신경병성통증의 원인과 역학

서범천 대한의사협회 2021 대한의사협회지 Vol.64 No.7

Background: Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at the peripheral or central level. In most cases, neuropathic pain is associated with poor general health and has a problem of suboptimal response to medical treatment. This review will discuss the neurologic and non-neurologic conditions that cause neuropathic pain and the results of epidemiologic studies on neuropathic pain. Current Concepts: Epidemiology would be a useful clinical tool for designing management and prevention strategies for various neuropathic pain syndromes. Validated neuropathic pain screening questionnaires are widely used as useful tools for the epidemiologic study of neuropathic pain. There are also validated Korean versions of these questionnaires. The overall prevalence of neuropathic pain was estimated at 6.9-10%. Common neuropathic pain syndromes include diabetic neuropathy, herpes zoster, and trigeminal neuralgia. In addition, neuropathic pain can also occur in central nervous system disorders such as spinal cord injury or stroke, and other conditions like cancerous diseases, intervertebral disc disease, and joint diseases. Discussion and Conclusion: Neuropathic pain does not respond well to medical treatment, which leaves both patients and physicians are less satisfied with such treatments. Therefore, physicians must identify the causes of the pain, explain them to the patient, and proceed with the treatment together with patients.

말초신경 손상에 의한 신경병증성 통증에 TENS가 미치는 효과

이순현 ( Soon Hyun Lee ),송창호 ( Chang Ho Song ) 대한물리의학회 2013 대한물리의학회지 Vol.8 No.1

PURPOSE: To identify the effects of single trial transcutaneous electrical nerve stimulation (TENS) application on chronic neuropathic pain and the repeated TENS application to development of neuropathic pain following peripheral nerve injury. METHODS: First, 20 rats were given the median nerve ligation to induce chronic neuropathic pain. After the ligation, neuropathic pain was assessed by measuring the forepaws withdrawal threshold to von Frey filaments for 3 weeks. Afterward, rats were randomly divided into TENS group and placebo-TENS group. TENS (frequency 100Hz, pulse width 200㎲) was applied to the forearm for 20 minutes. Second, 34 rats were randomly allocated into two group after median nerve ligation: TENS group and placebo-TENS group. Both interventions were applied to the forearm for 20 minutes from 1 day to 3 weeks after injury. Neuropathic pain to mechanical was measured on each rat for 3 weeks. RESULTS: Exeprimental rats showed a clear neuropathic pain-like behaviors, such as reduced forepaw withdrawal threshold to mechanical stimulation for 3 weeks, after median nerve ligation. And, TENS decreased effectively the chronic neuropathic pain originated from median nerve injury. TENS also diminished the development of neuropathic pain after nerve injury. CONCLUSION: Our animal model studying for neuropathic pain following median nerve injury may be useful to investigate peripheral neuropathic pain in human. Also, TENS may be used to mediate chronic neuropathic pain and to prevent the development of neuropathic pain following median nerve injury.

신경병통증의 선별과 척도화를 위한 한국어 신경병통증설문지 개발: 예비연구

윤동주,오지영,김병조,임정근,배종석,정두신,주인수,박민수,김병준 대한신경과학회 2012 대한신경과학회지 Vol.30 No.1

Background: The pain-screening questionnaire is a self-reported description of the intensity and nature of pain. This study aimed to develop the Korean Neuropathic Pain Questionnaire (KNPQ) and to assess its reliability and validity regarding the diagnosis of neuropathic pain. Methods: Four screening tools and two rating scales were translated and modified to develop the preliminary KNPQ. Following a development phase and a pilot study, we generated the final 25-item version of the KNPQ. Each item was rated on a numerical scale of 0–10. The validation procedure was performed in 62 patients with neuropathic pain (21 with central pain and 41 with peripheral pain) and in 34 patients with nonneuropathic pain. The internal consistency between items was assessed to determine the reliability of the KNPQ, and its concurrent validity was determined by evaluating the relationship between the Visual Analogue Scale (VAS) and KNPQ scores. Results: The KNPQ was not influenced by age, sex, or pain duration. The 25-item questionnaire demonstrated high internal consistency. The total score of the KNPQ was correlated with the global pain intensity on a VAS. These items were able to differentiate neuropathic pain from nonneuropathic pain with a sensitivity of 84% and a specificity of 44%(when using a cut-off point of 46). Conclusions: The newly developed KNPQ may be used for the initial screening of neuropathic pain patients. However,it cannot be used to differentiate central neuropathic pain from peripheral neuropathic pain.

Clinical Aspects of Screening Test Tools for Central Neuropathic Pain in Patients with Thalamic Stroke

Lee, In Hee,Kim, Yoon Nyun,Son, Chang Sik,Kwon, Yong Hyun,Kim, Min Soo,Seo, Suk Tae The Society of Physical Therapy Science 2011 JOURNAL OF PHYSICAL THERAPY SCIENCE Vol.23 No.5

<P>[Purpose] The purpose of this study was to investigate clinical aspects of screen test tools for central neuropathic pain in thalamic stroke patients. [Subjects and Methods] Seven thalamic stroke patients were recruited as subjects. To classify the subjects into central neuropathic pain and non-neuropathic pain groups, the Leeds assessment of neuropathic symptoms and signs (LANSS) was used. Four patients were classified as having central neuropathic pain. To evaluate the central neuropathic pain, the quantitative somatosensory test, the median nerve somatosensory evoked potentials (SEPs), magnetic resonance imaging (MRI), and functional MRI (fMRI) were performed on average 31.5 months after stroke. [Results] The quantitative somatosensory test did not show a correlation between the central neuropathic pain group and the non-neuropathic pain group. The SEPs on the affected side showed a response in one of the patients without central neuropathic pain, and responses on the unaffected side were normal for all of the patients. MRI-based thalamic localization data indicate that this method is limited in its ability to distinguish the central neuropathic pain in thalamic stroke patients. Results of fMRI show that the secondary somatosensory areas of the central neuropathic pain group were more activated than those of non-neuropathic pain group. [Conclusion] Based on the results, we verified that functional MRI is useful for evaluating the central neuropathic pain in thalamic stroke patients.</P>

신경병성통증의 평가와 진단

오지영 대한의사협회 2021 대한의사협회지 Vol.64 No.7

Background: Thorough evaluation and an accurate diagnosis of neuropathic pain are essential for effective treatment. The therapeutic approach and choice of medication for neuropathic pain are different from those for other kinds of nociceptive pain. Therefore, this study aimed to present the current evaluation and diagnostic methods for neuropathic pain. Current Concepts: Grading of the certainty of the presence of neuropathic pain according to the results of clinical history, neurological examination, and confirmatory tests improves the diagnosis of neuropathic pain. The Leeds Assessment of Neuropathic Symptoms and Signs, Neuropathic Pain Questionnaire, Douleur Neuropathique en 4 Questions, and PainDETECT are mainly used for neuropathic pain screening. During physical examination, sensory nerve function tests are more critical than other nervous system examination items, including the test of the sense of touch with a cotton swab and the sense of vibration with a tuning fork. In addition, pain sensation using pins and temperature sensation using cold metal are tested to check for nociceptive pathway abnormalities. Diagnostic tests include imaging tests, nerve conduction tests, and other neurophysiological tests, such as quantitative sensory function tests, autonomic nerve function tests, and blood tests. Discussion and Conclusion: To diagnose neuropathic pain, physicians should first determine whether patient symptoms match the characteristics of neuropathic pain. If there is a possibility of neuropathic pain, physicians should perform a neurological screening examination and a proper diagnostic test to identify the cause of pain.

The Neuromodulation of Neuropathic Pain by Measuring Pain Response Rate and Pain Response Duration in Animal

Kim, Jinhyung,Lee, Sung Eun,Shin, Jaewoo,Jung, Hyun Ho,Kim, Sung June,Chang, Jin Woo The Korean Neurosurgical Society 2015 Journal of Korean neurosurgical society Vol.57 No.1

Objective : Neuropathic pain causes patients feel indescribable pain. Deep Brain Stimulation (DBS) is one of the treatment methods in neuropathic pain but the action mechanism is still unclear. To study the effect and mechanism of analgesic effects from DBS in neuropathic pain and to enhance the analgesic effect of DBS, we stimulated the ventral posterolateral nucleus (VPL) in rats. Methods : To observe the effect from VPL stimulation, we established 3 groups : normal group (Normal group), neuropathic pain group (Pain group) and neuropathic pain+DBS group (DBS group). Rats in DBS group subjected to electrical stimulation and the target is VPL. Results : We observed the behavioral changes by DBS in VPL (VPL-DBS) on neuropathic pain rats. In our study, the pain score which is by conventional test method was effectively decreased. In specific, the time of showing withdrawal response from painful stimulation which is not used measuring method in our animal model was also decreased by DBS. Conclusion : The VPL is an effective target on pain modulation. Specifically we could demonstrate changes of pain response duration which is not used, and it was also significantly meaningful. We thought that this study would be helpful in understanding the relation between VPL-DBS and neuropathic pain.

Decoding neuropathic pain severity using distinct patterns of corticolimbic metabotropic glutamate receptor 5

Chung, Geehoon,Kim, Chae Young,Kim, Sang Jeong ACADEMIC PRESS 2019 NEUROIMAGE Vol.190 No.-

<P><B>Abstract</B></P> <P>Susceptibility to neuropathic pain and the degree of pain amplification vary among individuals. However, methods for objective evaluation of pain status have not been well established. Using an animal model, we identified the brain signature of neuropathic pain, and developed a method for the objective evaluation of pain degree. We analyzed paw withdrawal thresholds from rats that were subjected to right L5 spinal nerve ligation (SNL) surgery, and regressed them to the metabotropic glutamate receptor 5 (mGluR5) availability levels in the brain using [11C] ABP688 PET image data from our previous research. We found clusters with a significant correlation to paw withdrawal threshold localized in brain areas involved in sensory, cognitive, and affective aspects of pain processing. Strikingly, mGluR5 availability levels in the identified brain regions showed distinct patterns in the neuropathic pain group but not in the control group. We successfully elucidated the degree of pain-sensing behavior using the neuropathic pain-specific pattern of the mGluR5 availability. Our study provides new insight into the signature of neuropathic pain in the brain, and offers a novel diagnostic method for objectively decoding the status of individual neuropathic pain.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Susceptibility to neuropathic pain and the degree of pain vary among individuals. </LI> <LI> The sensory and limbic mGluR5 availability levels correlate with the pain behavior. </LI> <LI> The corticolimbic mGluR5 availability levels form distinct patterns in pain state. </LI> <LI> Pain severity could be predicted using the brain mGluR5 patterns. </LI> </UL> </P>

환도혈(環跳穴) 오공약침(五蚣藥鍼) 자극(刺戟)이 백서(白鼠)의 신경병리성(神經病理性) 통증(痛症) 억제(抑制)에 미치는 영향(影響)

김성남,김성철,최회강,소기숙,임정아,황우준,문형철,최성용,이상관,나창수,Kim, Sung-nam,Kim, Sung-chul,Choi, Hoi-kang,So, Ki-suk,Lim, Jeong-a,Hwang, Woo-jun,Moon, Hyung-cheol,Choi, Sung-yong,Lee, Sang-kwan,Na, Chang-su 대한침구의학회 2004 대한침구의학회지 Vol.21 No.3

Objective : Neuropathic pain can be caused by a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It is not clear that scolopendrid aqua-acupuncture can control neuropathic pain effectively. The purpose of this study is to examine if scolopendrid aqua-acupuncture may be effective to the neuropathic pain (mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, scolopendrid aqua-acupuncture was injected at Hwando(GB30) one time a day for one week. After that the author examined the withdrawl response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results & Conclusion : 1. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of mechanical allodynia in SHA-1, SHA-2 and SAH-3 group as compared with control group. 2. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in SHA-1, SHA-2 and SAH-3 group as compared with control group. 3. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and control group(p=0.01), sham and SHA-3 group(p=0.026), control group and SHA-1 group(p=0.01), control group and SHA-2 group(p=0.024) in the c-fos expression. 4. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and SHA-3 group(p=0.010), control group and SHA-3 group(p=0.006) in the WBC count.

백서(白鼠)에서 오공약침(蜈蚣藥鍼)이 신경병증성(神經病症性) 통증(痛症)에 미치는 영향(影響)

이삼로 ( Sam Ro Lee ),김성철 ( Sung Chul Kim ),구성태 ( Sung Tae Koo ),김성남 ( Sung Nam Kim ),황우준 ( Woo Jun Hwang ),이건목 ( Geon Mok Lee ),조남근 ( Nam Geun Cho ),임규상 ( Kyu Sang Lim ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.2

Objectives: In the present study, the effect of Scolopendrid Water-Alcohol Extract (SWAE) applied to acupuncture point BL23 (Shinsu) on the neuropathic pain was examined. A common source of persistent pain in humans is the neuropathic pain. Anti-convulsant drugs are used to treat the neuropathic pain. In the oriental medicine, Scolopendrid was used for long time to treat convulsant syndrome and back pain, etc. Methods: On the bases of the Scolopendrid clinical application, the effect of SWAE applied to the acupuncture point was tested in the rat model of neuropathic pain. Neuropathic pain was induced by tight ligation of L5 spinal nerve. When rats developed pain behaviors, One hundred microliter of SWAE was applied into the ipsilateral BL23 point at a dose of 10 mg/ml under enflurane anesthesia. The foot withdraw latency of the hind limb was measured for an indicator of pain level after each manipulation. Results: SWAE injection increased the mechanical threshold of the foot in the rat model of neuropathic pain significantly for the duration of 4h, suggesting a partial alleviation of pain. SWAE applied to BL23 point produced a significant improvement of mechanical sensitivity of the foot lasting for at least 4h. However, neither contralateral BL23 point, ST25 (Chonchu) point, nor LR3 (Taechung) point produce as much increase of mechanical sensitivity as ipsilateral BL23 point. And, this increase of mechanical sensitivity was dose-dependent. The improvement of mechanical threshold was interpreted as an analgesic effect. In addition, the analgesic effect of Scolopendrid 4 mg/kg injection is equivalent to that of gabapentin 50 mg/kg injection. The relations between SWAE-induced analgesia and endogenous nitric oxide(NO), inducible NO synthase (iNOS)/neuronal NO synthase (nNOS) were also examined. Results were turned out that both NO production and nNOS/iNOS protein expression which are increased by nerve injury were suppressed by SWAE injection applied to BL23 point. Conclusions: The data suggest 1) that SWAE produces a potent analgesic effect on the neuropathic pain model in the rat and 2) that SWAE-induced analgesia modulate endogenous NO through the suppression of nNOS/iNOS protein expression.

신경병증성 통증의 처리 과정에 있어 중추신경계의 가소성 변화 비교

권민지 ( Minjee Kwon ) 한국감성과학회 2021 감성과학 Vol.24 No.2

국제통증연구학회(IASP)에 따르면, 신경병증성 통증은 정상 조건에서 중추신경계에 유해한 정보를 전달하는 신경계 기능 장애로 특징 지워진다. 이런 통증은 말초 혹은 중추 신경계에 확인 가능한 병변이 있는 질환과 어떠한 신경에도 병변이 없는 상태에서 발생하는 상황으로 나누어 볼 수 있다. 두 가지 상황 모두 장기적이고 만성적인 변화과정을 겪게 되며, 결과적으로 신경계가 부적절하게 적응하여 치유되기 어려운 만성통증 증후군으로 발전할 수 있다. 그러나 이러한 통증 치료는 진단에서부터 치료까지의 과정이 어려운 탓에 현재까지도 특별한 해결방안이 부족한 실정이다. 최근 자기공명영상(fMRI), 양전자방출단층촬영법(PET), 광영상(optical imaging) 등 영상분석기술이 발달함에 따라 통증을 유발할 수 있는 유해 자극에 대한 중추신경계의 반응을 영상화하는 연구가 증가하고 있다. 이러한 영상 기법들을 통해 통증을 해석하고 처리하는 뇌 영역에서 시냅스 간 가소성 변화가 일어나고 있음을 확인하였으며, 신경병증성 통증을 비롯한 만성통증과 학습과의 상호 작용을 이해하는 데 많은 도움을 주고 있다. 본 연구는 병리적 통증의 기전과 통증 자극에 따른 뇌의 구조적, 기능적 변화에 대해 최근까지 밝혀진 연구들을 소개하고자 한다. 만성적 통증의 정의와 발생기전을 되짚고 새로운 연구 동향을 살펴보는 것은 통증을 완화할 수 있는 방안을 강구하는 데 도움이 될 것으로 사료된다. According to International Associating for the Study of Pain (IASP) definition, neuropathic pain is a disorder characterized by dysfunction of the nervous system that, under normal conditions, mediates virulent information to the central nervous system (CNS). This pain can be divided into a disease with provable lesions in the peripheral or central nervous system and states with an incorporeal lesion of any nerves. Both conditions undergo long-term and chronic processes of change, which can eventually develop into chronic pain syndrome, that is, nervous system is inappropriately adapted and difficult to heal. However, the treatment of neuropathic pain itself is incurable from diagnosis to treatment process, and there is still a lack of notable solutions. Recently, several studies have observed the responses of CNS to harmful stimuli using image analysis technologies, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and optical imaging. These techniques have confirmed that the change in synaptic-plasticity was generated in brain regions which perceive and handle pain information. Furthermore, these techniques helped in understanding the interaction of learning mechanisms and chronic pain, including neuropathic pain. The study aims to describe recent findings that revealed the mechanisms of pathological pain and the structural and functional changes in the brain. Reflecting on the definition of chronic pain and inspecting the latest reports will help develop approaches to alleviate pain.