity in the gracile nucleus following peripheral nerve injury.

Animals↗

PubMed2002

Induction of Fos protein-like immunoreactivity in the trigeminal spinal nucleus caudalis and upper cervical cord following noxious and non-noxious mechanical stimulation of the whisker pad of the rat with an inferior alveolar nerve transection.

After transection of the inferior alveolar nerve (IAN: the third branch of the trigeminal nerve), the whisker pad area, which is innervated by the second branch of the trigeminal nerve, showed hypersensitivity to mechanical stimulation. Two days after IAN transection, the threshold intensity for escape behavior to mechanical stimulation of the ipsilateral whisker pad area was less than 1.0 g, a sign of allodynia, and returned to the preoperative level (preoperative threshold: 52.0 g) at 32 days after surgery. This decrement of escape threshold lasted for more than 3 weeks. The whisker pad area contralateral to the IAN transection also showed a decrease in escape threshold to non-noxious mechanical stimulation as compared with sham-operated rats. However, the change in threshold intensity for the side contralateral to transection was not as pronounced as that on the ipsilateral side. Fos protein-like immunoreactive (LI) cells were observed in the superficial laminae but not dominant in deeper laminae of the trigeminal spinal nucleus caudalis (Vc) and the first segment of the spinal cord (C1) after non-noxious mechanical stimulation of the whisker pad area in the rats with IAN transection. Fos protein-LI cells were expressed bilaterally in the Vc and C1, but were more numerous on the ipsilateral side to transection than on the contralateral side. The largest number of Fos protein-LI cells was observed at 2400 microm caudal from the trigeminal subnucleus interporalis (Vi)-Vc border both in ipsilateral and contralateral sides. The number of Fos protein-LI cells increased after application of 1, 4, and 16 g stimuli as compared to rats without mechanical stimulation. Furthermore, an extensively greater number of Fos protein-LI cells were expressed both in superficial and deep laminae of the bilateral Vc and C1 of the spinal cord after subcutaneous injection of mustard oil into the whisker pad. Fos protein expression after mustard oil injection was much stronger than that observed after any mechanical stimulation in the rats with IAN transection. These data suggest that the change in the numbers and spatial arrangement of nociceptive neurons in the Vc and C1 after IAN transection reflect the development of mechanical hyperalgesia in the area adjacent to the IAN innervated region.

Animals↗

PubMed2002

Plastic changes in nociceptive transmission of the rat spinal cord with advancing age.

To understand characteristics of the pain system in the elderly, we investigated the electrophysiological properties of nociceptive neurons in the lumbar spinal dorsal horn of aged (29-34-mo old) and adult (7-13-mo old) rats. The responses of nociceptive neurons to noxious thermal stimulation, as well as the spontaneous firing rate, were significantly higher in the aged as compared with adult rats. Furthermore, the size of the high-threshold receptive field area of wide dynamic range neurons was larger (P < 0.01) and that of the low-threshold area was smaller (P < 0.05) in aged rats than in adult rats. The increased nociceptive neuronal activity in the aged rats correlated with the finding that the paw withdrawal latency was significantly shorter in the aged rats than those of the adult rats following heat stimulation of the hind paw (P < 0.05). Reversible local anesthetic block of descending pathways resulted in a dramatic increase in neuronal activity in adult rats but had little effect in aged rats. There was also a significant loss of serotoninergic and noradrenergic fibers in the spinal dorsal horn of the aged rats. These results demonstrate an age-related plasticity in spinal nociceptive processing that is related to impairment of descending modulatory pathways.

Aging↗

PubMed2002

Guided-mode resonant grating filter with an antireflection structured surface.

We describe a new structure of guided-mode resonant grating (GMRG) filters with low sideband reflectance. This GMRG filter consists of a high-index thin film on an antireflective structured surface called "moth-eye structure." Since the high-index film undulates along the surface structure, the film acts as a modulated optical waveguide. An incident light wave satisfying a resonant condition is reflected by the GMRG filter, and nonresonant light waves pass through the filter. This GMRG filter is valid for reducing reflection of nonresonant light waves in a wide spectral range. The resonant reflection of this new filter was investigated by numerical calculation based on an electromagnetic grating analysis. In the case of a triangular antireflective surface structure whose thickness is 2x greater than its period, the sideband reflectance for nonresonant light waves was lower than 0.5% for TM-polarized light in a wide range of wavelengths.

Journal Article↗

PubMed2001

A selective increase in Fos expression in spinal dorsal horn neurons following graded thermal stimulation in rats with experimental mononeuropathy.

In order to clarify the central mechanisms of thermal hyperalgesia produced by peripheral nerve injury, Fos protein-like immunoreactive (Fos-LI) cells in spinal dorsal horn neurons were studied in rats with chronic constriction nerve injury (CCI) following graded thermal stimulation of the hind paw. The graded thermal stimuli (cold: 5, 10 and 15 degrees C, heat: 42, 46 and 54 degrees C) were applied to the plantar surface of the operated hind paw 14 days after CCI or sham operation, and the number of Fos-LI cells in the spinal dorsal horn was quantified. Many Fos-LI cells were expressed in the superficial laminae of the spinal dorsal horn both in sham-operated and CCI rats following thermal stimulation. Fos-LI cells were mainly restricted to the medial half of the superficial laminae of the spinal dorsal horn, and were sparsely distributed in the deeper laminae. The number of Fos-LI cells in the superficial laminae (laminae I--II) of the dorsal horn was significantly higher in CCI rats after stimulation at 10 and 46 degrees C, but not at the other stimulating temperatures (5, 15, 42, and 54 degrees C) as compared to that in sham-operated rats. In laminae III-IV, the number of Fos-LI cells was significantly higher at all stimulus temperatures in CCI rats when compared to the sham-operated rats. No distribution difference of Fos-LI cells was observed between CCI and sham-operated rats in laminae V--VI. Thus, in the spinal dorsal horn of the CCI rats, there was a selective increase in thermal stimulus-induced Fos-LI cells in the superficial dorsal horn after stimulating at near noxious threshold intensities and a non-selective increase in Fos-LI cells in laminae III--IV after both noxious and innocuous thermal stimuli. The increase of Fos-LI cells in the superficial laminae may be related to hypersensitivity to noxious stimuli while the increase of Fos-LI cells in laminae III--IV may be related to an increased sensitivity to both noxious and innocuous stimuli that leads to increased reflex activity following nerve injury.

Animals↗

PubMed1998

Responses of dorsal column nuclei neurons in rats with experimental mononeuropathy.

To examine the functional role of dorsal column nuclei in neuropathic pain, electrophysiological properties of low- and high-threshold dorsal column nuclei neurons in neuropathic and normal rats were examined. Single-neuronal activities were recorded from the gracile nucleus (GN) in rats at 10-14 days after application of four loose ligatures around the sciatic nerve (chronic constriction nerve injury; CCI). A total of 190 units were recorded from the GN in naive and CCI rats. The largest population of low-threshold mechanoreceptive (LTM) neurons recorded from the GN of naive rats were classified as rapidly-adapting (RA) LTM neurons, whereas those from CCI rats were slowly-adapting (SA) neurons. Mean orthodromic latencies of GN neurons ipsilateral to the CCI after sciatic nerve stimulation were significantly longer than those of naive animals and those of GN neurons without receptive fields were significantly longer than any other type of neurons. One hundred and eight of 190 GN neurons were also antidromically activated following electrical stimulation of the ventro-lateral posterior nucleus of the thalamus. Furthermore, when stronger stimuli were applied to the sciatic nerve, some GN neurons also responded with long latencies. GN neurons of sham-operated naive rats and those contralateral to the CCI had mechanical receptive fields on the paw, whereas 8.0% of the GN neurons in the CCI side did not have any detectable mechanical receptive field. Receptive field size was not significantly different between neurons ipsilateral or contralateral to the CCI and those of naive rats. Spontaneous activity of GN neurons from the ipsilateral side was significantly higher than those from the contralateral side. On the other hand, spontaneous activity of GN neurons both ipsilateral and contralateral to the CCI were significantly higher than those from naive rats. Furthermore, afterdischarges of GN neurons ipsilateral and contralateral to the CCI were significantly higher than those of naive rats. The present data suggest that the dorsal column pathway is involved in CCI-produced sensory abnormalities by conveying their hyperactivity to thalamic neurons.

Animals↗