Natsu Koyama

Shiga University of Medical Science, Ōtu, Shiga, Japan

Are you Natsu Koyama?

Claim your profile

Publications (31)76.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Intradermal injection of an active compound of European honeybee toxin, melittin, into the forearm in humans produces temporary pain and evokes sustained increase of local skin temperature. This increase of skin temperature is suppressed by the pretreatment of a voltage gated sodium channel blocker, lidocaine, suggesting that neurogenic inflammation is involved in the skin temperature increase after the melittin treatment. In this study, we tested a hypothesis that the melittin-induced skin temperature increase is augmented by an N-methyl-D-aspartate (NMDA) glutamate receptor that is present on the peripheral terminals of cutaneous primary afferents. Skin temperature was examined after the local application of incremental doses of melittin by a computer-assisted-thermography in pentobarbital-anesthetized rats. Local subcutaneous glutamate was collected through a microdialysis probe and glutamate levels were measured by a high pressure liquid chromatography with electrochemical detection method. Intraplantar injection of melittin resulted in the increase of subcutaneous glutamate levels and the increase of local skin temperature, which was partially attenuated by co-injection of an NMDA receptor antagonist, MK-801. In addition, intraplantar injection of NMDA itself increased the local skin temperature. Our data suggest that melittin-induced increase of skin temperature is enhanced through the activation of peripheral NMDA receptors by locally released glutamate. We suggest that topical administration of NMDA receptor antagonists could be an effective treatment of neuro-inflammatory pain.
    Neurochemical Research 08/2012; 37(10):2222-8. · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Melittin is the main toxin of honeybee venom. Previously, we have reported that intradermal injection of melittin into the volar aspect of forearm in humans produces a temporary pain and a subsequent sustained increase in the skin temperature due to axon reflex. To clarify the interaction between nociceptive inputs and vascular changes, we studied the influence of noxious stimulation by intradermal melittin on the vasomotor control of the distal extremities in human volunteers. Temperature changes of the bilateral palmar surface were recorded by means of a computer-assisted infrared thermography. Unexpectedly, we found a biphasic response of skin temperature. The skin temperature of both fingers and hands decreased immediately after the melittin injection and then increased well above the control level, prior to the injection. There was a considerable individual variation in the baseline skin temperature, prior to melittin. The skin temperature in a finger/hand with lower preinjection value increased more markedly in the second phase. Consequently, the individual variation in the peak temperature of the second phase was less pronounced. The initial decrease was interpreted as sympathetic vasoconstrictor reflex induced by noxious stimulation and the later increase as release of sympathetic vasomotor tone.
    European Journal of Pain 02/2002; 6(6):447-53. · 3.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We assessed the effects of oxcarbazepine, an antiepileptic derivative of carbamazepine, on discharges in single cutaneous afferent fibers produced by repetitive high-frequency stimulation (mimicking the abnormal excitation of peripheral nerves in neuropathic pain and paresthesia). After intravenous administration of oxcarbazepine, the later responses in the train dropped out without the earlier ones being affected and, thus, the total number of spikes decreased. The latency of the responses to an individual pulse was unchanged. These results, which indicate that oxcarbazepine inhibits the generation of high-frequency firing without affecting impulse conduction, suggest that this drug may be useful against neuropathic pain and paresthesia.
    European Journal of Pharmacology 06/2001; 420(2-3):119-22. · 2.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intravenous picrotoxin inhibits spinal nociceptive neurons through disinhibitory activation of neurons in the periaqueductal gray (PAG) and nucleus raphe dorsalis (NRD), where the descending antinociceptive system arises. We found Fos-like immunoreactivity in PAG/NRD neurons after intravenous injection of picrotoxin. This distribution of c-Fos expression is consistent with a role of PAG/NRD for antinociception; neurons with intense Fos-like immunoreactivity was also clustered in the Edinger-Westphal nucleus (EW). Double fluorescence immunohistochemistry for c-Fos and serotonin revealed that PAG/NRD/EW neurons expressing c-Fos were non-serotonergic. These data suggest that non-serotonergic PAG/NRD/EW neurons are involved in the picrotoxin-induced analgesia.
    Neuroscience Letters 10/2000; 291(3):147-50. · 2.03 Impact Factor
  • Source
    N Koyama, K Hirata, K Hori, K Dan, T Yokota
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to investigate whether melittin, the principal toxin of the honeybee (Apis mellifera) venom, can be used as an algogenic agent in the study of pain in humans. Five micrograms of melittin in 0.5 ml of saline was intradermally injected into the volar aspect of the forearm. Resultant pain was scored by a visual analogue scale (VAS), and skin temperature change was analyzed by means of a computer-assisted infrared thermography. Intradermal melittin temporarily produced severe pain, followed by a sustained increase in skin temperature. The skin temperature increase peaked in about 10 min and outlasted 1 h. Topical application of 10% lidocaine gel did not significantly suppress the melittin-induced pain, but markedly suppressed both the increase in the peak temperature and the area of temperature increase. In conclusion, 5 microg of melittin is sufficient to produce pain in humans and 10% lidocaine gel differentially decreases the melittin-induced axon reflex without any significant analgesic effect.
    Pain 03/2000; 84(2-3):133-9. · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thalamic nociceptive neurons receiving afferent input from the tooth pulp (TP) were recorded from the nucleus ventralis posteromedialis proper (VPM) in cats anesthetized with urethane and chloralose. Effects of cervical vagus nerve stimulation on responses of TP neurons in the VPM were investigated. Twenty-one tooth pulp specific (TPS) and eight wide dynamic range (WDR) neurons with TP input were obtained from the periphery (shell region) of the posterior half of the VPM. Of these, many were also excited by electrical stimulation of trigeminothalamic tract (TTT) fibers in the trigeminal medial lemniscus. A conditioning-test paradigm was used to examine effects of vagal stimulation on responses of VPM neurons to electrical stimulation of TP and TTT. Inhibition of the responses was observed in 12 TPS and seven WDR neurons. Local anesthetic block of the mesencephalic periaqueductal gray (PAG) and/or nucleus raphe dorsalis (NRD) eliminated the inhibitory effects of vagal stimulation on the responses of both classes of TP neurons to TTT stimulation. In contrast, the inhibitory effects on responses to TP stimulation were insignificantly affected. These data suggest that vagal afferents can activate the ascending antinociceptive pathway from PAG/NRD onto VPM, in addition to activating the descending antinociceptive system acting upon the lower brain stem.
    Brain Research 07/1999; 833(1):108-11. · 2.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Effects of intravenous administration of picrotoxin (PTX), a GABA(A) receptor antagonist, upon activities of wide dynamic range (WDR) neurons in the lumbar spinal cord were studied in urethane-chloralose anesthetized cats. Intravenous PTX augmented tactile evoked responses of WDR neurons, but reduced nociceptive responses dose-dependently. Spinal transection reversed the suppression of nociceptive responses. In the spinal cat, intravenous PTX enhanced the tactile evoked response. Intravenous PTX enhanced the spontaneous firing of nucleus raphe dorsalis (NRD) and/or ventral periaqueductal gray (PAG) neurons projecting to nucleus raphe magnus. Lidocaine injected into NRD/PAG reversed the antinociceptive action of intravenous PTX. PTX injected into NRD/PAG reduced heat-evoked responses of WDR units. These data suggest that antinociceptive effects of intravenous PTX is primarily due to disinhibitory activation of the descending antinociceptive system originating from NRD and PAG, and that PTX reinforces touch-evoked responses in the spinal cord.
    Pain 07/1998; 76(3):327-36. · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In urethane-chloralose anesthetized Japanese macaques, the distribution of nociceptive neurons within the thalamic ventrobasal (VB) complex was studied. Nociceptive specific (NS) and wide dynamic range (WDR) neurons were found in the periphery of the contralateral integument compartment of the VB complex. Thus, they formed a shell at the perimeter of this compartment with a somatotopic organization. The compartment consisted of large parts of nucleus ventralis posteromedialis (VPM) and nucleus ventralis posterolateralis, pars caudalis (VPLc). NS neurons were located more caudally than WDR neurons. In the NS zone of VPM, the forehead was represented caudally, and oral structures rostrally. In the ventral NS zone of VPM, there was a sequential representation of the tongue, gum and mandibular skin from the medial to the lateral edge. The hand was represented medially in the NS zone of VPLc, and its representation dominated in the rostral NS zone. There was a sequential representation of the cervical, thoracic, lumbar, sacral and caudal segments mediolaterally along the dorsal VPLc. In the medial half of ventral NS zone of VPLc, the upper body half was represented, and in the lateral half, the lower body half. The foot was represented at or near the medial edge of lateral half. In the rostral WDR zone, the trunk and peripheral face were represented.
    Neuroscience Research 06/1998; 31(1):39-51. · 2.20 Impact Factor
  • Journal of Biotechnology 05/1998; 61(3):231-233. · 3.18 Impact Factor
  • Source
    J Chen, N Koyama
    [Show abstract] [Hide abstract]
    ABSTRACT: In our previous report we found that subcutaneous (s.c.) formalin injection into the cutaneous receptive field (RF) of dorsal horn wide-dynamic-range (WDR) units and nociceptive primary afferent units resulted in a tonic, long-lasting increase in firing. However, s.c. formalin injection only resulted in a short-lasting increase in firing of non-nociceptive primary afferent units. In the present study, by using extracellular single-unit recording techniques we further studied effects of s.c. formalin on response properties of identified superficial-layer nociceptive-specific (NS) units and deeper-layer, low-threshold mechanoreceptive (LTM) units of L7 dorsal horn in urethane-chloralose-anesthetized cats. s.c. formalin injection into the RF of NS units resulted in a tonic, long-lasting increase in firing (7.08+/-0.42 spikes/s, n = 5), for more than 1 h, compared with the spontaneous background (1.42+/-0.03 spikes/s, n = 5). Formalin injection into the RF of LTM units also resulted in an increase in firing; however, the duration was short-lasting, for 25-520 s (152.92+/-46.73 s, n = 12). The present study demonstrated that s.c. injection of dilute formalin solution resulted in activation of not only nociceptive but also non-nociceptive dorsal horn units, suggesting that tissue injury caused by s.c. formalin results in vigorous injury discharges of peripheral nerve terminals, which subsequently leads to activation of primary afferent neurons and secondary dorsal horn neurons.
    Experimental Brain Research 02/1998; 118(1):14-8. · 2.22 Impact Factor
  • Journal of Econometrics 01/1998; 89(1). · 1.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to investigate whether melittin, the principal toxin of the honeybee (Apis mellifera) venom, can be used as an algogenic agent in the study of pain in humans. Five micrograms of melittin in 0.5 ml of saline was intradermally injected into the volar aspect of the forearm. Resultant pain was scored by a visual analogue scale (VAS), and skin temperature change was analyzed by means of a computer-assisted infrared thermography. Intradermal melittin temporarily produced severe pain, followed by a sustained increase in skin temperature. The skin temperature increase peaked in about 10 min and outlasted 1 h. Topical application of 10% lidocaine gel did not significantly suppress the melittin-induced pain, but markedly suppressed both the increase in the peak temperature and the area of temperature increase. In conclusion, 5 mg of melittin is sufficient to produce pain in humans and 10% lidocaine gel differentially decreases the melittin-induced axon reflex without any significant analgesic effect. q 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.
    Neuroscience Research 01/1998; 31. · 2.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PurposeTo clarify whether ketamine suppresses both A-fiber-and C-fiber-mediated pain and to compare the effects of ketamine with those of MK-801. MethodsExperiments were performed on urethane/chloralose-anesthetized cats. Glass capillary microelectrodes were used to record extracellular single unit activities from wide dynamic range (WDR) neurons in the spinal dorsal horn. Responses evoked by electrical stimulation of the superficial peroneal (SP), posterior tibial (PT), or both nerves were analyzed. The responses to successive electrical stimuli were displayed on a personal computer using a raster-dot processing program. ResultsA subanesthetic dose of intravenous ketamine suppressed both A- and C-fiber responses of WDR neurons in a dose-dependent manner without affecting A-fiber response of low-threshold mechanoreceptive (LTM) neurons. The C-fiber response was more markedly suppressed than the A-fiber response. Intravenous administration of MK-801, a specificN-methyl-d-aspartate (NMDA) antagonist, selectively suppressed the C-fiber response of WDR neurons. ConclusionIntravenous ketamine may suppress both A-and C-fiber-mediated pain at a subanesthetic dose. This finding could be a scientific basis for the usefulness of ketamine during clinical procedures such as dressing changes or débridement of the burned patient.
    Journal of Anesthesia 07/1997; 11(3):184-192. · 0.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is well known that locus coeruleus (LC) of the rat shows intense μ-opioid receptor-like immunoreactivity (MOR-LI). In the course of our study on the distribution of MOR-LI in the brain of the Japanese monkey (Macaca fuscata), however, no MOR-LI was found in the LC although the distribution pattern of MOR-LI in other regions of the lower brainstem of the monkey was essentially the same as that observed in the rat. It was also found that immunoreactivity for Met-enkephalin, the most potent endogenous ligand for MOR, was intense in the rat LC, but very weak, if any, in the monkey LC. MOR may not be expressed in the monkey LC.
    Brain Research 05/1997; 755(2):326-330. · 2.88 Impact Factor
  • Neuroscience Research 01/1997; 28. · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The medulla oblongata caudal to the obex was explored for neurons responsive to tooth pulp (TP) stimulation in cats. Four different classes of TP neurons were found. They were TP specific neurons, trigeminal wide dynamic range neurons with TP input, trigeminal subnucleus reticularis ventralis (SRV) neurons with TP input and convergent reticular formation with TP input. They were differentially distributed within the caudal medulla oblongata.
    Brain Research 05/1996; 715(1-2):230-4. · 2.88 Impact Factor
  • Y Fujino, N Koyama, T Yokota
    [Show abstract] [Hide abstract]
    ABSTRACT: Nociceptive neurons within the reticular formation (RF) caudal to the obex were studied. 197 units recorded from the lateral part of subnucleus reticularis ventralis had receptive fields in the head, 72 units recorded from the medial RF in the body, and 160 units recorded from the middle third of RF in the head and body. About half of the units tested were antidromically excited by stimulation of nucleus centralis lateralis.
    Brain Research 05/1996; 715(1-2):225-9. · 2.88 Impact Factor
  • T Minami, N Koyama, Y Amakata
    [Show abstract] [Hide abstract]
    ABSTRACT: Lidocaine (1%), either in plain distilled water or in 10% dextrose, was intrathecally or epidurally administered to urethane-chloralose anesthetized cats. Electrical stimulation was applied to the gracile tract at a cervical level, and the resultant antidromic compound action potentials were recorded from the sural nerve. Lidocaine dissolved in plain distilled water was more effective than lidocaine dissolved in 10% dextrose solution in suppressing the compound action potentials. Lidocaine-free plain distilled water or dextrose solution caused partial suppression of the compound action potentils. The suppression was more marked following plain distilled water application than following application of 5% or 10% dextrose.
    Journal of Anesthesia 03/1996; 10(1):39-43. · 0.87 Impact Factor
  • Neuroscience Research 01/1996; 25. · 2.20 Impact Factor
  • Source
    K Hirata, N Koyama, T Minami
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of intravenous clonidine and tizanidine on nociceptive neurons in the nucleus ventralis posterolateralis (VPL) of the thalamus, a key station in the lateral system of ascending pain pathways, were evaluated in urethane-chloralose anesthetized cats. Intravenous clonidine and tizanidine produced a dose-dependent (5 and 10 micrograms/kg, and 25 and 50 micrograms/kg, respectively) suppression of responses of nociceptive specific (NS) and wide dynamic range (WDR) neurons in the VPL to high threshold splanchnic input. In contrast, the responses of both NS and WDR units to electrical stimulation of spinothalamic tract fibers in the ventrolateral funiculus (VLF) were little affected. We conclude that a site of suppressive action of the alpha 2-adrenoceptor agonists, as observed in nociceptive VPL neurons, is at the level of the spinal dorsal horn rather than in the VPL itself.
    Anesthesia & Analgesia 09/1995; 81(2):259-64. · 3.30 Impact Factor

Publication Stats

180 Citations
76.59 Total Impact Points

Institutions

  • 1997–2012
    • Shiga University of Medical Science
      • • Department of Physiology
      • • Department of Anesthesiology
      Ōtu, Shiga, Japan
  • 2001
    • Kissei Pharmaceuticals Co., Ltd.
      Shonai, Nagano, Japan
  • 1993–1999
    • Osaka Dental University
      • Department of Physiology
      Hirakata, Ōsaka, Japan