• Molecules and Cells
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• v.20 no.3
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• pp.315-324
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• 2005

Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.180-186
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• 1999

Eugenol has been reported to reduce odontogenic pain and is known to have a structure similar to capsaicin, a potent stimulant of certain nociceptors. We have hypothesized that the analgesic effect of eugenol may be due, in part, to inhibition of capsaicin-sensitive nociceptors. To test this hypothesis, we evaluate whether eugenol inhibits capsaicin-sensitive release of immunoreactive calcitonin generated peptide(iCGRP) from bovine dental pulp. Freshly extracted bovine incisors were transported to the lab. on ice, Spilitted and pulp tissue was removed. The tissue was chopped into 200${\mu}m$ slices. Dental pulp was superfused(340 ${\mu}l/min$) in vitro with oxygenated Kreb's buffer. Eugenol and vehicle(0.02% 2-hydroxyl-${\beta}$-cyclodextrin) were administered prior to stimulation of pulp with capsaicin and iCGRP was measured by RIA. The results were as follows: 1. Administration of eugenol has no effect on basal release of iCGRP. 2. In the vehicle treated group, capsaicin evoked a 2.5-fold increase over basal iCGRP levels. 3. Administration of eugenol(600 ${\mu}M$) reduced capsaicin evoked release of iCGRP by more than 40%(153.4${\pm}$41.1% vs 258.9${\pm}$21.7%). 4. 2-hydroxylpropyl-${\beta}$-cyclodextrin of less than 0.02% is found to be an effective vehicle to dissolve eugenol without evoking iCGRP release from dental bovine pulp. These data indicate that eugenol inhibits pulpal capsaicin-sensitive fibers and suggest that intracanal medicament of eugenol may relieve pain, in part, by this mechanism.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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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.

• The Transactions of the Korean Institute of Electrical Engineers D
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• v.52 no.9
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• pp.560-567
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• 2003

EMG recordings of the electrical activity of muscle have proved to be a valuable tool in studying muscle function and reflex activity. SP(silent period) is elicited by a electrical stimulation on the chin during isometric contraction of jaw muscle. This paper proposes a model of the inhibitory reflex mechanism of jaw muscle after electrical stimulation. The SPs of jaw muscle after a electrical stimulation to the chin were divided into SP1 and SP2. SP1 is produced by the activation of periodontal receptors. The activation of nociceptors contributes to the SP2. As a result, the EMG signal generated by a proposed a model of inhibitory reflex mechanism is similar to real both EMG signal including SP1 and SP2. The present study have shown differences of SP1 and SP2 induced by inhibitory reflex mechanism.

• The Transactions of the Korean Institute of Electrical Engineers D
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• v.52 no.2
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• pp.112-119
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• 2003

This paper proposes a model of SP(silent period) generation in masseter muscle by means of computer simulation. The model is based on the anatomical and physiological properties of trigeminal nervous system. In determining the SP generation pathway, evoked SPs of masseter muscle after mechanical stimulation to the chin are divided into normal and abnormal group. Normal SP is produced by the activation of mechanoreceptors in periodontal ligament. The activation of nociceptors contributes to the latter part of normal SP, abnormal extended SP is produced. As a result, the EMG signal generated by a proposed SP generation model is similar to both real EMG signal including normal SP and abnormal extended SP with TMJ patients. The result of this study have shown differences of SP generation mechanism between subjects both with and without TMJ dysfunction.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.192.1-192.1
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• 2003

Histamine is found in most tissues of the body and activates polymodal nociceptors via unmyelinated afferent C-fibres. We have demonstrated that bradykinin. acting at B2 bradykinin receptors. excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid in dorsal root ganglion. Histamine is known to the activator of phospholipase A2- arachidonic acid pathway via a G-protein- coupled H1 receptor. (omitted)

• Journal of Medicine and Life Science
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• v.20 no.1
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• pp.1-7
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• 2023

Transient receptor potential ankyrin 1 (TRPA1) receptors are major polymodal nociceptors that generate primary pain responses in the peripheral nerve endings of the dorsal root ganglion neurons. Recently, we reported that the activation of TRPA1 receptors by reactive oxygen species (ROS) signaling, which is triggered by Ca²⁺ influx through T-type Ca²⁺ channels, contributes to prolonged pain responses induced by jellyfish toxin. In this review, we focus on the characteristics of the TRPA1 receptor involved in intracellular signaling as a secondary pain modulator. Unlike other transient receptor potential receptors, TRPA1 receptors can induce membrane depolarization by ROS without exogenous stimuli in peripheral and central sensory neurons. Therefore, it is important to identify the functional characteristics of TRPA1 receptors to understand pain modulation under several pathogenic conditions such as neuropathic pain syndromes and autoimmune diseases, which are mediated by oxidative signaling to cause chronic pain in the sensory system.

• Journal of Acupuncture Research
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• v.33 no.2
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• pp.97-108
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• 2016

Objectives : This study was performed to investigate the analgesic effect of Styrax japonica pharmacopuncture on formalin induced pain in rats and to figure out efficient extraction method. Methods : The subjects were divided into 5 groups ; normal group(treated with normal saline at KI03, and injected normal saline at right hindpaw after 35 minutes), control group(treated with normal saline at KI03, and injected with formalin at right hindpaw after 35 minutes), water group(treated by hot water extraction pharmacopuncture at KI03, and injected with formalin at right hindpaw after 35 minutes), ethanol group(treated with ethanol extraction pharmacopuncture at KI03, and injected with formalin at right hindpaw after 35 minutes), and ultrasound group(treated with ultrasound extraction pharmacacupuncture and injected with fromalin formalin at right hindpaw after 35 minutes). We conducted a formalin test with ultrasonic vocalization( USV), and after the test checked for substance P, Aspartate aminotransferase(AST), and Alanine aminotransferase(ALT) concentration in the blood for each of the groups. Results : There was a significant analgesic effect of Styrax japonica pharmacopuncture in the early phase of the formalin test, and pharmacopuncture made with an ultrasound extracting method was observed to have a better analgesic effect than other extracting methods in early phases. The substance P concentration decreased significantly in the Styrax japonica pharmacopuncture treated group and no difference was found in the AST and ALT concentration of each group. Conclusion : These results demonstrated that Styrax japonica pharmacopuncture had analgesic effects in noxious nociceptors stimulation. Also pharmacopuncture made with an ultrasound extracting method had a better analgesic effect than others.

• The Korean Journal of Pain
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• v.21 no.3
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• pp.187-196
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• 2008

Background: Upregulation of one type of the pro-inflammatory chemokine (CCL2) and its receptor (CCR2) following peripheral nerve injury contributes to the induction of neuropathic pain. Here, we examined whether another type of chemokine (CCL3) is involved in neuropathic pain. Methods: We measured changes in mechanical and thermal sensitivity in the hind paws of naïve rats or rats with an L5 spinal nerve ligation (SNL) after intra-plantar injection of CCL3 or met-RANTES, an antagonist of the CCL3 receptor, CCR1. We also measured CCL3 levels in the sciatic nerve and the hind paw skin as well as CCR1 expression in dorsal root ganglion (DRG) cells from the lumbar spinal segments. Results: Intra-plantar injection of CCL3 into the hind paw of naive rats mimicked L5 SNL-produced hyperalgesia. Intra-plantar injection of met-RANTES into the hind paw of rats with L5 SNL attenuated hyperalgesia. L5 SNL increased CCL3 levels in the sciatic nerve and the hind paw skin on the affected side. The number of CCR1-positive DRG cells in the lumbar segments was not changed following L5 SNL. Conclusions: Partial peripheral nerve injury increases local CCL3 levels along the degenerating axons during Wallerian degeneration. This CCL3 binds to its receptor, CCR1, located on adjacent uninjured afferents, presumably nociceptors, to induce hyperalgesia in the neuropathic pain state.

• The Korean Journal of Pain
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• v.31 no.3
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• pp.174-182
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• 2018

Background: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. Methods: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. Results: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). Conclusions: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.