• Journal of the Korean Applied Science and Technology
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• v.19 no.4
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• pp.281-290
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• 2002

Dermorphin is a hepta peptide(H-Tyr-DAla-Phe-Gly-Tyr-Pro-Ser-$NH_{2}$)with exceptionally potent and long-lasting peripheral and central activity. Dermorphin analogues, dermorphionyl(DMP)-Lys-$NH_{2}$ and DMP-Lys-Lys-$NH_{2}$ have been prepared in order to examine the effect of opiod activity. Dermorphin analogues were synthesized by the solid phase method. The crude peptide was purified by gel filter on a Sephadex LH-20, characterized with HPLC and amino acid analyzer. Analgesic potency was estimated by writhing syndrome method and Randall-Selitto method. As a result, dermorphin analogues have lower potency than that of morphine.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.173-182
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• 2018

Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by $d(CH_2)_5[Tyr(Me)^2,Dab^5]$ AVP, a vasopressin-1a (V1a) receptor antagonist, but not by $desGly-NH_2-d(CH_2)_5[D-Tyr^2,Thr^4]OVT$, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.

• Clinical Pain
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• v.18 no.1
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• pp.36-39
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• 2019

Chronic postoperative inguinal pain (CPIP) is a major complication after inguinal herniorrhaphy. We report the treatment of CPIP using ultrasonography-combined with nerve stimulator for injection of the genitofemoral nerve (GFN). A 59-year-old man underwent laparoscopic herniorrhaphy and presented with numbness from the inguinal region to the scrotum after operation. In the pain clinic, ultrasonography-guided GFN block and pharmacological treatments had little effect. Six month after operation, patient was referred to the Department of Physical Medicine and Rehabilitation, and ultrasonography-combined with nerve stimulator for GFN injection underwent to enhance the accuracy of neural approach. The induction of scrotal contraction and paresthesia on the GFN distribution was monitored by nerve stimulator and local anesthetic was injected. After the block, pain relief lasted for 6 months without analgesic use. Ultrasonography-combined with nerve stimulator is an effective approach to treat CPIP as it enhances precise localization and injection of small peripheral nerve like GFN.

• The Journal of Korean Medicine
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• v.25 no.3
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• pp.67-77
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• 2004

Objectives : Many studies have reported that acupuncture analgesia was mediated through the activation of peripheral and central opioid receptors. However, there has been little electrophysiological study on the adrenergic mechanism of acupuncture analgesia in chronic inflammatory and neuropathic pain. The present study was undertaken to elucidate the role of adrenoceptors in the production of acupuncture analgesia in the chronic pain model. Methods : In the rat with chronic inflammation and nerve injury, dorsal horn cell (DHC) responses to afferent C fiber stimulation were used as a pain index and changes in electroacupuncture (EA) analgesia were recorded before and after intravenous administration of selective adrenoceptor antagonists. EA stimulations (2Hz, 0.5msec, 3mA) were applied to the contralateral Zusanli point for 30 min. Results : EA stimulation induced long-lasting inhibition of DHC responses in the rat with chronic inflammation and nerve injury. In both models of inflammation and neuropathic pain, α-adrenoceptor antagonist (phentolamine) significantly attenuated an inhibitory effect of EA on DHC responses. Selective α2-adrenoceptor antagonist (yohimbine) also had a similar suppressive action on DHC responses to that of phentolamine. However, β-adrenoceptor antagonist (propranolol) did not have any inhibitory effect on DHC responses in either model of chronic pain. Conclusions : These experimental findings suggest that in rats with chronic pain, EA stimulation with low frequency and high intensity produced an analgesic effect which was mediated through an activation of α2-adrenoceptors.

• Journal of Chest Surgery
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• v.29 no.5
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• pp.477-486
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• 1996

Endogenous analgesic systems are known to be activated by peripheral noxious stimulation as well as arterial carbon dioxide elevation. In the present study, neuronal Activities in the rostral ventrolateral med- ulla were identified and classified in according to their rhythmic activities, and their responses to noxious peripheral nerve stimulations before and after elevating the arterial carbon dioxide partial pressure were investigated Using extracellular recording technic, a total of 53 spontaneously active neurons were recorded from the rostral ventrolateral medulla in u-chloralose anesthetized cats. These were classified as cardiovascular (28), respiratory (16), both cardiovascular and respiratory (2) and noncardiovascular - nonrespiratory (7). - Among the 28 cardiovascular neurons eleven showed increased activities during arterial hypercapnia, thirteen showed decreased responses, and four showed no change. Nine respiratory neurons showed increased responses to arterial hypercapnia, six showed decreased responses and one showed no change. neither of the cardiovascular and respiratory neurons showed significant change in its activity during ar- terial hypercapnia, however, four of the noncardiovascular - nonrespiratory neurons exhibited decreased their activities in response to arterial hypercapnia while two exhibited increased activities. Arterial hypercapnia increased the responses of cardiovascular neurons to peripheral nerve stimulation with C-inteniity, while not changing the responses to Ak_stimulation significantly . From the above results it was conclllded that during arterial hypercapnia, some cardiovascular neurons and respiratory neurons have increased activities as well as increased reponses to C-Hber stimulation.

• Journal of Food Hygiene and Safety
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• v.9 no.3
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• pp.163-168
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• 1994

In the present study we investigated the peripheral function of capsaicin and KR-25018, a newly synthesized capsaicin derivative, which was demonstrated to have a potent analgesic activity through different mechanism from morphine and nonsteroidal antiinflammatory drugs. Capsaicin (10-8~10-5 M) and KR-25018 (10-8~10-5 M) produced concentration-dependent contractions of the isolated guinea pig bronchi. There were no significant differences in the maximum response and the EC50 values (EC50: 0.137$\pm$0.025 $\mu$M and 0.097$\pm$0.031 $\mu$M for capsaicin and KR-25018, respectively, P>0.05). Phosphoramidon (10 $\mu$M) and indomethacin (10 $\mu$M) had no significant effect on contractile response to the submaximal concentration range of capsaicin and KR-25018 (3$\times$10-9~3$\times$10-7 M). The response to KR-25018, like that to capsaicin, was significantly inhibited by ruthenium red with reduction in the maximum response, which is indicative of non-competitive antagonism. A further common feature of the responses to capsaicin and KR-25018 in the guinea pig bronchi was their sensitivity to capsazepine. Capsazepine caused a rightward parallel shift in concentration-response curves obtained by capsaicin and KR-25018. the pA2 values of capsazepine were 5.90 and 5.99 against capsaicin and KR-25018 response, respectively. In conclusion, KR-25018 and capsaicin exert their contractile effects in the isolated guinea pig bronchial muscle by common mechanisms, probably via the activation of a specific receptor.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.252-252
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• 1996

We Investigated the peripheral excitatory effect of capsaicin and KR-25018, a newly synthesized capsaicin derivative which was demonstrated to have a potent analgesic activity. KR-25018 and capsaicin were found to be both potent efficacious contractors of isolated guinea pig bronchial smooth muscle. KR-25018 was equipotent with capsaicin and [Sar$\^$9/,Met(O$_2$)$\^$11/]-substance P, 10-fold more potent than histamine and 10-fold less potent than (${\beta}$ -Ala$\^$8/)-neurokinin A(4-10), and their -log(M)EC$\_$50/ values were 6.94${\pm}$0.08, 6.86${\pm}$0.05, 6.96${\pm}$0.07, 5.64${\pm}$0.04, 7.96${\pm}$0.02, respectively. Contractile responses to KR-25018 and capsaicin were potentiated by phosphoramidon (1 ${\mu}$M), an inhibitor of neuropeptide-inactivating endopeptidase, but completely abolished in a calcium-free medium. These responses to KR-25018 and capsaicin were unaffected by the NK-1 antagonist CP96345 (1${\mu}$M), partially inhibited by the NK-2 antagonist SR48968 (1 ${\mu}$M) but almost completely abolished by a combination of the antagonists. A vanilloid receptor antagonist capsazepine competitively antagonized the responses to both KR-25018 and capsaicin (pA$_2$: aganst KR-25018, 5.98${\pm}$0.47; against capsaicin, 5.80${\pm}$0.31), and a capsaicin-sensitive cation channel antagonist ruthenium red caused significant reduction in the maximum responses to KR-25018 and capsaicin (pD'$_2$: against KR-25018, 4.61${\pm}$0.33; against capsaicin 4.96${\pm}$0.21). In conclusion, the present results suggest that KR-25018 and cpasaicin act on the same vanilloid receptor inducing the influx of calcium through ruthenium red-sensitive cation channel and produce contractile responses via the release of tachykinins that act on both NK-1 and NK-2 receptor subtypes.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.391-402
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• 2022

Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats. Methods: Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots. Results: The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats. Conclusions: BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.168-175
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• 2023

Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Na_v1.7 or the cardiac sodium channel Na_v1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Na_v1.7 and 0.43 mM for Na_v1.5 at a holding potential of -100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Na_v1.7 and Na_v1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Na_v1.7 and Na_v1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Na_v1.7 or show cardiotoxicity by blocking Na_v1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

• Restorative Dentistry and Endodontics
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• v.17 no.1
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• pp.10-21
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• 1992

The purpose of this study was to investigate the analgesic effect of eugenol, capsaicin and demethoxy-NE. Young adult cats, weighing 2.0 to 3.0kg, were used. Each animal was anesthetized (${\alpha}$-chloralose 60mg per kg body weight) and divided into four groups; control, eugenol, capsaicin and demethoxy-NE group. The anterior digastric muscles were exposed and a pair of electrodes was inserted to record the electromyograms. To expose the pulp, each canine teeth was prepared with a low speed bur under cooling and used for recording anterior digastric muscular EMGs evoked by noxious stimulation of dental pulp. To observe effects on jaw opening reflex, inferior alveolar nerve of both sides were exposed for drug application and wire electrodes were inserted in anterior digstric muscle for recording the EMGs. To observe effects on action potential, saphenous nerves of both sides were exposed and three tissue pools were made from surrounding tissue. The most distal pool was used for applying stimulation, the most proximal one for recording of action potential, and the other one for drug application. One side of inferior alveolar nerve and saphenous nerve were used for eugenol, capsaicin, or demethoxy-NE application, the other side of nerve for control experiments(only vehicle application). Anterior digastric muscular EMGs evoked by noxious stimulation of dental pulp were recorded before drug application, immediate after drug application, at 60 and 120 minutes, and 5 days after drug application. Action potentials were recorded before drug application, immediate after 30 minutes drug application, at 30, 60 and 120 minutes after drug had been washed out. The results were as follows; 1. Eugenol had a continuous blocking effect on the anterior digastric muscular EMGs evoked by noxious pulp stimulation and after 5 days, showed completely blocking effect. 2. After 5 days, demethoxy-NE applied to dental pulp had a considerable blocking effect on the jaw opening retlex evoked by noxious stimulation but capsaicin had no significant effect. 3. After 5 days, eugenol group showed the strongest blocking effect among the all experimental groups on the jaw opening reflex evoked by noxious stimulation of dental pulp and capsaicin group showed the weakest blocking effect. 4. Eugenol had a completely blocking effect on the action potential conductivity of peripheral nerve. Capsaicin and demethoxy-NE had the blocking effect on the action potential conductivity of ${\alpha}$-and C-nerve fibers. 5. Capsaicin, demethoxy-NE and eugenol applied to inferior alveolar nerve surppressed the jaw opening reflex evoked by noxious stimulation of dental pulp.