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.

신경손상에 의해 유발된 과민통반응에서 말초 케모카인 CCL3의 역할

임중우 ( Joong Woo Leem ),이현주 ( Hyun Joo Lee ),남택상 ( Taick Sang Nam ),윤덕미 ( Duck Mi Yoon ) 대한통증학회 2008 The Korean Journal of Pain Vol.21 No.3

교감신경 중재 통증 보유 모델 쥐에서 교감신경 활동에 의한 배근절세포의 흥분성

임중우(Joong Woo Leem),강민정(Min Jung Kang),백광 대한통증학회 1996 The Korean Journal of Pain Vol.9 No.1

N/A In a normal state, sympathetic efferent activity does not elicit discharges of sensory neurons, whereas it becomes associated with and excites sensory neurons in a patho- physiological state such as injury to a peripheral nerve. Although this sympathetic-sensory interaction is reportedly adrenergic, involved subtypes of adrenoreceptors are not yet clearly revealed. The purpose of this study was to determine which adrenoreceptor sub- types were involved in sympathetic-sensory interaction that was developed in rats with an experimental peripheral neuropathy. Using rats that received a tight ligation of one or two of L4-L6 spinal nerves 10-15 days previously, a recording was made from afferent fibers in microfilaments teased from the dorsal root that was in continuity with the ligated spinal nerve. Electrical stimulation of sympathetic preganglionic fibers in T13 or Ll ventral root (50 Hz, 2-5 mA, 0.5 ms pulse duration, l0sec) was made to see if the activity of recorded afferents was modulated. About half of afferents showing spontaneous discharges responded to sympathetic stimu- lation, and had the conduction velocities in the A-fiber range. Most of the sympathetically induced afferent responses were excitation. This sympathetically induced exciitation oc- curred in the dorsal root ganglion (DRG), and was blocked by yohimbine (a.. blocker), nei- ther by propranolol 0 blocker) nor by prazosine (ai blocker). The results suggest that after spinal nerve ligation, sympathetic efferents interact with sensory neurons having A-fiber axons in DRG where adrenaline released from sympathetic nerve endings excites the activity of sensory neurons by acting on 2-adrenoreceptors. This 2-adrenoreceptor mediated excitation of sensory neurons may account for sympathetic in- volvement in neuropathic pain.

신경병증성통증 모델쥐에서 뇌간핵 부위에 미세 주입한 Bicuculline에 의한 척수후각세포의반응도 억제

임중우(Joong Woo Leem),최 윤(Yoon Choi),이재환(Jae 대한통증학회 1998 The Korean Journal of Pain Vol.11 No.1

N/A Background: The present study was conducted to investigate effects of mieroinjection of bicuculline, GABA-A receptor antagonist, into the brain stem nuclei on the dorsal horn neuron responsiveness in rats with an experimental peripheral neuropsthy. Methods: An experimental neuropathy was induced by a unilateral ligation of L5-L6 spinal nerves of rats. After 2-3 weeks after the surgery, single-unit recording was made from wide dynamic range (WDR) neurons in the spinal cord dorsal horn. Results: Responses of WDR neurons to both noxious and innocuous mechanical stimuli applied to the somatic reeeptive fields were enhanced on the nerve injured side. These enhanced responsiveness of WDR neurons were suppressed by microinjection of bicuculline into periaqueductal gray(PAG) or nucleus reticularis gigantocellularis(Gi). A similar suppression was also observed when morphine was microinjected into PAG or Gi. Suppressive actian by Gi-bicuculline was reversed by naloxonazine, p -opioid receptor antagonist, microinjected into PAG whereas PAG-bicuculline induced suppression was not affected by naloxonazine injection into Gi. Gi-bicuculline induced suppression were reversed by a transection of dorsolateral funiculus(DLF) of the spinal cord. Conclusions: The results suggest that endogenous opioids, via acting on GABAergic interneurons in PAG and Gi, may be involved in the control of neuropathic pain by activating the descending inhibitory pathways that project to the spinal dorsal horn through DLF to inhibit the responsiveness of WDR neurons.

말초신경 자극시 자극의 강도, 빈도 및 기간의 변화가 동통반응에 미치는 영향

백광세,임중우,김인교,이승일,강두희,Paik, Kwang-Sea,Leem, Joong-Woo,Kim, In-Kyo,Lee, Seung-Il,Kang, Doo-Hee 대한생리학회 1985 대한생리학회지 Vol.19 No.2

Previously, we had reported that the electrical stimulation of peripheral nerve with stimlatory parameters of 20 V strength and 2 Hz frequency for 60 min resulted in reducing the pain reaction. The present study was performed to evaluate if the pain reaction was affected by the peripheral nerve stimulation with different stimulatory parameters in the decerebrated cat. The flexion reflex was used as an index of the pain reaction. The reflex was elicited by stimulating the sural nerve (stimulus strength of 20 $V\;\times\;0.5$msec) and recorded as a compound action potential from the motor nerve innervated to the posterior biceps femoris muscle. The common perneal nerve was selected as a peripheral nerve on which the electrical stimulation of various intensities and frequencies was applied. The results are summarized as follows : 1) The peripheral nerve stimulation with 100 mV strength, regardless of frequencies, did not affect the pain reaction induced by the sural nerve stimulation. 2) When the stimulus of 1V intensity and slow frequency (2 Hz) was applied to the peripheral nerve for 30 min or 60 min, the pain reaction was significantly reduced comparing to the control. However, this reduced pain reaction by the peripheral nerve stimulation was not reversed by the injection of naloxone (0.02 mg/kg) 3) High frequency stimulus (60 Hz) of 1V intensity for 30 or 60 min did not show any effects of affecting the pain reaction. These results suggest that the stimulus of relatively high intensity (at least 1V) and low frequency (2 Hz) is needed to elicite the analgesic effect by the peripheral nerve stimulation. By the 1V stimulus, $A\delta$ nerve fiber is activated. Therefore, an $A\delta$ or smaller nerve fibers must be activated for showing analgesia by the peripheral nerve stimulation. However, the mechanism of analgesia by the $A\delta$ nerve activation alone was not related to the endogeneous morphine system since the reduced pain reaction by the $A\delta$ fiber activation alone was not reversed by the treatment of naloxone.

Vanadate가 골격근 sarcoplasmic reticulum의 $Ca^{++}-ATPase$ 및 $Ca^{++}\;uptake$에 미치는 영향

주순재,한경희,임중우,강두희,Joo, Soon-Jae,Han, Kyung-Hee,Leem, Joong-Woo,Kang, Doo-Hee 대한생리학회 1986 대한생리학회지 Vol.20 No.2

Since it has been reported that vanadate inhibits $Ca^{++}-ATPase$ activity without affecting $Ca^{++}$ uptake, this study was undertaken to investigate the effects of vanadate on $Ca^{++}-ATPase$ activity and $Ca^{++}$ uptake in the sarcoplasmic reticulum of rat skeletal muscle. The following results were obtained. 1) $Ca^{++}$ activated ATPase activity of the intact sarcoplasmic reticulum was significantly inhibited when vanadate was added to the incubation medium at concentration greater than $10^{-6}\;M$. However $Mg^{++}$-ATPase activity of the intact SR was not affected by vanadate at concentrations ranging from $10^{-7}\;to\;10^{-4}\;M.$ Similarly, $Ca^{++}-ATPase$ activity in sonicated sarcoplasmic reticulum was significantly reduced by vanadate at a concentration $10^{-7}$ M or higher. 2) The uptake of $Ca^{++}$ by isolated sarcoplasmic reticulum was also inhibited by vanadate under the conditions where the turnover rate of $Ca^{++}-ATPase$ was made to increase. These results suggest that the inhibition of $Ca^{++}$ uptake by vanadate may be correlated with that of $Ca^{++}-ATPase$ if experimental conditions are properly set.

백서의 말초신경 통증 모델에서 신경결찰 전 말초에 주입된 Bupivacaine 이 기계적 통각과민의 발현에 미치는 영향

정용보(Yong Bo Chung),임중우(Joong Woo Leem),정은정(Eun Jung Chung),이정찬(Jung Chan Lee),최윤(Yoon Choi) 대한통증학회 2001 The Korean Journal of Pain Vol.14 No.1

N/A Background: Although several mechanisms of causalgia, which results from a partial injury to the peripheral nerve trunk, have been proposed, whether or not antidromic impulses from the injured neurons contribute to the development of the mechanical hyperalgesia has not been studied. The purpose of this experiment is was to investigate the role of antidromic impulses to the peripheral sensory receptor site on the development of mechanical hyperalgesia in a rat model of peripheral neuropathy. Methods: Rats were prepared with tight ligation of by tightly ligating the left fifth and sixth lumbar spinal nerves. The effect of bupivacaine pretreatment on the development of mechanical hyperalgesia was evaluated by injecting 0.5% bupivacaine (0.3 ml) into the plantar surface of the left hind paw before the skin incision was made. For the control group, normal saline (0.3 ml) was injected instead of bupivacaine. To measure the mechanical hyperalgesia, paw withdrawal thresholds were measured using a series of von Frey hairs. Mechanical hyperalgesia was measured a the day before, and 1, 2, 3, 4, 7, and 14 days after the surgery. Results: The control group showed decreased withdrawal thresholds from the day after the surgery (the values were 14.0 ± 0.5, 8.9 ± 1.3, 8.4 ± 1.6, 6.9 ± 1.2, 8.8 ± 1.5, 10.5 ± 1.3, and 8.6 ± 1.3 g; at -1, 1, 2, 3, 4, 7, and 14 days after the surgery, respectively). However, withdrawal thresholds of the bupivacaine-pretreated group showed increased withdrawal thresholds for three days after the surgery (14.5 ± 0.3, 12.6 ± 1.4, 12.7 ± 1.1, 10.5 ± 1.3 g; at 1, 1, 2, 3 days after the surgery). Conclusions: Our result suggests that antidromic impulses to the peripheral sensory receptors are at least partly responsible for the initial development of mechanical hyperalgesia in a rat model of peripheral neuropathy.

공간기억의 습득에 있어서 해마와 두정엽후위의 역할

심범(Beom Shim),임중우(Joong-Woo Leem),남택상(Taick-Sang Nam),백광세(Kwang-Se Paik),이배환(Bae-Hwan Lee),박용구(Yong-Gou Park) 한국인지과학회 1999 인지과학 Vol.10 No.4

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.

Vanadate가 골격근 sarcoplasmic reticulum의 Ca⁺⁺-ATPase 및 Ca⁺⁺ uptake에 미치는 영향

주순재(Joo, Soon-Jae),한경희(Han, Kyung-Hee),임중우(Leem, Joong-Woo),강두희(Kang, Doo-Hee) 대한생리학회 1986 대한생리학회지 Vol.20 No.2

Since it has been reported that vanadate inhibits Ca⁺⁺-ATPase activity without affecting Ca⁺⁺ uptake, this study was undertaken to investigate the effects of vanadate on Ca⁺⁺-ATPase activity and Ca⁺⁺ uptake in the sarcoplasmic reticulum of rat skeletal muscle. The following results were obtained. 1) Ca⁺⁺ activated ATPase activity of the intact sarcoplasmic reticulum was significantly inhibited when vanadate was added to the incubation medium at concentration greater than 10^-6 M. However Mg⁺⁺-ATPase activity of the intact SR was not affected by vanadate at concentrations ranging from 10^-7 to 10^-4 M. Similarly, Ca⁺⁺-ATPase activity in sonicated sarcoplasmic reticulum was significantly reduced by vanadate at a concentration 10^-7 M or higher. 2) The uptake of Ca⁺⁺ by isolated sarcoplasmic reticulum was also inhibited by vanadate under the conditions where the turnover rate of Ca⁺⁺-ATPase was made to increase. These results suggest that the inhibition of Ca⁺⁺ uptake by vanadate may be correlated with that of Ca⁺⁺-ATPase if experimental conditions are properly set.