• The Korean Journal of Pain
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• v.32 no.2
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• pp.87-96
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• 2019

Background: This study was performed in order to examine the effect of intrathecal sec-O-glucosylhamaudol (SOG), an extract from the root of the Peucedanum japonicum Thunb., on incisional pain in a rat model. Methods: The intrathecal catheter was inserted in male Sprague-Dawley rats (n = 55). The postoperative pain model was made and paw withdrawal thresholds (PWTs) were evaluated. Rats were randomly treated with a vehicle (70% dimethyl sulfoxide) and SOG ($10{\mu}g$, $30{\mu}g$, $100{\mu}g$, and $300{\mu}g$) intrathecally, and PWT was observed for four hours. Dose-responsiveness and ED50 values were calculated. Naloxone was administered 10 min prior to treatment of SOG $300{\mu}g$ in order to assess the involvement of SOG with an opioid receptor. The protein levels of the ${\delta}$-opioid receptor, ${\kappa}$-opioid receptor, and ${\mu}$-opioid receptor (MOR) were analyzed by Western blotting of the spinal cord. Results: Intrathecal SOG significantly increased PWT in a dose-dependent manner. Maximum effects were achieved at a dose of $300{\mu}g$ at 60 min after SOG administration, and the maximal possible effect was 85.35% at that time. The medial effective dose of intrathecal SOG was $191.3{\mu}g$ (95% confidence interval, 102.3-357.8). The antinociceptive effects of SOG ($300{\mu}g$) were significantly reverted until 60 min by naloxone. The protein levels of MOR were decreased by administration of SOG. Conclusions: Intrathecal SOG showed a significant antinociceptive effect on the postoperative pain model and reverted by naloxone. The expression of MOR were changed by SOG. The effects of SOG seem to involve the MOR.

• The Korean Journal of Pain
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• v.19 no.1
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• pp.33-44
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• 2006

Background: Peripheral nerve injury leads to neuropathic pain, including mechanical hyperalgesia (MH). Nerve discharges produced by an injury to the primary afferents cause the release of glutamate from both central and peripheral terminals. While the role of centrally released glutamate in MH has been well studied, relatively little is known about its peripheral role. This study was carried out to determine if the peripherally conducting nerve impulses and peripheral glutamate receptors contribute to the generation of neuropathic pain. Methods: Rats that had previously received a left L5 dorsal rhizotomy were subjected to a spinal nerve lesion (SNL) or brief electrical stimulation (ES, 4 Hz pulses for 5 min) of the left L5 spinal nerve. The paw withdrawal threshold (PWT) to von Frey filaments was measured. The effects of an intraplantar (i.pl.) injection of a glutamate receptor (GluR) antagonist or agonist on the changes in the SNL- or ES-produced PWT was investigated. Results: SNL produced MH, as evidenced by decrease in the PWT, which lasted for more than 42 days. ES also produced MH lasting for 7 days. MK-801 (NMDAR antagonist), DL-AP3 (group-I mGluR antagonist), and APDC (group-II mGluR agonist) delayed the onset of MH when an i.pl. injection was given before SNL. The same application blocked the onset of ES-induced MH. NBQX (AMPA receptor antagonist) had no effect on either the SNL- or ES-induced onset of MH. When drugs were given after SNL or ES, MK-801 reversed the MH, whereas NBQX, DL-AP3, and APDC had no effect. Conclusions: Peripherally conducting impulses play an important role in the generation of neuropathic pain, which is mediated by the peripheral glutamate receptors.

• Journal of Oral Medicine and Pain
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• v.47 no.3
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• pp.126-134
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• 2022

Purpose: This study aimed to propose an efficient treatment approach for infection with different candida species. Methods: Fifty-three patients who presented with a chief complaint of oral mucosal pain and exhibited positive candida culture findings were divided into two groups (Candida albicans and non-albicans). Pain, mucosal manifestations, salivary flow rates, durations of disease and treatment, and responses to treatment (nystatin and clonazepam) were investigated in both groups. Results: Patients in the C. albicans group exhibited more prominent clinical characteristics (erythematous lesions, tongue coatings, and hyperalgesia) than those in the non-albicans group. In total, 70% of patients in the non-albicans group showed no abnormalities in the oral mucosa. Patients in the C. albicans group showed increased resistance to nystatin treatment compared to those in the non-albicans group, especially with longer disease durations. The patients resistant to nystatin treatment showed positive responses to clonazepam. Conclusions: Patients with oral mucosal pain should be tested for the presence of Candida, even in the absence of mucosal abnormalities, especially those infected with non-albicans species. If no response to antifungal therapy is observed, treatment with clonazepam should be initiated, especially in patients infected with C. albicans.

• Journal of Acupuncture Research
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• v.18 no.6
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• pp.215-224
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• 2001

Objcetive : Neuropathic pain sometimes arises from a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It has been well known that acupuncture is effective to the pain control from ancient time in Asia. However, it is not clear whether acupuncture can control neuropathic pain. The aim of the present study is to examine if acupuncture stimulation may be effective to the mechanical allodynia in a rat model of neuropathic pain. Methods : To produce neuropathic pain, under sodium pentobarbital anesthesia, the right superior caudal trunk was resected between the S3 and S4 spinal nerves. After the neuropathic surgery, we examined if the animals exhibited the behavioral signs of mechanical allodynia. The mechanical allodynia was assessed by stimulating the tail with von Frey hair (bending force : 2.0g). three or 6 weeks after the neuropathic surgery, acupuncture stimulation was delivered to Houxi (SI 3) as the following parameters (2HZ frequency, 0.07mA intensity and 3msec duration) for 30 minutes. Results : The stimulation of Houxi (SI 3) acupoint relieved the behavioral signs of mechanical allodynia. Conclusion : Our results suggest that acupuncture can control the mechanical allodynia of neuropathic pain.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.77-90
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• 2006

Objectives : To evaluate the analgesic effect of electroacupuncture on Choksamni (ST36) in the collagen-induced arthritis rats and investigate the role played by serotonergic receptor subtypes $(5-HT_{1A},\;5-HT_{1B},\;5-HT_4)$ in the antinociceptive effect of electroacupuncture in the thermal hyperalgesia test. Methods : Immunization of male Sprague-Dawley rats with bovine type II collagen emulsified in incomplete Freund's adjuvant, followed by booster injection 14 days later induced collagen-induced arthritis (CIA). The thermal hyperalgesia was evaluated weekly with tail flick latency (TFL). In the fourth week after first immunization. EA stimulation (2Hz, 0.07mA, 0.3ms) was delivered into Choksamni for 20 minutes. We measured the analgesic effect of EA with TFL afer intraperitoneal injection of normal saline, WAYl00635, SB216641 and GR125487. Results : TFLs were gradually decreased in CIA as time elapsed after the immunization of arthrogenic collagen and the maximum value was reached from third to fifth week. EA stimulation on ST36 inhibited chronic inflammatory pain induced by CIA. The analgesic effect of EA was inhibited by pretreatment of $5-HT_{1A}$. antagonist (WAYl00635), $5-HT_{1B}$ antagonist (SB216641) and $5-HT_4$ antagonist (GR125487). Conclusion : Electroacupuncture has the analgesic effect on chronic inflammatory pain and its mechanism was mediated by $5-HT_{1A}$, $5-HT_{1B}$ and $5-HT_4$.

• The Korean Journal of Pain
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• v.29 no.3
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• pp.153-157
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• 2016

Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the ${\mu}$-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence.

• The Korean Journal of Pain
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• v.9 no.1
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• pp.39-45
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• 1996

Tachyphylaxis to local anesthetics has shown to be promote longer interanalgesic intervals between injections. Previous study demonstrated thermal hyperalgesia accelerates development of tachyphylaxis to sciatic nerve blockade in rats, while MK-801 prevents development of tachyphylaxis. Dextromethorphan is one of NMDA receptor antagonist similar to MK-801. A hypothesis that dextromethorphan would prevent the development of tachyphylaxis was tested in this study. A catheter was surgically implanted along the sciatic nerve a in rat. After recovery from surgery, the animal received repeated injections of 3% 2-chloroprocaine followed by motor block testing with or without hot-plate testing at $56^{\circ}C$. In other experiments, dextromethorphan was administrered by intraperiotneal injection prior to an injection of local anesthetic therough the implanted catheter. Sensory and motor testing was then carried out. Rats injected with 2-chloroprocaine and subjected to hot-plate testing, developed tachyphylaxis to motor and sensory blockade. However, animals pretreated with dextromethorphan did not develop tachyphylaxis over series of three injections. Dextromethorphan seems to prevent development of tachyphylaxis to sciatic nerve blockade in this rat model. Dextromethorphan, one of N-Methyl-D-aspartate receptor antagonist, can be applied to prolong the effect of local anesthetic.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.150-157
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• 1997

Capsaicin cream has been used to attenuate the pain associated with diabetic neuropathy, rheum-atoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, local irritation, limits the use of it and there is still a need for a new analgesic devoid of this side effect. This study was conducted to compare the local irritant effect of DA-5018, a new capsaicin derivative, with that of capsaicin in various animal models and human beings. Capsaicin, applied topically to the mouse ear, produced dose-dependent increase of ear volume and the frequency of ear scratching behavior in mice. Neither ear volume nor scratching behavior was affected by DA-5018. In eye wiping test of rat, DA-5018 was 10 times less irritant than capsaicin. Capsaicin administered intradermally into the rat paw elicited paw lick/lift response with a potency which was three times that of DA-5018. Zostrix-HP (0.075% capsaicin cream), but not DA-50180.3% cream, increased ear volume of rat and induced thermal hyperalgesia in normal and carrageenan inflamed paws. Six day-treatment of Zostrix-HP failed to develop tolerance against this thermal hyperalgesia. In human beings, Zostrix-HP produced burning sensation and itching in more than 90% of volunteers involved and its maximum irritant effect was significantly higher than that of DA-5018 cream. These results suggest that local irritation and burning sensation produced by DA-5018 is much less than capsaicin.

• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.88-95
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• 1986

Clinically, subhypnotic doses of barbiturates have been known to elicit hyperalgesia. In this experiment, effect of acute or chronic phenobarital treatment on the response to pain in rat was reevaluated by hot-plate method. To elucidate its mechanism, changes of ${\beta}-endorphin$ contents and [3H]-morphine binding of the rat midbrain as well as functional opiate receptor in vas deferens were also measured. Intraperitoneal injection of sub anesthetic dose phenobarbital induced initial hyperalgesia followed by successive analgesia, while chronic phenobarbital-treatment decreased reactivity to pain. Naloxone (10mg/kg, i.p.) markedly shortened hot plate latency period, and significantly inhibited the analgesic action of phenobarbital. Single dose of phenobarbital did not affect ${\beta}-endorphin$ contents and [3H]-morphine binding in rat mid brain, but in the chronic phenobarbital-treated groups, ${\beta}-endorphin$ contents was increased, while Bmax of opiate receptor binding was decreased. Moreover, very significant correlations among responses to pain, changes of ${\beta}-endorphin$ contents and opiate receptor binding were observed. However, Kd values of opiate receptor bindings were not changed in all preparations. In the chronic phenobarbital-treated vas deferens preparations, ID50 of morphine was increased witb concomittant decrease of maximum effect. But $pA_2 $, value for naloxone was not changed. From these results, it is suggested that phenobarbital can produce analgesia due to changes of ${\beta}-endorphin$ contents as well as functional opiate receptors by receptor regulation.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.394-404
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• 2021

Background: We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). Methods: This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. Results: A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. Conclusions: Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A_2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.