• The Korean Journal of Physiology and Pharmacology
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• 제9권2호
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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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.

• The Korean Journal of Pain
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• 제13권1호
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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.

• 대한물리치료과학회지
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• 제8권2호
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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.

• 약학회지
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• 제43권3호
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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.

• 약학회지
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• 제43권2호
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• pp.263-273
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• 1999

When glutamate was infected intrathecally, the result is similar to those produced by TPA injected. The involvement of protein kinase C (PKC) in the nociceptive responses in rat dorsal horn neurons of lumbar spinal cord was studied. In test with formalin, a PKC inhibitor (chelerythrine) inhibited dose-dependently the formalin-induced behavior response. Neomycin also inhibited it significantly. But, a PKC activator (12-O-tetradecanoylphorbol-13-ester, TPA) showed reverse effect. When gluatamate was injected intrathecally, we observed the result is smilar to those produced by TPA injection. On the other hand, intrathecal injection of glutamate induced thermal and mechanical hyperalgesia. In Tail-flick test, we examined the involvement of PKC on the glutamate-indeced thermal hyperalgesia. Chelerythrine showed an inhibitory effect and TPA enhanced thermal response. Glutamate decreased the mechanical threshold significantly. A pretreatment of chelerythrine and neomycin inhibited glutamate-induced mechanical hyperalgesia, but the effect of neomycin was not significant. TPA had little effect on the mechanical nociceptive response. These results suggest that the PKC activation through metabotropic receptor at postsynaptic region of spinal cord dorsal horn neurons may influence on the persistent nociception produced by chemical stimulation with formalin, thermal and mechanical hyperalgesia induced by glutamate.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.365-373
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• 1999

Somatostatin (SOM) is one of the major neuropeptides in dorsal root ganglion cells, but its role in spinal nociceptive process has not been well known. In present study we aimed to investigate the effect of SOM on the response of dorsal horn neurons to the various types of peripheral nociceptive stimuli in anesthetized cats. Using carbon-filament microelectrode, the single cell activities of wide dynamic range neurons were recorded from the lumbosacral enlargement after noxious mechanical (squeeze), thermal (radiant heat lamp) and cold (dry ice) stimulation to the receptive field. Sciatic nerve was stimulated electrically to evoke $A\;{\delta}-$ and C-nociceptive responses. SOM analogue, octreotide $(10\;{\mu}g/kg),$ was applied intravenously and the results were compared with those of morphine (2 mg/kg, MOR). Systemic SOM decreased the cellular responses to the noxious heat and the mechanical stimulation, but increased those to the cold stimulation. In the responses to the electric stimuli of sciatic nerve, $A\;{\delta}-nociceptive$ response was increased by SOM, while C-nociceptive response was decreased. On the other hand, MOR inhibited the dorsal horn cell responses to all the noxious stimuli. From the above results, it is concluded that SOM suppresses the transmission of nociceptive heat and mechanical stimuli, especially via C-fiber, while it facilitates those of nociceptive cold stimuli via $A\;{\delta}-fiber$.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.419-425
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• 2018

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of ${\mu}$-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective ${\mu}$-opioid agonist, [$D-Ala^2$, $NMe-Phe^4$, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by $K^+$ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.

• Animal cells and systems
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• 제4권4호
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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.

• 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.