• 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.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.749-752
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• 2005

We investigated the effects of electroacupuncture (EA) on the expression of cyclooxygenase in the spinal cord of acute inflammatory pain model. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw of Sprague-Dawley. Bilateral 2 Hz EA stimulation with 0.5 mA, 1 mA and 3 mA were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles in carrageenan-injected rats. Three hours after carrageenan injection, effects of EA on cyclooxygenase (COX) expression were observed in the dorsal horn of the spinal cord using immunohistochemical method. The immunoreaction of COX-1 tended to increase in the superficial laminae and the neck of the dorsal horn as compared with normal. The COX-2 immunoreaction in the carrageenan-injected rat was also significantly increased in the all regions of the dorsal horn as compared with normal one. However, COX-1 immunoreaction in carrageenan-injected rat were decreased in the superficial laminae and neck of the dorsal horn by low intensity of EA stimulation. Except high intensity of EA stimulation in the superficial laminae, COX-2 expression was attenuated in all regions of the dorsal horn by all types of EA treatment. It is concluded that EA treatment may attenuate inflammatory pain in carrageenan-injected rat through modulating expression of COX-2 in the dorsal horn of the spinal cord.

• Journal of Korean Physical Therapy Science
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• v.8 no.2
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• pp.1005-1013
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• 2001

The present study was designed to investigate the effect of low power GaAlAs laser on spinal Fos expression related to the anti-nociceptive effect of laser stimulation. Low power GaAlAs laser was applied to either acupoint or non-acupoint for 2 hour under light inhalation anesthesia. Spinal Fos expression in the dorsal horn was compared to that obtained in inhalation anesthesia control group. Furthermore, we analyzed the effect of the local treatment of lidocaine on the spinal Fos expression evoked by low power GaAlAs laser stimulation. The results were summarized as follows: 1. In the normal animals, 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 laser stimulation, Fos immunoreactive neurons were increased mainly in the medial half of ipsilateral laminae I-III 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 low power laser stimulation dramatically produced Fos expression in the spinal cord laminae that are related to the anti-nociceptive effect of laser stimulation. 2. In acupoint stimulated animals, 10mW of laser stimulation, not 3mW and 6mW intensity, significantly increased the number of Fos immunoreactive neurons in the spinal dorsal horn(p<0.05). However, laser stimulation on acupoint more dramatically increased the number of Fos immunoreactive neurons in the spinal cord rather than laser stimulatin on non acupoint. These result suggested that laser stimulatin on acupoint was more effective treatment to activate the spinal neuron than non acupoint stimulation. 3. The local treatment of lidocaine totally suppressed the activity of spinal neurons that were induced by lower power 1aser stimulation. These data indicated that the anti-nociceptive effect of laser stimulation was absolutely dependent upon the peripheral nerve activity in the stimulated location. In conclusion, these data indicate that 10mW of low power laser stimulation into acupoint is capable of inducing the spinal Fos expression in the dorsal horn related to the anti-nociceptive effect of laser stimulation, Furthermore, the induction of spinal Fos expression was totally related to the peripheral nerve activity in the laser stimulated area.

• 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.

• Journal of Korean Neurosurgical Society
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• v.29 no.7
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• pp.877-885
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• 2000

Objective : The NOS inhibitors exhibit antinociceptive activity in rat model of neuropathic pain. NOS activity increases in the dorsal root ganglia(DRG) in neurop-athic pain. However, NOS activity decreases in the dorsal horn of spinal cord in the nerve injury models of neuropathic pain. To investigate whether the mechanism of decrease of NOS expression in the dorsal horn is related to a secondary effect resulting from increased NO production and likewise in the spinal DRG in the spinal nerve ligation model of neuropathic pain. Methods : We conducted behavioral tests for neuropathic pain, and nNOS immunohistochemistry and NADPH-diaphorase histochemistry after tight ligation of the 5th lumbar(L5) and 6th lumbar(L6) spinal nerves and L5 dorsal rhizotomy. Results : Typical neuropathic pain behaviors occurred 7 days after post-ligation in the neuropathic surgery group, but neuropathic pain behaviors in the dorsal rhizotomy group were absent or weak 7 days after post-operation. There was a decrease in the number of nNOS immunoreactive dorsal horn neurons on the both side(especially ipsilateral side) 7 days after post-ligation. The number of nNOS immunoreactive neurons in both side of the dorsal horn was not decreased 7 days after L5 dorsal rhizotomy. Conclusion : These data indicate that the changes in the injured DRG is essential for development and maintenance of neuropathic pain, and mechanism of decrease of nNOS expression in the dorsal horn is a secondary effect against the changes in the DRG including increased NO production in the spinal nerve ligation model of neuropathic pain.

• 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 Journal of Korean Physical Therapy
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• v.16 no.2
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• pp.169-180
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• 2004

The aim of this study was to investigate the effect of TENS on muscle pain induced by carrageenan. Muscle pain was induced in male Sprague-Dowley rats by intra-muscular injection of gastrocnemius with $3\%$ carrageenan. nNOS was measured to assess the effect of TENS on muscle pain induced by Carrageenan. The lumbar enlargement of the spinal cord was removed in different groups of animals 24 h after induction of muscle pain. The level of nNOS mRNA was measured in the lumbar section of the spinal cord using RT-PCT. The expression of nNOS was analyzed in the dorsal horn of the lumbar spinal cord by immunohistochemistry. TENS decreased nNOS immunoreactivity in the dorsal horn of the lumbar spinal cord when compared with controls(p<.05). In RT-PCR, TENS decreased nNOS mRNA level of lumbar spinal cord when compared with controls(p<.05). These results suggested that application of TENS attributed to decrease muscle 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.

• Animal cells and systems
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• v.4 no.4
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• pp.353-359
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• 2000

Location of the neurons in the lateral reticular nucleus projecting to dorsal horn of the cervical, thoracic, or lumbar spinal cord was investigated in the rat using the technique of retrograde transport of horseradish peroxidase. The projection was bilateral with ipsilateral predominance. Neurons projecting to the cervical spinal cord were located near the medial, dorsal, and lateral perimeter of the magnocellular division of the lateral reticular nucleus, whereas cells projecting to the thoracic and lumbar spinal cord were localized in the medial and dorsal boundaries of the magnocellular division. The labeled neurons were distinctly multipolar in shape and measured approximately 10-15 $\mu m$ in their greatest transverse diameter. A few neurons were also observed in the subtrigeminal nucleus, whereas few cells were in the parbocellular division. These observations provide an anatomical substrate for the functional implication of the lateral reticular nucleus in the regulation of spinal nociceptive transmission and vascular hemodynamics via the descending pathway into the spinal cord.