• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.143-147
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• 2005

Following peripheral nerve injury, excessive nociceptive inputs result in diverse physiological alterations in the spinal cord substantia gelatinosa (SG), lamina II of the dorsal horn. Here, I report the alterations of excitatory or inhibitory transmission in the SG of a rat model for neuropathic pain ('spared nerve injury'). Results from whole-cell recordings of SG neurons show that the number of distinct primary afferent fibers, identified by graded intensity of stimulation, is increased at 2 weeks after spared nerve injury. In addition, short-term depression, recognized by paired-pulse ratio of excitatory postsynaptic currents, is significantly increased, indicating the increase of glutamate release probability at primary afferent terminals. The peripheral nerve injury also increases the amplitude, but not the frequency, of spontaneous inhibitory postsynaptic currents. These data support the hypothesis that peripheral nerve injury modifies spinal pain conduction and modulation systems to develop neuropathic pain.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.113-122
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• 1994

The present study was carried out to characterize the functional properties of spinomesencephalic tract (SMT) neurons in the lumbar spinal cord of urethane anesthetized rats. Extracellular single unit recordings were made from neurons antidromically activated by stimulation of the midbrain area, including the deep layers of superior colliculus, periaqueductal gray and midbrain reticular formation. Recording sites were located in laminae I-VII of spinal cord segments of L2-L5. Receptive field properties and responses to calibrated mechanical stimulation were studied in 78 SMT cells. Mean conduction velocity of SMT neurons was $19.1{\pm}1.04\;m/sec$. SMT units were classified according to their response profiles into four groups: wide dynamic range (58%), deep/tap (23%), high threshold (9%) and low threshold (3%). A simple excitatory receptive field was found for most SMT neurons recorded in superficial dorsal horn (SDH). Large complex inhibitory and/or excitatory receptive fields were found for cells in lateral reticulated area which usually showed long after-discharge. Most of SMT cells received inputs from $A{\delta}$ and C afferent fiber types. These results suggest that sensory neurons in the rat SMT may have different functional roles according to their location in the spinal cord in integrating and processing sensory inputs including noxious mechanical stimuli.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.253-258
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• 2008

Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the $A{\delta}$ -and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and $A{\delta}$-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

• International Journal of Oral Biology
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• v.32 no.4
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• pp.153-160
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• 2007

The superficial dorsal horn, particularly substantia gelatinosa (SG) in the spinal cord, receives inputs from small-diameter primary afferents that predominantly convey noxious sensation. Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS are also involved in persistent pain through a spinal mechanism. In the present study, whole cell patch clamp recordings were carried out on SG neurons in spinal cord slice of young rats to investigate the effects of hydrogen peroxide on neuronal excitability and excitatory synaptic transmission. In current clamp condition, tert-buthyl hydroperoxide (t-BuOOH), an ROS donor, depolarized membrane potential of SG neurons and increased the neuronal firing frequencies evoked by depolarizing current pulses. When slices were pretreated with phenyl-N-tert-buthylnitrone (PBN) or ascorbate, ROS scavengers, t-BuOOH did not induce hyperexcitability. In voltage clamp condition, t-BuOOH increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), and monosynaptically evoked excitatory postsynaptic currents (eEPSCs) by electrical stimulation of the ipsilateral dorsal root. These data suggest that ROS generated by peripheral nerve injury can modulate the excitability of the SG neurons via pre- and postsynaptic actions.

• The Journal of Korean Physical Therapy
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• v.19 no.2
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• pp.41-55
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• 2007

Purpose: This study aimed to compare the effect on nerve regeneration of ultrasound irradiation in rats with peripheral nerve injury. Methods: To investigate alterations of the NCAM immunoreactivity in non-crushed part and crushed part of the spinal cord, the unilateral sciatic nerve of the rats were crushed. The expression of NCAM was used as the marked of peripheral nerve regeneration, and also plays an important role in developing nerve system. Experimental animals were sacrificed by perfusion fixation at post-injury 1, 3, 7, 14 days after ultrasound irradiation. The pulsed US was applied at a frequency of 1MHz and a spatial average-temporal average Intensity of 0.5W/of (20% pulse ratio) for 1 mins. The Luxol fast blue-cresyl violet stain were also done to observe the morphological changes. Results: Alteration of NCAM immunoreactivity in the crushed part and the non-crushed part of lower lumbar spinal cord were observed. NCAM-immunoreactivity cells were some increased in the dorsal horn lamina I, III and cell ventral horn at 1 day after unilateral sciatic nerve injury. However, there was not significant difference in the relationship between crushed part and non-crushed part. NCAM-inmmunoreactivity was remarkably increased at 3 days after unilateral sciatic nerve injuryin the gray matter and white matter. NCAM-immunoreactivity was increased in the ventral horn and post horn of experimental crushed part. Also, NCAM-immunoreactivity in large motor neurons in ventral horns lamina VIII, IX were increased at 7 days after unilateral sciatic nerve injury. At 14 days after sciatic nerve crushed injury, there was no significant difference. All group were decreased for 14 days. In the time course of NCAM expression, all groups showed a significant difference at 3day groups(p<0.05). Whereas, CC group was noted a significant difference between 3day and 7 day group respectively. In NCAM expression, there were significantly increased in all group. In the relationship between CNC group and ENC group, significant difference was detected among 3, 7, 14 day group(p<0.05). The difference between CC group and ENC group were noted in all groups(p<0.05). Conclusion: It is consequently suggested that the effects of the ultrasound irradiation may increase the NCAM immunoreactive neurons and glial cell in the spinal cord after unilateral sciatic nerve crushed injury. Therefore, the increased NCAM immunoreactivity in the spinal cord may reflect the neuronal damage and healing process induced by a ultrasound irradiation after peripheral nerve injury in rat.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.455-461
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• 2000

Zinc contained in the neurons of central nervous system is activity-dependently released and then attenuates NMDA (N-methyl-D-aspartate)-induced neurotoxicity while augmenting non-NMDA-induced neurodegeneration. Zinc also has been reported to produce antinociceptive action on the inflammation- and nerve injury-induced hyperalgesia in the behavioral test. In this study, we investigated the effects of zinc on the responses of dorsal horn cells to NMDA, kainate and graded electrical stimulation of C-fibers. In the majority of WDR cells (70.6%), zinc current-dependently inhibited WDR cell responses to NMDA and in the remaining cells, produced biphasic responses; excitation followed by inhibition. Zinc augmented the responses of WDR cells to iontophoretical application of kainate. The dominant effect of $Zn^{2+}$ on the responses of WDR cells to C-fiber stimulation was excitatory, but inhibition, excitation-inhibition and no change of the responses to C-fiber stimulation were induced. $Ca^{2+}-EDTA$ antagonized the excitatory or inhibitory effects of $Zn^{2+}$ on the WDR cell responses. These experimental findings suggest that $Zn^{2+}$ modulates the transmission of sensory information in the rat spinal cord.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.553-558
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• 2013

Spinal dorsal horn nociceptive neurons have been shown to undergo long-term synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). Here, we focused on the spinothalamic tract (STT) neurons that are the main nociceptive neurons projecting from the spinal cord to the thalamus. Optical technique using fluorescent dye has made it possible to identify the STT neurons in the spinal cord. Evoked fast mono-synaptic, excitatory postsynaptic currents (eEPSCs) were measured in the STT neurons. Time-based tetanic stimulation (TBS) was employed to induce long-term potentiation (LTP) in the STT neurons. Coincident stimulation of both pre- and postsynaptic neurons using TBS showed immediate and persistent increase in AMPA receptor-mediated EPSCs. LTP can also be induced by postsynaptic spiking together with pharmacological stimulation using chemical NMDA. TBS-induced LTP observed in STT neurons was blocked by internal BAPTA, or $Ni^{2+}$, a T-type VOCC blocker. However, LTP was intact in the presence of L-type VOCC blocker. These results suggest that long-term plastic change of STT neurons requires NMDA receptor activation and postsynaptic calcium but is differentially sensitive to T-type VOCCs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.117-123
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• 2002

To investigate the antiinflammatory and analgesic effects of Sophorae radix extracts administered to the arthritic rat model, immunohistochemical stains for CGRP in the L4, L5 and L6 spinal cord and ganglia were done, and paw swelling thickness were measured. Complete Freund,s Adjuvant(CFA) were injected to subcutaneous tissue of left foot paw of rats to induce arthritis. Sophorae radix extracts was administered immediately after CFA injection for 10 days. The spinal cord and ganglia were frozen sectioned(30㎛). These sections were stained by CGRP immunohistochemical staining method, and observed with light microscope. The results were as follows : 1. The change of paw swelling thickness of experimental group decreased from 4 day to 10day after CFA injection compared to control group. 2. The change of differential leukocytes counts of experimental group increased the ratio of lymphocytes. and decreased the ratio of neutrophils compared to control group. 3. The change of CGRP immunoreactive nerve fiber of dorsal horn of experimental group was dense stained compared to control group. 4. The number of CGRP immunoreactive neurons of L4 and L5 spinal cord of experimental group was less than in those control group. These results suggested that Sophorae radix extracts reduces the number of CGRP immunoreactive neurons and nerve fibers of spinal cord and ganglia, and decrease paw swelling thickness in arthritic rat model, which may be closely related to analgesic and antiinflammatory effects of Sophorae radix.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.33-41
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• 1993

Central analgesic effect of capsaicin was assessed by the tail flick reflex (TFR) test, using male Sprague-Dawley rats under anesthesia with pentobarbital sodium (induction with 40 mg/kg and maintenance with $4{\sim}8\;mg/kg/hr$). Level of norepinephrine in the spinal cord was also measured. Capsaicin, $35{\sim}150\;{\mu}g$, was injected intrathecally, and the TFR latency was measured before, 10, 30, and 60 minutes after the drug administration. TFR latency was increased 100% or more immediately by intrathecal capsaicin, from 2.9 seconds to the maximum of 7.0 seconds at 10 minute after the drug; P<0.01. The increase in TFR latency was maintained during the course of experiment of 2 hours. Concomitant reduction of NE content in the spinal cord was observed; from 16 ng/mg protein to 7 ng/mg protein. On the other hand, subcutaneous injection of capsaicin of 50 mg/kg did not change the TFR latency although the NE content reduced similarly to the case of intrathecal injection. Pretreatment of the animal with 0.5 mg/kg of MK-801 reversed the increase of TFR latency and NE reduction induced by intrathecal capsaicin. These results suggest that capsaicin causes analgesia at the spinal cord level by activating the excitatory amino acid-NE-dorsal horn interneurons axis of the descending inhibitory pain modulation pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.9-19
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• 1998

The present study was primarily carried out to characterize the properties of the spinomesencephalic tract (SMT) neurons that project from the upper cervical spinal segments to the midbrain. It was also investigated whether these neurons received convergent afferent inputs from other sources in addition to cervical inputs. Extracellular single unit recordings were made from neurons antidromically activated by stimulation of midbrain. Recording sites were located in lamina $I{\sim}VIII\;of\;C1{\sim}C3$ segments of spinal cord. Receptive field (RF) and response properties to mechanical stimulation were studied in 71 SMT neurons. Response profiles were classified into six groups: complex (Comp, n=9), wide dynamic range (WDR, n=16), low threshold (LT, n=5), high threshold (HT, n=6), deep/tap (Deep, n=10), and non- responsive (NR, n=25). Distributions of stimulation and recording sites were not significantly different between SMT groups classified upon their locations and/or response profiles. Mean conduction velocity of SMT neurons was $16.7{\pm}1.28\;m/sec$. Conduction velocities of SMTs recorded in superficial dorsal horn (SDH, n=15) were significantly slower than those of SMTs recorded in deep dorsal horn (DDH, n=18), lateral reticulated area (LRA, n=21), and intermediate zone and ventral horn (IZ/VH, n=15). Somatic RFs for SMTs in LRA and IZ/VH were significantly larger than those in SDH and DDH. Five SMT units (4 Comps and 1 HT) had inhibitory somatic RFs. About half (25/46) of SMT units have their RFs over trigeminal dermatome. Excitabilities of 5/12 cells and 9/13 cells were modulated by stimulation of ipsilateral phrenic nerve and vagus nerve, respectively. These results suggest that upper cervical SMT neurons are heterogenous in their function by showing a wide range of variety in location within the spinal gray matter, in response profile, and in convergent afferent input.