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Biomedical subjects

Koichi Iwata

Publications and source records attributed to Koichi Iwata.

At least 19 recordsLinked to original sources
PubMed2006

Recent advances in basic neurosciences and brain disease: from synapses to behavior.

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21-23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29-31, 2007).

Behavior↗
PubMed2006

Modulation of neuronal activity in CNS pain pathways following propofol administration in rats: Fos and EEG analysis.

We studied Fos expression in the central nociceptive pathways at different sedative levels in order to clarify the central mechanism of propofol's nociceptive action. Sprague-Dawley rats received propofol (PRO) or pentobarbital (PEN) and were divided into two groups with different doses of drug administration (light and deep sedative levels) based on the electroencephalogram analysis. Rats at each sedative level received heat stimulation to their face and Fos immunohistochemistry was performed at various brain sites. We also infused lidocaine into the jugular vein to test whether PRO directly activated nociceptors distributed in the vein. Fos expression in two major ascending pain pathways (lateral and medial systems) and descending modulatory system were precisely analyzed following intravenous (i.v.) administration of PRO or PEN. Many Fos protein-like immunoreactive (Fos protein-LI) cells were expressed in the trigeminal spinal nucleus caudalis (Vc), parabrachial nucleus, parafascicular nucleus, a wide area of the primary somatosensory cortex, anterior cingulate cortex, amygdala, periaqueductal gray, solitary tract nucleus, and lateral hypothalamus following heating of the face during PRO or PEN infusion. The number of Fos protein-LI cells was significantly greater in many Central nervous system regions during PRO infusion compared with PEN. Fos expression was significantly greater in the Vc and Periaqueductal gray following greater amount of PRO infusions compared, whereas they were significantly smaller in the Vc in the rats with PEN infusion. The Fos expression was significantly depressed following i.v. infusion of lidocaine before PRO administration. The present findings suggest that PRO is involved in the enhancement of Vc activity through direct activation of the primary afferent fibers innervating veins, resulting in pain induction during infusion.

Anesthesia↗
PubMed2006

Mechanisms involved in modulation of trigeminal primary afferent activity in rats with peripheral mononeuropathy.

In order to clarify the mechanisms underlying the changes in primary afferent neurons in trigeminal neuropathic pain, a chronic constriction nerve injury model of the infraorbital nerve (ION-CCI) was developed in rats. Mechanical allodynia was observed at 3 days after ION-CCI and lasted more than 14 days. Single-unit activities were recorded from the ION of anesthetized rats. C-, Abeta- and Adelta-units were identified on the basis of their conduction velocity. Adelta-units were frequently encountered at a later period after ION-CCI. The highest Adelta-spontaneous activity was recorded at 3 days after ION-CCI and progressively decreased after that, but spontaneous activity was still higher at 14 days after ION-CCI than that of naïve rats. Mechanical-evoked responses of Adelta-units were also highest at 3 days after ION-CCI and then gradually decreased. In consideration of these data, patch-clamp recordings were performed on medium to large size neurons of the dissociated trigeminal ganglion (TRG). Patch-clamp recordings revealed that the IK (sustained) and IA (transient) in rats with ION-CCI were significantly smaller than those of naïve rats, and correlated with an increase in duration of repolarization phase and a decrease in duration of depolarization phase, respectively. The hyperpolarization-activated current (Ih) was significantly larger in TRG neurons of rats with ION-CCI as compared with those of naïve rats. The present results suggest that Ih, IK and IA in Adelta-afferent neurons in TRG are significantly involved in the changes in afferent spontaneous activity and mechanically evoked activity that accompany mechanical allodynia produced by trigeminal nerve injury.

Action Potentials↗
PubMed2006

Differential responses of rostral subnucleus caudalis and upper cervical dorsal horn neurons to mechanical and chemical stimulation of the parotid gland in rats.

Blockage of the salivary duct can produce pain and inflammation from the build up of saliva in the parotid gland. The processing of parotid inflammation-induced pain, however, is poorly understood. The purpose of this study was to clarify the functional involvement of the trigeminal subnucleus interpolaris/caudalis transition region (Vi/Vc) and upper cervical spinal cord (C1/C2) in processing nociceptive input relevant to parotitis. The effect of capsaicin-induced parotitis was examined on a total of 37 nociceptive neurons isolated from the Vi/Vc (n = 23) and C1/C2 (n = 14) regions. Eight of 23 Vi/Vc neurons responded to mechanical distention of the parotid gland, whereas no C1/C2 neurons responded to the parotid distention. Receptive field characteristics in all neurons were examined following capsaicin injections into the parotid gland. Mechanical and cold responses increased significantly in C1/C2 but not Vi/Vc neurons following capsaicin. Receptive field sizes also increased in C1/C2 but not Vi/Vc neurons. At the Vi/Vc transition region, pinch-evoked activity increased in neurons receiving convergent inputs from the parotid gland and facial skin when compared to non-convergent neurons. The present data indicate that the hyperalgesia and referred pain associated with parotitis may result from sensitization of C1/C2, but not Vi/Vc nociceptive neurons.

Action Potentials↗
PubMed2006

Charge resonance character in the charge transfer state of bianthryls: effect of symmetry breaking on time-resolved near-IR absorption spectra.

We study the effects of symmetry breaking on the photogenerated intramolecular charge transfer (CT) state of 9,9'-bianthryl (BA) with femtosecond time-resolved near-IR spectroscopy. The time-resolved near-IR spectra are measured in acetonitrile for a symmetric substituted derivative of 10,10'-dicyano-9,9'-bianthryl (DCBA) and asymmetric substituted derivatives of 10-cyano-9,9'-bianthryl (CBA) and 9-(N-carbazolyl)anthracene (C9A), as well as nonsubstituted BA. The transient near-IR absorption spectrum of each compound at 0 ps has a locally excited (LE) absorption band, which agrees with the transient absorption band of the corresponding monomer unit. At 3 ps after the photoexcitation, the symmetric compounds show a broad charge transfer (CT) absorption band, whereas no absorption peak appears in the spectra of the asymmetric compounds. The broad CT absorption at 1250 nm only observed for the symmetric compounds can be attributed to the charge resonance transition associated with two equivalent charge separated states.

Journal Article↗
PubMed2006

Method for calibrating system parameters of a multidirectional interferometers system.

A multidirectional interferometer system has been proposed and developed to measure the position and orientation of a positioning stage. In this method the system parameters, such as positions of the corner-cube reflectors and directions of the rays in the interferometers, must be determined beforehand. However, it is difficult to find ways to determine the system parameters for each different system with necessary accuracy. This paper proposes a systematic method for calibrating the system parameters when the number of the interferometers is larger than the degrees of freedom of the stage. The method is verified for a two-dimensional stage by both simulation and experiment.

Journal Article↗
PubMed2006

Phosphorylation of Extracellular Signal-Regulated Kinase in medullary and upper cervical cord neurons following noxious tooth pulp stimulation.

The phosphorylated Extracellular Signal-regulated Kinase (pERK) and Fos expression and masticatory muscle activity were analyzed in rats with capsaicin-induced acute inflammation of the tooth pulp in order to clarify the role of the spinal trigeminal nucleus and upper cervical spinal cord in tooth pulp pain. Digastric and masseteric muscle activities were significantly increased following capsaicin injection into the molar tooth pulp but not after vehicle treatment. The pERK-like immunoreactive (LI) neurons were observed in the subnuclei interpolaris-caudalis transition (Vi/Vc) zone, the paratrigeminal nucleus (Pa5) and the superficial laminae of the caudal Vc/C2 zone. The pERK expression was detected as early as 2 min and peaked at 5 min after capsaicin or vehicle injection. The pERK expression in the Vi/Vc zone and Pa5 was bilateral, whereas it was predominantly ipsilateral in the caudal Vc/C2 zone. The capsaicin treatment of the whisker pad produced pERK expression in the rostro-caudal middle portion of the ipsilateral Vc, but small number of pERK-LI cells were observed after vehicle treatment. The pERK expression was similar in the Vi/Vc zone following capsaicin injection into the upper or lower molar tooth pulp, whereas the pERK expression was in the lateral portion of the caudal Vc/C2 zone after upper molar injection and restricted to the medial portion of the Vc/C2 zone after the lower molar capsaicin. These data were confirmed with Western blots. There were differences in the distribution of Fos protein-like immunoreactive (LI) cells and pERK-LI cells following tooth pulp stimulation. After capsaicin application into the upper molar tooth pulp, no pERK-LI cells were observed in the ventral part of the Vi/Vc zone, whereas many Fos protein-LI cells were expressed in this region. The difference in the distribution pattern of pERK- and Fos protein-LI cells in the Vi/Vc zone suggests their differential temporal expression profiles after capsaicin. The present findings suggest that tooth-pulp-driven neurons in the spinal trigeminal nucleus are involved in tooth pulp pain through activation of the intracellular signal transduction pathway that involves earlier ERK phosphorylation and subsequent Fos expression.

Animals↗
PubMed2006

Osteoclasts play a part in pain due to the inflammation adjacent to bone.

Bone disorders with increased osteoclastic bone resorption are frequently associated with bone pain and inhibitors of osteoclasts reduce bone pain. Osteoclasts degrade bone minerals by secreting protons through the vacuolar H+-ATPase, creating acidic microenvironments. Because acidosis is a well-known cause of pain, we reasoned that osteoclasts cause pain through proton secretion. We explored this using an animal model in which a single subcutaneous injection of the complete Freund's adjuvant (CFA) in the hind-paw caused inflammatory hyperalgesia (hyper-responsiveness to noxious stimuli). Osteoclastic bone resorption was increased in the metatarsal bones in the CFA-injected hind-paws. CFA-induced hyperalgesia was significantly suppressed by the bisphosphonates, zoledronic acid (ZOL) and alendronate and osteoprotegerin. c-src-deficient mice in which osteoclasts are inherently dysfunctional exhibited reduced CFA-induced hyperalgesia. Repeated subcutaneous injections of parathyroid hormone-related protein into the hind-paw also induced hyperalgesia with increased osteoclastic bone resorption. The hyperalgesia was associated with increased mRNA expression of acid-sensing ion channel (ASIC) 1a, 1b and 3 in the ipsi-lateral dorsal root ganglions (DRGs) by RT-PCR and c-Fos in the ipsi-lateral spinal dorsal horn by immunohistochemistry. Of note, ZOL decreased the ASIC1a mRNA expression and c-Fos. Treatment of the DRG cell line F-11 with acid (pH5.5) increased ASIC1a, 1b and 3 mRNA expression and nuclear c-Fos expression. The ASIC blocker amiloride inhibited acid-induced c-Fos expression in F-11 cells. Moreover, F-11 cells transfected with the transient receptor potential channel vanilloid subfamily member 1 (TRPV1) showed increased acid-induced nuclear c-Fos expression compared with parental F-11 cells. Finally, bafilomycin A1, an inhibitor of the vacuolar H+-ATPase, reversed the hyperalgesia and down-regulated ASIC1a mRNA expression in the DRGs. These results led us to propose that osteoclasts play a part in CFA-induced inflammatory pain through an activation of the acid-sensing receptors including ASICs and TRPV1 by creating acidosis.

Acid Sensing Ion Channels↗
PubMed2005

Anterior cingulate cortical neuronal activity during perception of noxious thermal stimuli in monkeys.

It has been reported that the anterior cingulate cortex (ACC) has a variety of functions relating to pain as well as pain perception. However, the underlying mechanisms for those functions remain unclear. To elucidate the functional role of the ACC in pain perception and pain-related functions such as attention to pain and escape from pain, single neuronal activity was recorded from the ACC, and the behavioral correlates of this neuronal activity was studied. A total of 667 neurons were recorded from the ACC in awake behaving monkeys. Twenty-one had modulated activity during a heat-detection task. Eighteen of these increased their firing frequency following an increase in stimulus temperature, whereas three of them had decreased firing during heating of the face. Seventy-five percent of heat-evoked responses of heat-responsive ACC neurons were significantly depressed when monkeys detected the change in magnitude of illumination of a light presented on the front panel. The neuronal activity was significantly higher when monkeys escaped from a noxious heat stimulus than when the monkeys detected a small change in temperature (T2) above a larger initial shift (T1). No relationship between firing frequency and detection latency of the T2 stimulation was observed. These findings suggest that ACC nociceptive neurons are involved in attention to pain and escape from pain but not in the sensory discriminative aspect of pain.

Action Potentials↗
PubMed2005

Effect of chronic inflammation on dorsal horn nociceptive neurons in aged rats.

To elucidate the effect of chronic inflammation on spinal nociceptive neurons in the elderly, we compared nocifensive behavior, peripheral inflammatory responses, and spinal dorsal horn neuronal activities between the aged (29-34 mo) and adult (7-12 mo) male rats after injection of complete Freund's adjuvant (CFA) into the hind paw. Aged rats exhibited a significantly lower mechanical paw withdrawal threshold before inflammation. However, after CFA injection mechanical allodynia developed in both adult and aged rats after CFA injection. The changes of foot temperature and thickness after CFA injection were greater and lasted longer in aged than in adult rats. Sets of 124 wide dynamic range (WDR) neurons (aged: 59, adult: 65) and 26 nociceptive specific (NS) neurons (aged: 13, adult: 13) were recorded from the lumber spinal dorsal horn. NS neurons from the inflamed adult rats showed significantly higher responses to noxious mechanical stimulation than those in aged rats, whereas WDR neurons from inflamed adult and aged rats were similar. Background activity of WDR neurons from the adult rats increased after CFA, whereas WDR neurons of aged rats and NS neurons from either group were not. The afterdischarge followed by noxious mechanical stimulation was significantly greater for WDR neurons in both adult and aged rats, whereas no significant differences were observed in NS neurons. Two days after CFA injection, Fos expression increased similarly in aged and adult rats. Thus the aged rats showed enhanced peripheral inflammatory responses to CFA injection with only a slight change in dorsal horn neuronal activity. Together with our previous finding that nociceptive neurons in aged rats exhibit hyperexcitability, these results suggest that the dorsal horn nociceptive system becomes sensitized with advancing age and its excitability cannot be further increased by inflammation.

Action Potentials↗
PubMed2005

Ca(2+)/calmodulin-protein kinase IIalpha in the trigeminal subnucleus caudalis contributes to neuropathic pain following inferior alveolar nerve transection.

Calcium-calmodulin protein kinase IIalpha (CaMKIIalpha) is mainly found in brain cells, and the mRNA concentrates highly in the postsynaptic density. CaMKIIalpha is an effector of calcium and calmodulin mediated functions, and the phosphorylated CaMKIIalpha (pCaMKIIalpha) activates glutamate receptors, such as the AMPA receptor, and enhances its function. In the present study, we examined whether CaMKIIalpha in trigeminal brainstem neurons contributed to the neuropathic pain induced by inferior alveolar nerve (IAN) transection. Using immunohistochemistry and in situ hybridization, we found that the expression of CaMKIIalpha and pCaMKIIalpha increased in the trigeminal subnucleus caudalis (Vc) after IAN transection. The significant increase in the protein of CaMKIIalpha peaked at 30 min after IAN transection, and the mRNA of CaMKIIalpha increased from 2 to 14 days. Double immunofluorescent staining for CaMKIIalpha and MAP2, a marker of dendrite, revealed a significant increase in the overlapping area at 30 min after injury. This suggests that CaMKIIalpha protein is synthesized from the local mRNA pool in the dendrite 30 min after IAN transection and may quickly transmit information after nerve injury. In the behavioral test in which the escape threshold from mechanical stimulation to the lateral face was measured, intrathecal administration of KN-93, a CaMKII inhibitor, for 7 days significantly inhibited mechano-allodynia induced by IAN transection, as compared with administration of a control peptide. These data suggest that CaMKIIalpha in the trigeminal subnucleus caudalis may be involved in neuropathic pain caused by IAN transection.

Animals↗
PubMed2005

Involvement of dorsal column nucleus neurons in nociceptive transmission in aged rats.

To clarify the functional role of the dorsal column nucleus (DCN) in nociception in rats with advancing age, single neuronal activity and substance P-like immunoreactivity (SP-LI) of the gracile nucleus (GN) were studied in aged rats (29 to 34 mo old) and adult rats (9 to 12 mo old). A total of 122 neurons [aged: 34 wide-dynamic-range (WDR), two nociceptive-specific (NS), and 32 low-threshold mechanical (LTM) neurons; adult: 22 WDR and 32 LTM neurons] were recorded from GN. For WDR neurons, the latency to antidromic activation of the ventral posterior lateral nucleus of the thalamus showed no difference between the aged and adult rats. Sciatic nerve stimulation with C-fiber intensity induced responses of GN with significantly longer latency in aged rats than in adults, whereas there was no difference in the response latency to A-fiber intensity stimulation. Background activity and afterdischarges were significantly higher in the aged rats than those in the adult rats. Responses to noxious mechanical and thermal stimuli were significantly greater in the aged rats during application of graded stimuli. There were no significant differences in responses to nonnoxious mechanical stimulus, mechanical response threshold, and the size of the receptive fields between neurons in the aged and adult rats. The area occupied by SP-LI fibers in the GN and the size of SP-LI dorsal root ganglia neurons were significantly larger in aged rats than in adults. The present findings suggest that the hyperexcitability of GN neurons could be involved in abnormal noxious pain sensations with advancing age.

Action Potentials↗
PubMed2005

Numerical study on an asymmetric guided-mode resonant grating with a Kerr medium for optical switching.

Optical switching effects of a guided-mode resonant grating (GMRG) with a Kerr medium have been simulated with the nonlinear finite differential time domain (FDTD) method. An asymmetric waveguide grating with a large second spatial harmonic component has been proposed for the optical switch. Resonant reflection occurs at both of the band-edge wavelengths. These wavelengths are used for the pump light and the probe light. The enhanced electric field of the pump light changes the resonant wavelength for the probe light as a result of the Kerr effect. We designed the GMRG with resonant wavelengths of 1489.6 and 1630 nm, which were used for the pump light and the probe light, respectively. When the grating material has a third-order susceptibility chi(3) of 8.5 x 10(-10) esu, the transmittance of the probe light changes from 0 to 80% by increasing the intensity of the pump light from 0 to 60 kW/mm2.

Journal Article↗
PubMed2005

Activation of trigeminal intranuclear pathway in rats with temporomandibular joint inflammation.

We examined the anatomical connections of trigeminal neurons between the trigeminal subnuclei interpolaris/caudalis (Vi/Vc) transition and caudal subnucleus caudalis/upper cervical dorsal horn (Vc/C(1,2)) zones in rats, using the fluorogold (FG) retrograde tracing method combined with Fos expression, a marker of neuronal activation, following temporomandibular joint (TMJ) inflammation. The head withdrawal threshold was also measured in rats 3 days after complete Freund's adjuvant (CFA)-induced TMJ inflammation. The head withdrawal threshold on the inflamed side was significantly decreased after CFA injection into the TMJ. FG was injected into the Vi/Vc transition zone and retrogradely labeled FG-positive cells were observed in the Vc/C(1,2) region. Numerous Fos protein-expressing cells were present both in the Vi/Vc transition zone and in the laminated Vc/C(1,2) zone. A population of cells was double-labeled with Fos and FG in the Vc/C(1,2) zone. Fos/FG cells were only observed in the deep laminae of the Vc/C(1,2) zone. These findings suggest that Vi/Vc transition zone activity is modulated by activation of the caudal laminated zone after orofacial tissue injury.

Analysis of Variance↗
PubMed2004

Activation of trigeminal nociceptive neurons by parotid PAR-2 activation in rats.

To clarify involvement of protease-activated receptor-2 (PAR-2) in parotid pain, we examined whether PAR-2 activation in the parotid gland could activate trigeminal nociceptive neurons in anesthetized rats, by analyzing immunoreactive Fos as a nociceptive marker. Either the PAR-2 agonist SLIGRL-NH2 or capsaicin, injected into the parotid duct, caused expression of Fos in the trigeminal subnucleus caudalis, although the PAR-2-inactive reversed peptide had no such effect. The Fos expression caused by PAR-2 activation was inhibited by ablation of capsaicin-sensitive sensory neurons. Intraductal SLIGRL-NH2 did not increase vascular permeability in the parotid gland. Our data thus reveal that activation of PAR-2 in the parotid gland can cause activation of trigeminal nociceptive neurons via capsaicin-sensitive sensory nerves most probably by a non-inflammatory mechanism.

Animals↗
PubMed2004

Alteration of the second branch of the trigeminal nerve activity following inferior alveolar nerve transection in rats.

After transection of the inferior alveolar nerve (IAN), the whisker pad area, which is innervated by the infraorbital nerve (ION) that was not injured, showed hypersensitivity to mechanical stimulation. Two days after IAN transection, threshold intensity for escape behavior to mechanical stimulation of the ipsilateral whisker pad area was less than 4.0 g, indicating mechanical allodynia. A total of 68 single fiber discharges were recorded from ION fibers at 3 days after IAN transection. The responses of C- and A-fibers were classified according to their conduction velocity. The C-fiber activities were not affected by IAN transection, whereas A-fiber activities were significantly enhanced by IAN transection as indicated by an increase in background activity and mechanically evoked response. Since the A-fiber responses were significantly affected by IAN transection, patch clamp recording was performed from middle to large diameter retrogradely labeled and acutely dissociated trigeminal ganglion (TRG) neurons. The I(K) (sustained) and I(A) (transient) currents were significantly smaller and hyperpolarization-activated current (I(h)) was significantly larger in TRG neurons of rats with IAN transection as compared to those of naive rats. Furthermore, current injection into TRG neurons induced high frequency spike discharges in rats with IAN transection. These data suggest that changes in K(+) current and I(h) observed in the uninjured TRG neurons reflect an increase in excitability of TRG neurons innervated by the ION after IAN transection, resulting in the development of mechano-allodynia in the area adjacent to the injured IAN innervated region.

Action Potentials↗
PubMed2004

Trigeminal neuronal recording in animal models of orofacial pain.

The electrical signal associated with nerve cells, mainly as a result of changes in the membrane potential during functional activity, can be recorded extracellularly to study central mechanisms underlying sensory processing. The secondary neurons in the spinal trigeminal complex receive inputs from peripheral neurons that innervate the orofacial region and forward information to the higher levels of the nervous system. Analyzing activity patterns of trigeminal neurons related to pain perception has proven to be an efficient method in studying orofacial pain mechanisms. Here we describe some basic techniques and tips for extracellular single neuron recording from the subnucleus caudalis of the trigeminal spinal nucleus in rats with orofacial injury. Two different rat models with temporomandibular joint inflammation and inferior alveolar nerve transection are described.

Action Potentials↗