척추손상으로 유도된 백서의 통각과민 반응에서 항신경성장인자의 복강 내 주입에 의한 통증 완화 효과

곽영섭 ( Young Seob Gwak ),배정윤 ( Jung Yoon Bae ),장준호 ( Jun Ho Jang ),윤덕미 ( Duck Mi Yoon ),남택상 ( Taick Sang Nam ),백광세 ( Kwang Se Paik ),임중우 ( Joong Woo Leem ) 대한통증학회 2003 The Korean Journal of Pain Vol.16 No.1

척수손상 후 척수 내 Ionotropic Glutamate 수용기 활성화가 중추 신경병증성 통증 유발에 미치는 영향

곽영섭(Young Seob Gwak),심범(Beom Shim),윤덕미(Duck Mi Yoon),남택상(Taick Sang Nam),백광세(Kwang Se Paik),임중우(Joong Woo Leem) 대한통증학회 2002 The Korean Journal of Pain Vol.15 No.1

N/A Background: Spinal cord injury (SCI) induces the development of central neuropathic pain which is characterized by symptoms such as allodynia, hyperalgesia, and spontaneous pain. However, the underlying mechanism is not fully understood. This study was conducted to see if activation of the glutamatergic system in the spinal dorsal horn is involved in the development of central pain following SCI. Methods: SCI was induced by a hemisection of the spinal cord at T13 in adult, male, Sprague-Dawley rats. Mechanical allodynia was tested by measuring paw withdrawal frequency in response to repeated applications of a von Frey hair to the plantar surface of the hind paw. Single neuronal activity of dorsal horn neurons (L4-L6) was recorded extracellularly using a carbon filament-filled glass microelectrode (2-4 Mℓ). The drugs were intrathecally and topically administrated on the spinal surface for behavioral and electrophysisological study, respectively. Results: After left spinal hemisection at T13, behavioral signs of mechanical allodynia developed on both hind limbs and the responsiveness of spinal dorsal horn neurons increased on both sides of the spinal dorsal horn. Ionotropic glutamate receptor antagonists including MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) suppressed mechanical allodynia and increased responsiveness on both hind paws. Metabotropic glutamate receptor antagonist MCPG, however, had no significant effect. Conclusions: These results indicate that activation of the ionotropic, but not metabotropic, glutamatergic system in the spinal cord plays a key role in the development of central pain following SCI.

신경병증성 통증 모델 쥐에서 뇌간 핵의 전기자극이 후각세포의 기계자극에 대한 반응도에 미치는 영향

임중우,최윤,곽영섭,남택상,백광세,Leem Joong-Woo,Choi Yoon,Gwak Young-Seob,Nam Taik-Sang,Paik Kwang-Se 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.3

The aim of the present study is to examine the brainstem sites where the electrical stimulation produces a suppression of dorsal horn neuron responses of neuropathic rats. An experimental neuropathy was induced by a unilateral ligation of L5-L6 spinal nerves of rats. Ten to 15 days after surgery, the spinal cord was exposed and single-unit recording was made on wide dynamic range (WDR) neurons in the dorsal horn. Neuronal responses to mechanical stimuli applied to somatic receptive fields were examined to see if they were modulated by electrical stimulation of various brainstem sites. Electrical stimulation of periaqueductal gray (PAG), n. raphe magnus (RMg) or n. reticularis gigantocellularis (Gi) significantly suppressed responses of WDR neurons -to both noxious and non-noxious stimuli. Electrical stimulation of other brainstem areas, such as locus coeruleus. (LC) and n. reticularis paragigantocellularis lateralis (LPGi), produced little or no suppression. Microinjection of morphine into PAG, RMg, or Gi also produced a suppression as similar pattern to the case of electrical stimulation, whereas morphine injection into LC or LPGi exerted no effects. The results suggest that PAG, NRM and Gi are the principle brainstem nuclei involved in the descending inhibitory systems responsible for the control of neuropathic pain. These systems are likely activated by endogenous opioids and exert their inhibitory effect by acting on WDR neurons in the spinal cord.

신경병증성 통증모델 쥐에서 피부통각수용체의 민감화

심범(Beom Shim),곽영섭(Young Seob Gwak),임중우(Joong Woo Leem),남택상(Taick Sang Nam),백광세(Kwang Se Paik),윤덕미(Duck Mi Yoon) 대한통증학회 2002 The Korean Journal of Pain Vol.15 No.1

N/A Background: Peripheral nerve injury leads to neuropathic pain. Although it has been accepted that both peripheral and central processes may play a role in the pathophysiology of these sensory abnormalities, the involvement of peripheral mechanisms is often overlooked. The present study was conducted using neuropathic rats to see if cutaneous were sensitized and developed adrenergic sensitivity after peripheral nerve injury. Methods: Single fiber recording thchnique was to record the neural activity of nociceptive fiber in sural or plantar nerves of control rats and of rats that had previously received the L5-L6 spinal nerve ligation (neuropathic rats).Mechancial and heat thresholds of the recorded fibers were determined using von Frey filaments and thermal stimulators, respectively, which were applied to somatic receptive fields. Responses to supranthreshold mechanical and heat stimuli were also studied. The adrenergic sensitivity of nociceptive fibers was investigated by injecting intra-arterially the a_1-adrenergic agonist, phenylephrine. Results: Both mechanical and heat thresholds of nociceptive fibers in neuropathic rats were significantly lowered than those in control rats. In responses to suprathershold stimuli, neuropathic nociceptive heat-suprathreshold response were not significantly different from those of control rats. About 10% of sampled nociceptive fibers in neuropathic rats responded to phenylephrine. Conclusions: The results suggest that nociceptive on the skin supplied by injured nerves are sensitized to both mechanical and heat stimuli, and develop adrenergic sensitivity following peripheral nerve injury. The sensitization and adernergic sensitivity of cutaneous nociceptive may play a role, in part, in the development of neuropathic pain.

신경병증성통증 모델쥐에서 냉자극 유발 통증의 교감신경성 의존도

최병욱(Byung Ock Choi),최윤(Yoon Choi),곽영섭(Young Seob Gwak),남택상(Taick Sang Nam),백광세(Kwang Se Paik),임증우(Joong Woo Leem) 대한통증학회 2000 The Korean Journal of Pain Vol.13 No.2

N/A Background: Peripheral nerve injury sometimes leads to chronic neuropathic pain such as causalgia. A subset of patients with causalgia have a sympathetically maintained pain which is often evoked by cooling stimuli. However, our knowledge on adrenergic receptor types responsible for cold-evoked pain that is sympathetically dependent is lacking. The present study was conducted to investigate subtypes of adrenoceptors involved in mediating cold-evoked pain that developed following peripheral #nerve injury. Methods: Neuropathic surgery was performed by a unilateral ligation of LS and L6 spinal nerves of rats. Behavioral sign of cold-evoked pain was examined for 5 min by measuring cumulative duration of time that the rat lifted its foot off a metal plate held at cold temperature (5℃). Whether cold-evoked pain behavior was affected by antagonists of various subtypes of adrenoceptors, which were administered intraperitoneally before and after the ligation, was investigated. Results: After ligation, duration of foot lifting on the ligated side at cold temperature increased as compared to the pre-operative period. This increase maintained for the entire 40-day test period. Pretreatment with alpha-antagonist phentolamine produced a suppression of cold-evoked pain behavior that was not affected by beta-antagonist propranolol pretreatment. Prazosin, alpha-1 antagonist, suppressed cold-evoked pain behavior when treated either before or after nerve ligation. On the other hand, alpha-2 antagonist yohimbine was without effect on cold-evoked pain behavior whether it was treated before or after the ligation. Conclusions: The results suggest that peripheral nerve injury develops cold-evoked pain that is sympathetically dependent, and that alpha-1 adrenoreceptor plays a critical role for the generation of this type of pain in its initiation as well as maintenance.

쥐의 초음파음성과 마약 중독

전소정 ( So Jeong Jun ),장수찬 ( Su Chan Chang ),곽영섭 ( Young Seob Gwak ),김희영 ( Hee Young Kim ) 대구한의대학교 제한동의학술원 2014 東西醫學 Vol.39 No.3

Objective: In short review, we briefly summarize the relationship between methamphetamine (or amphetamine) and ultrasonic vocalizations (USV s) and how USV s differ depending on the amount of cocaine and amphetamine on rats. Materials and Methods: 1. We reviewed several articles concerning the effects of methamphetamine, cocaine, and amphetamine on rats`` ultrasonic vocalizations. 2. Included the picture of a machine that measures ultrasonic vocalizations for a better understanding. Results: Animals that self-administered methamphetamine mostly released short 22 kHz and predominantly emitted flats and non-trill frequencies of 50kHz. During cocaine self-administration, high-dose (0.71mg/kg/infusion) and low dose (O.355mg/kg/infusion) groups primarily exhibited 50 kHz and 22 kHz USVs, respectively. Also, the results from amphetamine studies show that repeated injection of amphetamine significantly increases the number of 50 kHz emissions. Conclusion: The results provide evidence that rats emit short 22kHz USVs in aversive situations and 50kHz USVs in affective conditions when self-administering methamphetamine and cocaine, which demonstrates rats`` affinity towards these drugs and a useful tool in addiction studies. Although there are few experimental studies regarding utilization of rat USVs in treatment of drug addiction with the Oriental medicine, rat USVs may be used as an objective measuring tool to evaluate the effects of Oriental medicine on addictive behaviors.

척수손상 후 척수 내 GABA 체계의 손실이 중추 신경병증성 통증 유발의 원인이라는 행동학적 및 전기생리학적인 증거

곽영섭,심범,윤덕미,남택상,백광세,임중우 대한마취과학회 2002 Korean Journal of Anesthesiology Vol.42 No.5

신경병성 통증모델쥐에서 산화질소합성효소 억제제가 척수후각세포의 활성도에 미치는 영향

이규래,윤덕미,임중우,곽영섭,정승수,남택상 대한통증학회 2000 The Korean Journal of Pain Vol.13 No.1

Background: Partial nerve injury to a peripheral nerve may induce the development of neuropathic pain which is characterized by symptoms such as spontaneous burning pain, allodynia and hyperalgesia. Though underlying mechanism has not fully understood, sensitization of dorsal horn neurons may contribute to generate such symptoms. Nitric oxide acts as an inter- and intracellular messenger in the nervous system and is produced from L-arginine by nitric oxide synthase (NOS). Evidence is accumulating which indicate that nitric oxide may mediate nociceptive information transmission. Recently, it has been reported that NOS inhibitor suppresses neuropathic pain behavior in an neuropathic pain animal model. This study was conducted to determine whether nitric oxide could be involved in the sensitization of dorsal horn neurons in neuropathic animal model. Methods: Neuropathic animal model was made by tightly ligating the left L5 and L6 spinal nerves and we examined the effects of iontophoretically applied NOS inhibitor (L-NAME) on the dorsal horn neuron's responses to mechanical stimuli within the receptive fields. Results: In normal animals, NOS inhibitor (L-NAME) specifically suppressed the responses to the noxious mechanical stimuli. In neuropathic animals, the dorsal horn neuron's responses to mechanical stimuli were enhanced and NOS inhibitor suppressed the dorsal horn neuron's enhanced responses to non-noxious stimuli as well as those to noxious ones. Conclusions: These results suggest that nitric oxide may mediate nociceptive transmission in normal animal and also mediate sensitization of dorsal horn neurons in neuropathic pain state.