• YAKHAK HOEJI
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• v.43 no.4
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• pp.411-418
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• 1999

Intracerebroventricular (ICV) infusion of morphine (MOR) produces strong analgesia in man and animals. The analgesic effect is thought to be mediated by the centrifugal inhibitory control. But neural mechanisms of the analgesic effect of ICV morphine are not well understood. In the present study, we found that ICV MOR had dual actions on the activity of dorsal horn heurons: it produced both inhibition and excitation of dorsal horn neurons. Since MOR exerts its action via three different types of opioid receptors, we further sought to investigate if there are differential effects of opioid receptor agonists on dorsal horn neurons when administered intracerebroventricularly. Effects of ICV MOR were tested in 28 dorsal horn neurons of the spinal cord in the cat. ICV MOR inhibited, excited and did not affect the heat responses of dorsal horn neurons. ICV DAMGO and DADLE, $\mu$- and $\delta$-opioid agonist, respectively, exhibited the excitation of dorsal horn neurons. In contract, U-50488, a k-opioid agonist, exhibited both the inhibition and excitation of dorsal horn neurons. These results suggest that opioid receptors have different actions on activity of dorsal horn neuron and that the inhibitory action of k-opioid agonist may subserve the analgesia often produced by ICV MOR.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.303-303
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• 1994

ICV infusion of morphine (MOR) produces strong analgesia in man and animals. The analgesic effect is thought to be mediated by the centrifugal inhibtory control, But neural mechanisms of the analgesic effect of ICV morphine are not well understood. For example, in the previous studies, ICV morphine does not inhibit nociceptive transmission in the spinal cord. On the contrary, ICV MOR often excites activity of dorsal horn neuron in the spinal cord. In the present study, we found that ICV MOR had dust actions on activity of dorsal horn neuron that it produced both inhibition and excitation of dorsal horn neurons. Since MOR exerts i Is action via three different types of opioid receptors, we further sought to investigate if there are differential effects of opioid receptor agonists on dorsal horn neurons when administered ICV.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.404-410
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• 1999

Administration of capsaicin produces acute pain and subsequent long-lasting antinociception. The antinociceptive action site of capsaicin is primarily small afferent nerve fibers. However, the effect of capsaicin on the neural activity of dorsal horn neurons are not well understood. The goal of the present experiment was to study the action of capsaicin on activity of dorsal horn neurons using c-fos immunoreactivity in the spinal cord. Intradermal injection of formalin in the hindpaw produced inflammation in the foot pad and increased the number of cells exhibiting Fos-like immunoreactivity (FLI) in the dorsal horn of the spinal cord, suggesting the hyperalgesia because of the apparent inflammation. Intradermal injection of capsaicin prior to formalin injection significantly reduced the number of cells exhibiting FLI induced by formalin and increased the paw-withdrawal latency, suggesting the hypoalgesic effect of capsaicin. Coadministeration with capsaicin of capsazepine and ruthenium red, antagonists of capsaicin receptor reversed the reduction of formalin-induced FLI by capsaicin. he antagonists also partially antagonized the antinociceptive effect of capsaicin in the paw-withdrawal test. These results further suggest that capsaicin reduces prsponses of dorsal horn neurons to the inflammatory nociceptive stimuli in the periphery. Thus, the reduction of FLI subserves the neural mechanisms underlying analgesia produced by capsaicin.

• The Korean Journal of Pain
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• v.19 no.1
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• pp.22-32
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• 2006

Background: This study was conducted to investigate the roles of the spinal and peripheral ${\gamma}$-aminobutyric acid (GABA)- ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). Methods: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. Results: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. Conclusions: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.37-43
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• 1993

Electrical or chemical stimulation of many areas in the brainstem modulates activity of dorsal horn neurons (DHN). This is known to be mediated by a population of bulbospinal neurons. Yet, little is known about responses of DHNs to stimulation of the caudal ventrolateral medulla (CVLM). Thus, the purpose of the present study is to see if there is any change in activity of DHNs when CVLM is stimulated electrically. Thirty-one DHNs were recorded from dorsal horn of the spinal cord. Fourteen DHNs (45%) were classified as wide dynamic range neurons and 9 (19%) were high threshold cells, and 4 (13%) and 4 (13%) were deep and low threshold neurons, respectively. Among 31 neurons tested for responses to stimulation of CVLM, 21 DHNs (68%) were inhibited by the electrical stimulation of CVLM ($200{\mu}A,\;100{\mu}s$ duration, 100 Hz), and 9 cells (39%) did not show any change in neuronal activity. One neuron was excited by the stimulation. The electrical stimulation of CVLM not only inhibited spontaneous activity of DHNs but also inhibited evoked responses of DHNs to somatic stimulation in the receptive field. These data suggest that CVLM is one of the pain-modulatory areas that control transmission of ascending information of noxious input to the brain from the spinal cord.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.19-30
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• 2000

Background: Partial nerve injury to a peripheral nerve may induce the development of neuropathic pain which is characterized by symptoms such as spontaneous burning pain, allodynia and hyperalgesia. Though underlying mechanism has not fully understood, sensitization of dorsal horn neurons may contribute to generate such symptoms. Nitric oxide acts as an inter- and intracellular messenger in the nervous system and is produced from L-arginine by nitric oxide synthase (NOS). Evidence is accumulating which indicate that nitric oxide may mediate nociceptive information transmission. Recently, it has been reported that NOS inhibitor suppresses neuropathic pain behavior in an neuropathic pain animal model. This study was conducted to determine whether nitric oxide could be involved in the sensitization of dorsal horn neurons in neuropathic animal model. Methods: Neuropathic animal model was made by tightly ligating the left L5 and L6 spinal nerves and we examined the effects of iontophoretically applied NOS inhibitor (L-NAME) on the dorsal horn neuron's responses to mechanical stimuli within the receptive fields. Results: In normal animals, NOS inhibitor (L-NAME) specifically suppressed the responses to the noxious mechanical stimuli. In neuropathic animals, the dorsal horn neuron's responses to mechanical stimuli were enhanced and NOS inhibitor suppressed the dorsal horn neuron's enhanced responses to non-noxious stimuli as well as those to noxious ones. Conclusions: These results suggest that nitric oxide may mediate nociceptive transmission in normal animal and also mediate sensitization of dorsal horn neurons in neuropathic pain state.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.77-86
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• 2005

In this study, we examined the morphine-induced modulation of the nociceptive spinal dorsal horn neuronal activities before and after formalin-induced inflammatory pain. Intradermal injection of formalin induced time-dependent changes in the spontaneous activity of nociceptive dorsal horn neurons. In naive cats before the injection of formalin, iontophoretically applied morphine attenuated the naturally and electrically evoked neuronal responses of dorsal horn neurons. However, neuronal responses after the formalin-induced inflammation were significantly increased by morphine. Bicuculline, $GABA_A$ antagonist, increased the naturally and electrically evoked neuronal responses of dorsal horn neurons. This increase in neuronal responses due to bicuculline after the formalin-induced inflammation was larger than that in the naive state, suggesting that basal $GABA_A$ tone increased after the formalin injection. Muscimol, $GABA_A$ agonist, reduced the neuronal responses before the treatment with formalin, but not after formalin treatment, again indicating an increase in the GABAergic basal tone after the formalin injection which saturated the neuronal responses to GABA agonist. Morphine-induced increase in the spinal nociceptive responses after formalin treatment was inhibited by co-application of muscimol. These data suggest that formalin-induced inflammation increases $GABA_A$ basal tone and the inhibition of this augmented $GABA_A$ basal tone by morphine results in a paradoxical morphineinduced increase in the spinal nociceptive neuronal responses after the formalin-induced inflammation.

• Journal of Korean Physical Therapy Science
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• v.7 no.2
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• pp.545-558
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• 2000

The present study was designed to investigate the effect of low power GaAsAl laser on Fos expression in the spinal cord induced by noxious mechanical stimulation. Noxious mechanical stimulation was applied to the right hind paw following 30min of low power laser treatment using different intensity and treatment point and the resulting Fos expression in the spinal cord dorsal horn was compared to that obtained in rats exposed only to the noxious mechanical stimulation. The results were summarized as follows: 1. In intact control rats, only a few Fos like immunoreactive(Fos-IR) neurons were evident in the lumbar spinal cord dorsal horn. Similarly, following prolonged inhalation anesthesia, Fos-IR neurons were absent in the dorsal horn of the lumbar spinal cord. In animals treated with noxious mechanical stimulation, neurons with nuclei exhibiting Fos immunostaining were distributied mainly in the medial half of ipsilateral laminae I-V at lumbar segments L3-5. These findings directly indicated that prolonged anesthesia used in this study did not affect the Fos expression in the spinal cord dorsal horn of intact animals and noxious mechanical stimulation treated animals. 2. In acupoint treated animals, 10mW of laser stimulation, not 3mW intensity, significantly reduced the number of Fos immunoreactive neurons in the spinal dorsal horn induced by noxious mechanical stimulation(P<.01). However, the supressive effect of low power laser stimulatin was not observed in 3m Wand 10m W of laser stimulation into non-acupoint. These data indicate that 10mW of low power laser stimulation into acupoint is capable of inhibiting the expression of Fos in the dorsal horn induced by noxious mechanical stimulation. In conclusion, these findings raise the possibility that low power laser stimulation into acupoint may be a promising alternative medicine therapy for the mechanical stimulation induced pain in the clinical field.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.283-292
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• 1996

The spinal dorsal horn is the area where primary afferent fibers terminate and cutaneous sensory information is processed. A number of putative neurotransmitter substances, including excitatory and inhibitory amino acids and peptides, are present in this region. In this study, single neurons of the spinal dorsal horn were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by patch clamp technique. Transverse slice ($(300{\mu}m$) of lumbar spinal cords from young rats$(7{\sim}14\;days)$ were sequentially treated with two pretenses(pronase 0.75 mg/ml and thermolysin 0.75 mg/ml), then single neurons were mechanically dissociated. These neurons showed near-intact morphology such as multipolar, ellipsoidal and bipolar, and pyramidal cells and we recorded the typical whole cell currents of $K^+$, $Ca^{2+}$ and ligand-operated channels from these neurons. Glutamate $(30{\mu}M)$ and N-methyl-D-aspartate(NMDA, $30{\mu}M)$ induced inward currents of $117{\pm}12.4$ pA(n=5) and $49{\pm}6.9$ pA(n=3), respectively. Glycine $(1{\mu}M)$ potentiated glutamate-induced currents $4{\sim}5$ times and NMDA-induced currents $8{\sim}10$ times. In addition, glycine $(30{\mu}M)$ induced Inward current ($31{\pm}6.1$ nA, n=2), which was rapidly desensitized after the peak to a new steady-state level. However, the inward currents induced by ${\gamma}-amino$ butyric acid(GABA, $1{\mu}M$) decreased continuously after the peak($226{\pm}41.6$ pA, n=3) under the similar experimental condition. The ionic currents and pharmacological responses of isolated neurons in this work were similar to those observed in vivo or in vitro spinal cord slice, indicating that acutely isolated neurons could be effectively used for further pharmacological studies.

• The Journal of Korean Physical Therapy
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• v.15 no.4
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• pp.299-311
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• 2003

The purpose of this study is to investigate and analysis effect of TENS with immunohistochemistry methode through changes of substance P in spinal using arthritis model after inducing inflammation. The changes of substance P induced at that time are compared with control which is not induced arthritis by means of counting. The effect of TENS (4Hz, $200{\mu}$, 20minutes) is also tested by observing changes of substance P in spinal dorsal horn after application on knee joint of rats which is arthritis model induced by kaolin and carrageenan. The results of this study were as follows: 1. Substance P immunoreactive positive neurons are increased in dorsal horn after inducting arthritis. 2. In arthritis group, Substance P immunoreactive positive neurons are progressively increased from the first to the third days. 3. Substance P immunoreactive positive neurons after applicating TENS on arthritis group are more decreased than only arthritis-induced group. 4. Substance P immunoreactive positive neurons were significantly decreased on the second days resulting from TENS application from the first to the third days. Therefore, TENS application is decrease Substance P immunoreactive positive neurons in spinal dorsal horn of rats induced arthritis. This decrease is considered as analgesic effect of TENS.