• The Korean Journal of Pain
• /
• 제12권1호
• /
• pp.8-15
• /
• 1999

Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. The present studies, using rats rendered allodynia by loosely constrictive ligation of the common sciatic nerve (Bennett Model) and tight ligation of L5 & L6 spinal nerve (Chung Model), aimed to investigate the changes of metabotrophic glutamate receptor type 5 on the development of tactile allodynia. Male Sprague-Dawley rats (130~200 g) were anesthetized with halothane, the rats were randomly divided into one of these three groups, Group 1 (Sham operation), Group 2 (Bennett model) and Group 3 (Chung model). Seven days after surgical procedure, the animal was reanesthetized and decapitated. The spinal cord was quickly removed and stored at deep freezer for polymerase chain reaction (RT-PCR). In Group 2&3, rats showed that tactile allodynia checked by up-down method with calibrated 8 von Frey hair. The level of gene expression of mGluR5 mRNA was significantly increased in group 2 and 3. These increases was significantly different from sham operation, group 1. It was also showed that the increasing patterns of group 2 and 3 in the gene expression were similar correlation with the results of the threshold for tactile allodynia on von Frey hair test. Even though there were some differences between Bennett model and Chung model, these results suggested that mGluR5 had partly attributed to making a tactile allodynia from these models.

• 한방안이비인후피부과학회지
• /
• 제12권1호
• /
• pp.143-153
• /
• 1999

Background: The vasoreactivity of cerebral artery is currently the subject of increasing interest Transcranial Doppler The purpose of this study was to investigate the analgesic effect of acupuncture in a model of neuropathic pain produced by segmental spinal nerve injury (SSI) in rats. The left L5 and L6 spinal nerves of Sprague-Dawley rats were tightly ligated, and one week later, manual or electro-acupuncture was applied for 30 minutes to the contralateral hindlimb (right side) while the animal was lightly anesthetized with halothane. The mechanical threshold of the paw for ipsilateral (left side) hind limb flinching was determined prior to and 0.5, 1, 2, 4, and 24 hours after termination of acupuncture. The mechanical threshold for flinching was significantly elevated for about 4 hours after manual acupuncture applied to the BL. 60 (Kunlun) point or electro-acupuncture to the BL. 60 and BL. 40 (Weizhong) points. However, manual acupuncture applied to the ST. 36 (Zusanli) point was not effective. Furthermore, systemic naloxone pretreatment had no effect on the acupuncture induced threshold elevation. These data suggests that acupuncture produces a point specific, naloxone independent analgesia in a rat neuropathic pain model. ※ This paper is supported by a grant from the '1996 Jusan Foundation of Wonkwang university.)

• Journal of Yeungnam Medical Science
• /
• 제10권2호
• /
• pp.451-474
• /
• 1993

전신마취, 부위 또는 국소 마취시, 그리고 향부정맥제로 술중 및 중환자실에서 흔히 쓰이는 lidocaine의 용량과, 국소 마취제로 인한 중추 신경계의 독성을 예방 또는 중단시키기 위해 사용되는 diazepam의 전투여시 이로 인한 심혈관계 변화 및 lidocaine의 혈중농도를 관찰, 측정하여 환자의 관리 및 치료에 도움을 얻고자 본 실험을 하였다. Nitrous oxide, halothane으로 마취된 개에서 근육이완제 사용 후 조절호흡하에서 혈중 이산화탄소를 35-45mmHg로 유지하면서 국소 마취체인 lidocaine의 용량을 100 mcg/kg/min, 200 mcg/kg/min, 300 mcg/kg/min로 각각 30분간 지속적 침제하면서, diazepam 전투여 유무에 따른 심혈 역학치의 변화 및 lidocaine의 혈중농도를 측정하고, 억제된 심혈관계에 $CaCl_2$를 투여하여 회복 정도를 관찰하였던 바 아래와 같은 결과를 얻었다. Lidocaine의 지속적 침제량이 증가됨에 따라 심혈관계의 억제가 심하게 나타났으며 평균 동맥압, 심장지수, 일회 박출지수, 좌심실 박출 작업지수, 우심실 박출 작업지수 등은 감소하였고 (p<0.05), 폐동맥 쐐기압, 중심 정맥압, 전신혈관 저항지수 등은 증가하였으나 (p<0.05), 심박동수, 평균 폐동맥압, 폐혈관 저항지수의 변화는 거의 없었다. Lidocaine 100 mcg/kg/min 지속적 침제시는 diazepam을 투여한 II군에서만 평균 동맥압의 의의있는 감소를 보였으며 (p<0.05), lidocaine의 혈중농도는 diazepam투여하지 않은 I군에서는 $3.97{\pm}0.22$에서 $4.48{\pm}0.36$ mcg/ml 범위였고 II 군에서는 $3.70{\pm}0.32$에서 $4.10{\pm}0.22$ mcg/ml범위였다. Lidocaine 200 mcg/kg/min의 지속적 침제시는 I군에서는 평균 동맥압의 감소, 중심정액압의 증가를 나타내었고 (p<0.05), II 군에서는 심장지수의 감소, 폐동백 쐐기압의 증가를 나타내었으며 (p<0.05), lidocaine의 혈중농도는 I군은 $7.50{\pm}0.66$에서 $7.91{\pm}0.77$ mcg/ml, II군에서는 $7.64{\pm}0.79$에서 $8.23{\pm}1.18$ mcg/ml범위로 증가하였다. Lidocaine 300 mcg/kg/min의 지속적 침제시는 I군에서는 평균동맥압, 일회 박출지수, 좌심실 박출 작업지수의 감소가 있었고 (p<0.05), 폐동맥 쐐기압, 중심 정맥압, 전신혈관 저항지수의 증가를 나타내었다 (p<0.05). II군에서는 심장지수, 일회 박출지수, 좌심실 박출 작업지수의 감소가 있었으며 (p<0.05), 폐동맥 쐐기압, 중심 정맥압, 전신혈관 저항지수의 증가를 나타내었다 (p<0.05). 그러나 심박동수, 폐동맥압의 변화는 거의 관찰할 수 없었다. 또한 이때의 혈중 lidocaine의 농도는 I군에서는 $11.30{\pm}2.11$에서 $11.83{\pm}0.59$ mcg/ml범위 로, II군에서는 $12.95{\pm}0.71$에서 $13.79{\pm}0.82$mcg/ml의 범위로 나타내었다. $CaCl_2$ 투여 후는 억제된 심장지수, 일회 박출지수, 전신혈관 저항지수, 폐혈관 저항지수, 좌심실 박출작업지수 및 우심실 박출 작업지수는 회복시켰으나 (p<0.05), 폐동맥 쐐기압, 중심정맥압 등은 오히려 억제시켰다 (p<0.05). 이상에서 자율신경계에 손상이 없으며 산혈증 및 과탄산증이 없는 개에서는 lidocaine의 높은 혈중 농도치에서도 혈역학에 내성이 있었으며, ljdocaine의 중추신경계 독성의 예방 및 치료 목적으로 사용되는 diazepam의 전투여 시에도 추가적인 심혈관계의 억제가 없음을 알 수 있었다. 그러나 자율신경계 이상이 있거나 자율신경계를 억압할 수 있는 약을 사용할 때 또는 산혈증, 과탄산증 및 저산소증이 동반된 환자에 사용할 때에는 세심한 주의가 요할 것으로 생각된다.

• The Korean Journal of Pain
• /
• 제12권2호
• /
• pp.171-176
• /
• 1999

Background: Effect of nitric oxide on the hyperalgesia induced by inflammation is controversial. From our previous experiment, NOS inhibitor, L-NAME given during the induction period decrease mechanical hyperalgesia occured by Freund's complete adjuvant induced inflammation. In addition, we attempted to analyze the effects of L-NAME on mechanical hyperalgesia after the development of inflammation by Freund's complete adjuvant in rat paw. Methods: Male Sprague Dawley rats were divided into four groups; control (normal saline), and three different doses of L-NAME (0.1 mg, 1 mg, 10 mg). Inflammation was induced in rats by injecting 0.15 ml of Freund's complete adjuvant (FCA) intraplantarly. Rats showed typical hyperalgesia within twelve hours after injection and maintained this for about one week. Tests were done 2 days after injection of FCA. After the baseline test either L-NAME or saline was injected under light halothane anesthesia. Effect of L-NAME on hyperalgesia was assessed by measuring mechanical hyperalgesia at 15, 30, 60, 90, 120 minutes. Same experients were repeated on normal rats. Results: When injected at the site of inflammation, L-NAME caused dose dependent decrease in mechanical hyperalgesia. However, normal rats also showed increased mechanical threshold after L- NAME injection. Conclusions: Although L-NAME reduces FCA induced mechanical hyperalgesia, this result may solely be due to inhibition of nitric oxide production and need to be further determined.

• The Korean Journal of Pain
• /
• 제13권1호
• /
• pp.8-18
• /
• 2000

Background: Intraperitoneal (IP) and intrathecal (IT) administration of $\alpha$-amino-3-hydroxy-5-methyl-4-isoxazole-propionic (AMPA) and kainate (KA) receptor antagonist attenuate hyperalgesia in various models of persistent pain. The purpose of this study was to assess the effects of IP and IT LY293558, a novel AMPA/KA receptor antagonist on mechanical hyperalgesia after incision. Methods: Sprague-Dawley rats were anesthetized with halothane and underwent plantar incision. Two hours later, responses to mechanical stimuli were assessed using the response frequency to a nonpunctate mechanical stimulus and withdrawal threshold to calibrated von Frey filaments. One group of rats received vehicle, 5 or 10 mg/kg of LY293558 IP. In the other group, vehicle, 0.2, 0.5 or 2 nmol of LY293558 was administered IT. Ataxia and motor function were also evaluated. Results: Hyperalgesia was persistent in both the vehicle and 5 mg/kg group. IP administration of 10 mg/kg of LY293558 increased withdrawal threshold at 30 and 60 min after incision; deficits in rotorod performance were observed at 30, 60, 90 and 150 min. IT administration of 0.5 nmol of LY293558 increased the median withdrawal threshold at 30 and 60 min. Motor function was only impaired at 30 min. IT administration of 2 nmol produced hemiparesis. Again, inhibition of pain behaviors outlasted the effects on motor function. Conclusions: These data further suggest AMPA/KA receptors are important for the maintenance of pain behaviors caused by incisions. IT administration of LY293558 was more effective than systemic administration and reducing pain behaviors caused by a surgical incision.

• The Korean Journal of Pain
• /
• 제13권2호
• /
• pp.137-142
• /
• 2000

Background: Systemic or intrathecal administration of gabapentin has been shown to reverse various pain states. However, until now, the effect of intracerebroventricular (ICV) gabapentin to noxious stimuli has not been reported. The authors' aim of this study was to determine the effect of ICV gabapentin on the inflammatory nociceptive model, formalin test, in rats. Methods: ICV catheters were implanted under halothane anesthesia. For the nociceptive test, $50{\mu}l$ of 5% formalin was subcutaneously injected into the hindpaw. The effect of ICV gabapentin, administered 10 min before formalin injection, were examined on flinching, mean arterial pressure and heart rate evoked by a injection of formalin. Results: Injection of formalin into the paw resulted in a biphasic flinching and cardiovascular response. ICV gabapentin produced a dose-dependent suppression of the flinching and mean arterial pressure response during phase 1. In contrast, in phase 2, ICV gabapentin did not attenuate the pain behavior. ICV gabapentin did not affect on the baseline mean arterial pressure and heart rate. Conclusions: ICV gbapentin was effective for the acute noxious stimulus but it had no effect on the facilitated states induced by tissue injury.

• The Korean Journal of Physiology and Pharmacology
• /
• 제10권4호
• /
• pp.167-172
• /
• 2006

In the present study, we developed a simple method to predict the neuronal cell death in the mouse hippocampus and striatum following transient global forebrain ischemia by evaluating both cerebral blood flow and the plasticity of the posterior communicating artery (PcomA). Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery (BCCAO) for 30 min. The regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry. The plasticity of PcomA was visualized by intravascular perfusion of India ink solution. When animals had the residual cortical microperfusion less than 15% as well as the smaller PcomA whose diameter was less than one third compared with that of basilar artery, neuronal damage in the hippocampal subfields including CA1, CA2, and CA4, and in the striatum was consistently observed. Especially, when mice met these two criteria, marked neuronal damage was observed in CA2 subfield of the hippocampus. In contrast, after transient BCCAO, neuronal damage was consistently produced in the striatum, dependent more on the degree of rCBF reduction than on the plasticity of PcomA. The present study provided simple and highly reproducible criteria to induce the neuronal cell death in the vulnerable mice brain areas including the hippocampus and striatum after transient global forebrain ischemia.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권2호
• /
• pp.185-192
• /
• 2016

Ampicillin, a ${\beta}$-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G significantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.

• International Journal of Oral Biology
• /
• 제32권2호
• /
• pp.59-65
• /
• 2007

It has been well known that excitatory amino acids, primarily glutamate, are involved in the transmission of nociception in pathological and physiological conditions in the spinal and brainstem level. Recently, peripheral glutamate also play a critical role in the peripheral nociceptive transmissions. The present study investigated the role of N-methyl-D-aspartic acid (NMDA) or non-NMDA ionotropic glutamate receptors in formalin-induced TMJ pain. Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Intra-articular injection was performed under halothane anesthesia. Under anesthesia, AP-7 (10, $100\;{\mu}M$, $1\;mM/20\;{\mu}L$), a NMDA receptor antagonist, or CNQX disodium salt (0.5, 5, 50, $500\;{\mu}M/20\;{\mu}L$), a non-NMDA receptor antagonist, were administered intra-articularly 10 min prior to the application of 5% formalin. For each animal, the number of behavioral responses, such as rubbing and/or scratching the TMJ region, was recorded for nine successive 5-min intervals. Intra-articular pretreatment with 1 mM of AP-7 or $50\;{\mu}M$ CNQX significantly decreased the formalin-induced scratching behavioral responses during the second phase. Intra-articular pretreatment with $500\;{\mu}M$ of CNQX significantly decreased the formalin-induced scratching behavior during both the first and the second phase. These results indicate that the intra-articular administration of NMDA or non-NMDA receptor antagonists inhibit formalin-induced TMJ nociception, and peripheral ionotropic glutamate receptors may play an important role in the TMJ nociception.

• 감성과학
• /
• 제8권2호
• /
• pp.155-160
• /
• 2005

본 연구는 관절통 모델에서 웅담 우황과 웅담 우황 사향의 약침액의 효과를 검사하기 위해 수행되었다. 할로탄 마취하에서 관절통은 수컷 쥐의 관절강내에 $2\%$ carrageenan을 주입하여 유발시켰다. 운동자극에 대한 감각신경의 반응은 약침을 시술하기 전과 후에 기록하였다. 경혈에 주입한 약침은 유해한 운동 자극에 대한 신경의 반응을 억제시켰다 족삼리에 시술한 약침은 합곡에 비해 유해한 자극에 대한 관절 감각신경의 반응을 더 많이 억제시켰다. 이러한 결과는 웅담 우황과 웅담 우황 사향의약침이 관절통을 완화하는 데 효과적인 치료법을 제공할 수 있다는 것을 시사한다.