• 동의생리병리학회지
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• 제16권2호
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• pp.272-278
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• 2002

To investigate the anti-inflammatory and analgesic effects of Herba Chelidoniie, the extracts of Herba Chelidoniie treated in arthritic rat model. Complete Freund,s Adjuvant(CFA) were injected in the subcutaneous tissue of left foot paw of rats to induce arthritis. Herba Chelidonii extracts(HC) was administered immediately into the peritoneal cavity after CFA injection for 12 days. The immunohistochemical stainings for calcitonin gene-related peptide(CGRP) and substance P in the L4, L5 and L6 spinal dorsal horn and ganglia were done, and the paw swelling was measured with a micrometer and the blood leukocytes were counted. The results were as follows : The paw swelling of HC treated group was significantly decreased in 12th day after CFA injection compare to control group. The change of differential leukocytes counts of HC treated group increased the ratio of lymphocytes, and decreased the ratio of neutrophils compare to control group. The extent of CGRP immunoreactive nerve fiber of dorsal horn of HC treated group was weakly stained compare to control group. The number of CGRP immunoreactive neurons of L6 spinal cord of HC treated group was significantly decreased compare to control group. The extent of substance P immunoreactive nerve fiber of dorsal horn of He treated group was weakly stained compare to control group. The number of substance P immunoreactive neurons of L4, L5 and L6 spinal cord of HC treated group was significantly decreased compare to control group. These experimental results suggest that Herba Chelidonii extracts reduce the number of CGRP and substance P immunoreactive neurons and nerve fibers of spinal dorsal horns and ganglia, and decrease paw swelling in arthritic rat model, which may be closely related to analgesic and antiinflammatory effects of Herba Chelidonii.

• The Korean Journal of Physiology
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• 제30권2호
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• pp.289-297
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• 1996

Excitatory amino acids (EAA) are thought to play an important role in producing cell death associated with ischemic and traumatic spinal cord injury. The present study was carried out to determine if the response characteristics of spinal sensory neurons in segments adjacent to degeneration sites induced by EAA are altered following these morphological changes. Intraspinal injections of quisqualic acid (QA) produced neuronal degeneration and spinal cavitation of gray matter. The severity of lesions was significantly attenuated by pretreatment with a non-NMDA antagonist NBQX. In extracellular single unit recordings, dorsal horn neurons in QA injected animal showed the increased mechanosensitivity, which included a shift to the left in the stimulus-response relationship, an increased background activity and an increase in the duration of after-discharge responses. Neuronal responses, especially the C-fiber response, to suprathreshold electrical stimulation of sciatic nerve also increased in most cases. These results suggest that altered functional states of neurons may be responsible for sensory abnormalities, e.g. allodynia and hyperalgesia, associated with syringomyolia and spinal cord injury.

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.155-163
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• 1998

The purpose of present study was to compare the effects of somatostatin (SOM) and morphine (Mor) on the responses of wide dynamic range (WDR) cells to peripheral noxious stimulation. Single neuronal activity was recorded with a carbon-filament electrode at the lumbosacral enlargement of cat spinal cord. After identifying WDR cells, their responses to peripheral noxious mechanical or thermal stimuli were characterized and the effects of SOM and Mor, applied either iontophoretically or intrathecally, were studied. In most cells SOM and Mor suppressed noxious stimulus-evoked WDR neuronal activity, though a few WDR neurons showed no change or were excited by SOM and Mor. Systemically applied naloxone, a non-specific opioid antagonist, always reversed the Mor induced suppression of neuronal activity evoked by noxious mechanical stimuli, but did not always reverse the suppression of neuronal activity elicited by SOM. The suppressive effect of Mor on thermal stimulus-evoked neuronal activity was partially reversed by naloxone, while that of SOM were not reversed at all. The above results suggest that both Mor and SOM exert an inhibitory effect on thermal and mechanical stimulus-evoked WDR neuronal activity in cat spinal dorsal horn, but the mechanisms are dependent upon the functional populations of dorsal horn nociceptive neurons.

• The Korean Journal of Pain
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• 제31권1호
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• pp.10-15
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• 2018

Background: To identify a new strategy for postoperative pain management, we investigated the analgesic effects of allopregnanolone (Allo) in an incisional pain model, and also assessed its effects on the activities of the primary afferent fibers at the dorsal horn. Methods: In experiment 1, 45 rats were assigned to Control, Allo small-dose (0.16 mg/kg), and Allo large-dose (1.6 mg/kg) groups (n = 15 in each). The weight bearing and mechanical withdrawal thresholds of the hind limb were measured before and at 2, 24, 48, and 168 h after Brennan's surgery. In experiment 2, 16 rats were assigned to Control and Allo (0.16 mg/kg) groups (n = 8 in each). The degree of spontaneous pain was measured using the grimace scale after the surgery. Activities of the primary afferent fibers in the spinal cord (L6) were evaluated using immunohistochemical staining. Results: In experiment 1, the withdrawal threshold of the Allo small-dose group was significantly higher than that of the Control group at 2 h after surgery. Intergroup differences in weight bearing were not significant. In experiment 2, intergroup differences in the grimace scale scores were not significant. Substance P release in the Allo (0.16 mg/kg) group was significantly lower than that in the Control group. Conclusions: Systemic administration of Allo inhibited mechanical allodynia and activities of the primary afferent fibers at the dorsal horn in a rat postoperative pain model. Allo was proposed as a candidate for postoperative pain management.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.661-670
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• 1998

Dopamine has been generally known to exert antinociceptive action in behavioral pain test, such as tail flick and hot plate test, but there appears to be a great variance in the reports on the antinociceptive effect of dopamine depending on the dosage and route of drug administration and type of animal preparation. In the present study, the effects of dopamine on the responses of wide dynamic range (WDR) cells to mechanical, thermal and graded electrical stimuli were investigated, and the dopamine-induced changes in WDR cell responses were compared between animals with an intact spinal cord and the spinal animals. Spinal application of dopamine (1.3 & 2.6 mM) produced a dose-dependent inhibiton of WDR cell responses to afferent inputs, the pinch-induced or the C-fiber evoked responses being more strongly depressed than the brush-induced or the A-fiber evoked responses. The dopamine-induced inhibition was more pronounced in the spinal cat than in the cat with intact spinal cord. The responses of WDR cell to thermal stimulation were also strongly inhibited. Dopamine $D_2$ receptor antagonist, sulpiride, but not $D_1$ receptor antagonist, significantly blocked the inhibitory action of dopamine on the C-fiber and thermal responses of dorsal horn cells. These findings suggest that dopamine strongly suppresses the responses of WDR cells to afferent signals mainly through spinal dopamine $D_2$ receptors and that spinal dopaminergic processes are under the tonic inhibitory action of the descending supraspinal pathways.

• The Journal of Korean Physical Therapy
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• 제15권4호
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• pp.190-198
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• 2003

Expression of c-fos, an immediate early gene, has accepted to be a marker of functional activity in neurons. This study was aimed to investigate the effects of cold therapy on the expression of spinal cord c-fos in rats of carrageenan-induced muscle pain. Muscle pain was induced in male Sprague-Dawley rats by intra-muscular injection of gastrocnemius with $2\%$ carrageenan. The paw withdrawal latency (PWL) and tail flick test (TFT) responses to heat stimuli were used to detect secondary hyperalgesia produced by the muscle pain and measured to assess the effects of cold. The expression of c-fos was determined in the lumbar regions of the spinal cord by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. The secondary hyperalgesia to heat simuli (PWL and TFT) were significantly reduced in cold therapy compared with that in the controls. In RT-PCR assays the expression of c-fos mRNA was down-regulated in the lumbar spinal cord in cold group. In addition, Fos immunoreactivity in the dorsal horn of the lumbar spinal cord was decreased in cold group. These results suggested that application of cold attributed to increase PWL and TFT responses and to decrease expression of the c-fos produced by muscle pain.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.175-175
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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 and sites and cellular mechanisms of their actions have been a target of numerous studies. In this study, single neurons were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by the patch clamp method. Young rats (7-14 days) were anesthetized with diethyl-ether, and the lumbar spinal cord was excised and cut transversely at a thickness of 30$\mu\textrm{m}$ by Vibroslicer. The treatment of spinal slices with low concentration of proteases (pronase and thermolysin 0.75 mg/$m\ell$) and mechanical dissociation yielded isolated neurons with near intact morphology. Multipolar, ellipsoidal and bipolar, and pyramidal cells were shown. By applying step voltage pulses to neurons held at -70 mV, two types of inward currents and one outward currents observed. The fast activating and inactivating inward current was the Na$\^$+/ current because of its fast kinetics and blocking by 0.5${\mu}$M TTX, a specific blocker of Na$\^$+/ channel. The second type of inward currents were sustained. Based on their kinetics and current-voltage relations, it was likely that the second type of inward current was the voltage-dependent Ca$\^$2+/ current. In the presence of TTX, the steady-state currents mainly represented outward K$\^$+/ current which looked like the delayed rectifier K$\^$+/ current. In addition, the membrane currents produced by agonist of excitatory amino acid (EAA) receptor and the endogenous transmitter candidate L-glutamate were recorded in isolated whole-cell voltage clamped neurons as well as responses to inhibitory amino acids (${\gamma}$-amino butyric acid, glycine). Drugs were applied by a method that allows complete exchange of the solution within 1 sec; an infinite number of solutions can be applied to a single cell.

• The Korean Journal of Pain
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• 제35권4호
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• pp.433-439
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• 2022

Background: Repeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH). Methods: [D-Ala², N-Me-Phe⁴, Gly⁵-ol]-enkephalin (DAMGO), a selective µ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum. To determine whether post- or pretreatments with spinal orexin A, dynorphin A, and anti-dynorphin A were effective in OIH, the drugs were injected through an intrathecal catheter whose tip was positioned dorsally at the L3 segment of the spinal cord (5 ㎍ for all). Mechanical hypersensitivity was assessed using von Frey monofilaments. Results: Repeated intradermal injections of DAMGO resulted in mechanical hypersensitivity in rats, lasting more than 8 days. Although the first intrathecal treatment of orexin A on the 6th day after DAMGO exposure did not show any significant effect on the mechanical threshold, the second (on the 8th day) significantly attenuated the DAMGO-induced mechanical hypersensitivity, which disappeared when the type 1 orexin receptor (OX1R) was blocked. However, intrathecal administration of dynorphin or an anti-dynorphin antibody (dynorphin antagonists) had no effect on DAMGO-induced hypersensitivity. Lastly, pretreatment with orexin A, dynorphin, or anti-dynorphin did not prevent DAMGO-induced mechanical hypersensitivity. Conclusions: Spinal orexin A attenuates mechanical hyperalgesia induced by repetitive intradermal injections of DAMGO through OX1R. These data suggest that OIH can be potentially treated by activating the orexin A-OX1R pathway in the spinal dorsal horn.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.237-244
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• 1999

Magnesium ion is known to selectively block the N-methyl-D-aspartate (NMDA)-induced responses and to have anticonvulsive action, neuroprotective effect and antinociceptive action in the behavioral test. In this study, we investigated the effect of $Mg^{2+}$ on the responses of dorsal horn neurons to cutaneous thermal stimulation and graded electrical stimulation of afferent nerves as well as to excitatory amino acids and also elucidated whether the actions of $Ca^{2+}$ and $Mg^{2+}$ are additive or antagonistic. $Mg^{2+}$ suppressed the thermal and C-fiber responses of wide dynamic range (WDR) cell without any effect on the A-fiber responses. When $Mg^{2+}$ was directly applied onto the spinal cord, its inhibitory effect was dependent on the concentration of $Mg^{2+}$ and duration of application. The NMDA- and kainate-induced responses of WDR cell were suppressed by $Mg^{2+}$, the NMDA-induced responses being inhibited more strongly. $Ca^{2+}$ also inhibited the NMDA-induced responses current-dependently. Both inhibitory actions of $Mg^{2+}$ and $Ca^{2+}$ were additive, while $Mg^{2+}$ suppressed the EGTA-induced augmentation of WDR cell responses to NMDA and C-fiber stimulation. Magnesium had dual effects on the spontaneous activities of WDR cell. These experimental findings suggest that $Mg^{2+}$ is implicated in the modulation of pain in the rat spinal cord by inhibiting the responses of WDR cell to noxious stimuli more strongly than innocuous stimuli.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.15-24
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• 2000

Although nociceptive informations are thought to be processed via different neural mechanisms depending on the types of stimuli, sufficient data have not been accumulated yet. We performed a series of experiments to elucidate the possible neural mechanisms as to chemical stimuli such as formalin, capsaicin and ATP. Single unit activity of wide dynamic range (WDR) neurons and high threshold cells were recorded extracellularly from the lumbosacral enlargement of cat spinal cord before and after chemical stimulation to its receptive field (RF). Each chemical substance - formalin $(20{\mu}l,\;4%),$ capsaicin (33 mM) or Mg-ATP (5 mM)- was injected intradermally into the RFs and then the changes in the spontaneous activity, mechanical threshold and responses to the peripheral mechanical stimuli were observed. In many cases, intradermal injection of formalin (5/11) and capsaicin (8/11) resulted in increase of the spontaneous activity with a biphasic pattern, whereas ATP (8/8) only showed initial responses. Time courses of the biphasic pattern, especially the late response, differed between formalin and capsaicin experiments. One hour after injection of each chemical (formalin, capsaicin, or ATP), the responses of the dorsal horn neurons to mechanical stimuli increased at large and the RFs were expended, suggesting development of hypersensitization (formalin 6/10, capsaicin 8/11, and ATP 15/19, respectively). These results are suggested that formalin stimulates peripheral nociceptor, local inflammation and involvement of central sensitization, capsaicin induces central sensitization as well as affects the peripheral C-polymodal nociceptors and neurogenic inflammation, and ATP directly stimulates peripheral nociceptors.