• Advances in Traditional Medicine
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• v.7 no.5
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• pp.549-555
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• 2008

Bupleuri radix (Umbelliferae), the dried root of Bupleurum Chinense DC, has been clinically used to mitigate pain sensation. The descending pain control system consists of three major components, and modulation of pain in the periaqueductal gray is the most extensively studied descending pain control system. However, the relation of Bupleuri radix on the descending pain control system has not been clarified. In the present study, modulation of the aqueous extract of Bupleuri radix on glycine-induced ion current in the acutely dissociated periaqueductal gray neurons was investigated by using nystatin-perforated patch-clamp technique under voltage-clamp condition. In the present results, the glycine-induced ion current was significantly suppressed by 0.1 mg/ml Bupleuri radix, while treatment with $10^{-5}\;M$ naltrexone, opioid receptor antagonist, alleviated Bupleuri radix-induced inhibition on glycine-induced ion current. The present study showed that the aqueous extract of Bupleuri radix may activate descending pain control system through inhibition on glycine-induced ion current in the periaqueductal gray neurons and this effect is mediated by opioid receptors.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.55-71
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• 2006

Objectives : The present study was investigated the effect and pathway of heterotopic electroacupuncture (EA) on pain induced by formalin in rats. Methods : Acupoints in the right forepaws, $HT_7$ and $PC_7$, were stimulated with 3 mA, 2 ms, and 10 Hz before subcutaneously formalin injection (5%, $50{\mu}l$) to the left hind paw. Moreover, it was investigated whether the dorsolateral funiculus (DLF), as known to the descending inhibition, mediates analgesia of the heterotopic EA, and an administration of naltrexone blocks the effect of EA. Results : In the immunohistochemistry of cFos-like protein (cFL), there were inhibitory effects of EA on the increased expression of cFL in the lumbar spinal dorsal horn neurons following formalin injection. Especially, EA inhibited the expression of cFL on the superficial laminae than that on the deep laminae at 1 hr after, but that on the deep laminae than that on the superficial laminae at 2 hr after. Also, EA suppressed the increased expression of nitric oxide (NO) and neuronal nitric oxide synthase (nNOS) in the lumbosacral spinal cord after formalin injection, but not Sham-EA. Suppressed expressions of cFL, NO and nNOS in the spinal cord were eliminated after transection of the ipsilateral DLF at $T_{10}{\sim}T_{11}$ levels. However, pretreatment of naltrexone could not prevent the suppressive expressions of cFL, NO and nNOS at the spinal cord. Conclusions : These results suggest that the analgesia of heterotopic EA may be modulated through the DLF constituting the descending inhibition.

• Korean Journal of Acupuncture
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• v.26 no.2
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• pp.91-108
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• 2009

Objectives: Single colorectal instillation of trinitrobenzenesulphonic acid (TNBS) causes a dose-dependent increase of visceral motor response (VMR) and severity of inflammation. In this study we compared the effects of electroacupuncture in the different acupoints in the acute colitis induced by TNBS intracolonic injection in rats. Methods: In Male Sprague-Dawley rats, weighing $250{\sim}400g$, a single colorectal administration of TNBS 5mg/kg and 50% ethanol under isoflurane anaesthesia after an overnight fast. Electrodes for electromyography (EMG) recording were stitched into the external oblique musculature under general anesthesia. Acupoints of LI4, ST25, or ST36 were stimulated by electroacupuncture, respectively. The balloon was inserted intra-anally and visceral motor response (VMR) to colorectal distensioin (CRD) was quantified with an EMG recording system. Results: At an observation of the visceral hyperalgesia in the day-time series, the visceromotor response increased significantly 3 days after TNBS intra-rectalcolonic injection in rats. Electroacupuncture on either ST25 or ST36 suppressed the visceromotor response to colorectal distension, but not LI4, at 3 days after TNBS injection. Pretreatment of naltrexone (10 mg/kg, i.p.), opioids antagonist, inhibited the VMR suppress of 10Hz EA to ST36 but not phentolamine (5 mg/kg, i.p.). Pretreatment of either naltrexone or phentolamine inhibited effects of 10Hz EA to ST25. Conclusions: Data show that EA at either ST25 or ST36 potently inhibits hypersensitivity of colorectum after TNBS induced colitis and is differently mediated through the endogenous opioid system and adrenergic system.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.361-382
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• 2022

The third opium war may have already started, not only due to illicit opioid trafficking from the Golden Crescent and Golden Triangle on the international front but also through indiscriminate opioid prescription and opioid diversion at home. Opioid use disorder (OUD), among unintentional injuries, has become one of the top 4 causes of death in the United States (U.S.). An OUD is defined as a problematic pattern of opioid use resulting in clinically significant impairment or distress, consisting of 2 or more of 11 problems within 1 year, as described by the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Observation of aberrant behaviors of OUD is also helpful for overworked clinicians. For the prevention of OUD, the Opioid Risk Tool and the Current Opioid Misuse Measure are appropriate screening tests before and during opioid administration, respectively. Treatment of OUD consists of 3 opioid-based U.S. Food and Drug Administration-approved medications, including methadone, buprenorphine, and naltrexone, and non-opioid-based symptomatic medications for reducing opioid withdrawal syndromes, such as α₂ agonists, β-blockers, antidiarrheals, antiemetics, non-steroidal anti-inflammatory drugs, and benzodiazepines. There are at least 6 recommendable guidelines and essential terms related to OUD. Opioid stewardship programs are now critical to promoting appropriate use of opioid medications, improving patient outcomes, and reducing misuse of opioids, influenced by the successful implementation of antimicrobial stewardship programs. Despite the lack of previous motivation, now is the critical time for trying to reduce the risk of OUD.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.34-45
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• 1998

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical, neurophysiological, neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing neurons are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide- receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone, a potent ${\mu}$-receptor antagonist, has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.

• The Korean Journal of Medicine
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• v.93 no.6
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• pp.501-508
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• 2018

Obesity is a chronic disorder that is a significant risk factor for diabetes, cardiovascular diseases, malignancy, and other chronic diseases. Lifestyle modifications form the basis of most treatments for obesity, but it has become clear that such modifications alone are not enough for many obese patients. When a behavioral approach is insufficient, pharmacological treatment may be recommended. In recent years, the US Food and Drug Administration (FDA) has withdrawn several therapeutic options for obesity due to their side effects, but has approved four novel anti-obesity agents. Until recently, orlistat was the only drug approved for the management of long-term obesity, but the US FDA approved the novel anti-obesity drugs lorcaserin and phentermine/topiramate in 2012, and naltrexone/bupropion and liraglutide in 2014. The present review discusses the different pharmacotherapeutic options for the treatment of obesity.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.117.1-117.1
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• 2003

Colchicine is a drug well known for its use in the therapy of acute attacks of gouty arthritis. Two death caused by oral ingestion of colchicine was reported. Two persons were all women. The one was 34 years old woman and with his boyfriend in a inn and the other was a housewife. The first one was a alcoholic but his boyfriend was afflicted with gout. So her boy friend carried over about 60 tablets of colchicine, 4 tablets of naltrexone and 22 tablets of fluoxetine. After her death there were remained colchicine, 2 tabs, naltraxone 4 tabs and fluoxetine 22 tabs. (omitted)

• Journal of Pharmacopuncture
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• v.13 no.3
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• pp.47-62
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• 2010

Objectives: Colitis is an inflammatory bowel disease characterized by colonic mucosal inflammation and chronic relapsing events represents. The purpose of this study is to evaluate effects of pharmacopuncture of anti-inflammatory herbal compound (AiC) applied to the different acupoints in the acute colitis induced by trinitrobenzenesulphonic acid (TNBS) intracolonic injection in rats. Methods: In Male Sprague - Dawley rats, weighing 250~400g, TNBS (5 mg/kg) was infused intrarectally through a silicon rubber catheter into the anus under isoflurane anaesthesia. Acupoints of LI4 (Hapkok), ST25 (Cheonchu), ST36 (Joksamni), and BL25 (Daejangsu) were intramuscularly injected by AiC, respectively (injection volume & times: 0.2 ml / acupoint, twice times on the 2nd & 3rd day). Expressions of cFos protein in the periaqueductal gray (PAG), locus coeruleus (LC), nucleus of solitary tract (Sol), and the 6th lumbar spinal cord (L6 s.c.) were observed at 24 hr after TNBS induced colitis by immunohistochemistry. Results: The expression of c-Fos protein in the L6 s.c., Sol, LC and PAG increased 24 hr after TNBS injection into colorectum as compared to normal and 50% ethanol treated group. AiC to LI4 inhibited the expression of c-Fos protein in Sol and PAG but not L6 s.c. and LC. AiC to ST36 showed significant inhibition the c-Fos expression in L6 s.c., Sol and PAG. AiC to ST25 only showed the effects in L6 s.c. and PAG. AiC to BL25 inhibited significantly the expression of c-Fos protein all over the areas. To investigate whether or not endogenous opioids are involved, intrathecal injection of naltrexone (30ug/30ul) was applied before the 2nd pharmacopuncture treatment 24 hr after TNBS-induced colitis in rat. Naltrexone reversed the inhibition of c-Fos protein expression in the spinal cord and brainstem. Conclusions: These data show that pharmacopuncture of Aic potently inhibits signal pathways ascending hypersensitivity of colorectum after TNBS induced colitis and depends on the endogenous opioids according to acupoints.

• Korean Journal of Acupuncture
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• v.30 no.4
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• pp.220-229
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• 2013

Objectives : Electroacupuncture(EA) has been used effectively in producing analgesia on ankle sprain pain of humans and animals. Currently to examine the underlying mechanisms of the EA-induced analgesia, the effects of EA on weight-bearing forces(WBR) were examined at ankle sprain classified as grade 3 in rats. Methods : The severe ankle sprain classified as grade 3 was induced surgically by ankle ligament injury in the Sprague-Dawley rats. WBR of the affected foot were examined to evaluate effects and mechanism of EA(2 Hz, 1 ms pulse width, 2 mA intensity, for 15 min) which was applied to either SI6, GB34, or GB39 acupoints. The rats were pretreated with naltrexone(10 mg/kg, i.p.) as an opioid receptor antagonist or phentolamine(5 mg/kg, i.p) as an ${\alpha}$-adrenoceptor antagonist at 30 min before EA. Results : The daily repeat EA at either SI6, GB34, or GB39 showed significant analgesic effects on the severe ankle sprain. Particularly, daily EA at GB34 showed more potent analgesic effect than the others. In addition, the naltrexone pretreatment completely blocked the analgesic effect of EA at GB34, indicating the involvement of the endogenous opioid system in mediating the effect of EA at GB34. However, the phentolamine pretreament blocked analgesic effects of EA at either SI6 or GB39, indicating the involvement of ${\alpha}$-adrenoceptors in mediating the effect of EA at either SI6 or GB39. Conclusions : These data suggest that EA-induced analgesia on ankle sprain pain is mediated through either endogenous opioids or ${\alpha}$-adrenoceptors dependant on acupoint specific pattern.

• Korean Journal of Acupuncture
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• v.26 no.4
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• pp.195-209
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• 2009

Objectives : Transient inflammation has been demonstrated to alter visceral sensory function in animal models and acute mucosal inflammation may precede the manifestation of visceral hyperalgesia. Thus in this study we compared effects of herbal acupuncture of Nidus Vespae (NV) applied to the different acupoints in the acute colitis induced by trinitrobenzenesulphonic acid (TNBS) intracolonic injection in rats. Methods : In Male Sprague-Dawley rats, weighing 250 ~ 400 g, TNBS (5 mg/kg) was infused intrarectally through a silicon rubber catheter into the anus under isoflurane anaesthesia. Under general anesthesia, acupoints of LI4 (Hapkok), SI25 (Cheonchu), ST36 (Joksamni), BL25 (Daejangsu) were intramuscularly injected by NV. Expressions of cFos protein in the periaqueductal gray (PAG), locus coeruleus (LC), nucleus of solitary tract (Sol), and the 6th lumbar spinal cord (L6 s.c.) were observed at 24 hrs after TNBS induced colitis by immunohistochemistry. Results : The expression of c-Fos protein in L6 s.c., Sol, LC and PAG increased 24 hrs after TNBS injection into colorectum as compared to normal group. NV herbal acupuncture also inhibited the expression of c-Fos protein in Sol but not L6 s.c., LC, and PAG. NV to ST36 inhibited significantly the c-Fos expression in Sol and PAG. NV to ST25 inhibited the c-Fos protein expression all over the observation area. NV to BL25 showed the inhibitory effects in the areas except LC. Whether or not a role of endogenous opioids, intrathecal injection of naltrexone (30 ug / 30 ul) was applied before the 2nd herbal acupuncture treatment 24 hrs after TNBS-induced colitis in rat. Naltrexone reversed the inhibition of c-Fos protein expression in the spinal cord and brainstem under different conditions such as type of herbal acupuncture compound and choice of acupoint. Conclusions : In summary, these data show that herbal acupuncture of NV inhibits signal pathways such as spinal cord and brain stem ascending hypersensitivity of colorectum after TNBS induced colitis. This effect may be mediated by acupoints through the endogenous opioid system involving the pain modulation.