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.

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.

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.

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

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.

백서의 말초 신경병증성 통증모델에서 Capsaicin에 의한 역방향성 임펄스의 차단이 기계적 이질통의발현에 미치는 영향

이청,임중우,임정길,함경돈,박철호,구승우,최윤,신진우 대한통증학회 2004 The Korean Journal of Pain Vol.17 No.01

Background: Nerve impulses that are generated in injured nociceptive fibers and enter the spinal cord are known to cause central sensitization leading to neuropathic pain. Injury-induced impulses that are transmitted antidromically into the peripheral terminals of nociceptive fibers may also cause nociceptors to be sensitized, thus contributing to neuropathic pain. However, this possibility has not yet been tested. The present study was designed to investigate the effects of antidromic impulses on the mechanical allodynic behavior seen in a rat model of neuropathic pain. Methods: Male Sprague-Dawley rats were assigned randomly into one of two groups, i.e., a capsaicin group or a vehicle group. Capsaicin group animals were treated with 1% capsaicin (4μl) in the stump of the distal nerve after severing the fifth left lumbar spinal nerve in order to inhibit delayed and continued antidromic impulses. The vehicle group was treated with same solution without capsaicin. The withdrawal threshold for mechanical allodynia was measured using von Frey hairs in terms of the bending force required to elicit hind-paw withdrawal. Threshold values were compared between the two groups. Results: The capsaicin group showed a statistically significant difference in terms of the paw withdrawal threshold as compared with the corresponding control from 12 days and this remained so until 32 days after treatment. Conclusions: Our results suggest that antidromic impulses developed by nerve injury are partly responsible for the development of mechanical allodynia.

신경병통증 모델 쥐의 척수내에서 흥분성아미노산 수용체

이상암,임중우,박은선,최은진,남택상,백광세 대한신경과학회 1995 대한신경과학회지 Vol.13 No.3

Laser Acupuncture가 동통반응에 미치는 영향

신정순,박창일,임중우 최신의학사 1986 最新醫學 Vol.29 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.

척수손상고양이에서의 Thyrotropin Releasing Hormone이 Somatosensory Evoked Potentials에 미치는 영향에 관한 연구

박종운,이규창,임중우,백광세 대한신경외과학회 1987 Journal of Korean neurosurgical society Vol.16 No.1

The therapeutic goal for the spinal injury has been focused on preventing the secondary ischemic changes because of the poor regeneration of human spinal cord. Naloxone, an antagonist of endogenous opiates, has been clinically used for the purpose of preventing ischemic change and improving the recovery of neurological function after spinal injury. Recently, thyrotropin releasing hormone (TRH), a hypothalamic hormone inducing the thyrotropin secretion in anterior pituitary gland, has been known as a potent stimulator of cardiovascular functions in shock and the neurologic recovery in injuries of central nervous system, however, its underlying mechanism is still obscure. The present study was designed to determine whether TRH was also effective to improve the experimentally induced spinal injury as naloxone did. Somatosensory evoked potentials (SEPs) have used as an index for recovery of neurological function after the spinal injury which was induced by the 400 gm·㎝ contusion of the T -7 spinal level in cats. The results are summerized as follows: 1. SEPs abolished soon after spinal contusion were reappeared 3 hours after injury when either of naloxone(10㎎/㎏) or TRH(4㎎/㎏) was administrated intravenously. Its recovery was completed after 24 hours. 2. The recovery rates of SEPs after treatments of naloxone and TRH were 62.5% and 64.7% of experimental animals, respectively. In conclusion, the present studies confirm the therapeutic benefit of TRH in experimental spinal injury and demonstrate that it is superior to treatment with naloxone. Further studies would be needed to explain the underlying mechanism of TRH effects.