궁둥신경 압좌손상 후 전침이 개 척수 요수부 내 Brain Derived Neurotrophic Factor 발현 및 통증 완화에 미치는 영향
The Effect of Electroacupuncture on Brain Derived Neurotrophic Factor And Pain Decrease in Lumbar Spinal Cord of Dog with Sciatic Nerve Crash Injury
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
본 연구는 개의 궁둥신경을 결찰하여 국소적 신경 손상을 유발시키고, 이에 고빈도(100Hz), 저강도(0.5mA)의 전침자극을 족삼리(ST36), 곡지(LI11), 음릉선(SP9)에 배혈하여 진통효과 및 척수 요수부(L5) 뒷뿔에서 BDNF 발현양상을 관찰하기 위해 면역조직화학염색을 실시해 다음과 같은 결과를 산출하였다. 전침자극군에서 BDNF의 발현은 궁둥신경 결찰로 인해 국소적 신경손상이 유발된 실험동물의 척수 요수부 뒷뿔에서 현저하게 높은 수준이 관찰되었다. 전침자극에 의해 통증역치가 대체로 증가하였는데 48시간 후에 최대의 통증 역치를 보였고(p<.01), 72시간 후부터는 감소하여 전침에 의한 진통작용은 단기적 효과가 있었다. 시간경과에 따라 BDNF 면역 반응성이 증가하였으나 48시간에 최대치를 보인 후(p<.01), 72시간부터는 감소하는 양상을 보였다. BDNF에 면역양성반응을 보인 신경세포들은 큰신경세포(large neuron), 중간신경세포(medium sized neuron), 및 작은 신경세포(small neuron)로 구분하여 관찰되었는데, 작은신경세포가 BDNF 발현의 주된 표적세포였다. 결론적으로 전침자극이 국소적 신경신경 손상 후 진통효과 및 신경가소성을 유발시키는 신경영양성인자인 BDNF 발현에 매우 효과적인 매체인 것으로 판명되었다.
Abstract
The purpose of this study was carried out to investigate the effect of electroacupuncture on BDNF expression in lumbar spinal cord(L5) of dog with sciatic nerve crash injury. 20 male dogs were randomly devided into two groups, a control group and a electroacupuncture group on ST36, LI11 and SP9 with 100Hz and 0.5mA. The dogs were sacrificed at 24h, 48h, 72h and 7day after sciatic nerve crash injury by ligation. The pain threshold was recorded by Analgesy-meter. After making lumbar spinal cord slide sections, they were immunostained with BDNF antisera(1:1000). : The pain threshold of electroacupuncture group was higher than control ne, and maximied at 48h(p<0.01), and had tendency to decrease from 72h. The numbers of BDNF immunoreactive neurons of electroacupuncture group were increased than those of control group. Especially the numbers of BDNF immunoreactive neurons at 24h and 72h(p<0.05), and 48h(p<0.01) were different statistically. The BDNF immunoreactive neurons in lumbar spinal cord expressed by electroacu puncture were classified into large neurons, medium-sized neurons and small neurons, but the small neurons were main target of BDNF expression by electroacupuncture. In onclusion, the increase of pain threshold and numbers of BDNF immunoreactive neurons in lumbar spinal cord of dog showed that electroacupuncture could a good therapeutic tool for analgesia and BDNF expression to prtect central nervous system.
참고문헌 (27)
- 류성룡, "電鍼刺戟의 Collagen 유발 關節炎 動物모델에 대한 鎭痛效果 및 機轉에 관한 硏究-Serotonergic mechanism을 중심으로-", 대한침구학회지, 23(3), pp.77~90 (2006), 대한침구학회
- 손인석, "고빈도 120 Hz 전침이 Carrageenan으로 유발된 흰쥐의 Prostaglandin E2와 척수 N-Methyl-D-Aspartate Receptor 발현에 미치는 영향", 대한침구학회지, 20(3), pp.2~23 (2003), 대한침구학회
- 신홍기, "전침자극이 만성통증을 억제하는 아드레날린성 기전에 대한 연구", 대한한의학회지, 25(3), pp.67~77 (2004), 대한한의학회
- Abe, T., "Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 Is essential for maintenance of neuropathic pain", European Journal of Neuroscience, 22(6), pp.1445~1454 (2005)
- Alder, J., "Early presynaptic and late postsynaptic components contribute independently to brain -derived neurotrophic factor-induced synaptic plasticity", Joural of Neuroscience, 25(12), pp.3080~3085 (2005)
- Bleakman, D, "Glutamate receptors and pain", Seminar in Cell and Developmental Biology, 17(5), pp.592~604 (2006)
- Frim, D. M., "Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat", Processings of the National Academy of Sciences in the USA, 91(11), pp.5104~5108 (1994)
- Geng, S. J., "Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation", Experimental Neurology, 222(2), pp.256~266 (2010)
- Kerr, B. J., "Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA -evoked responses in the rat spinal cord", Journal of Neuroscience, 19(12), pp.5138~5148 (1999)
- Lapchak, P. A., "Chronic intranigral administration of brain-derived neurotrophic factor produces striatal dopaminergic hypofunction in unlesioned adult rats and fails to attenuate the decline of striatal dopaminergic function following medial forebrain bundle transection", Neuroscience, 53(3), pp.639~650 (1993)
- Liang, X. B., "Long-term high-frequency electro-acupuncture stimulation prevents neuronal degeneration and up-regulates BDNF mRNA in the substantia nigra and ventral tegmental area following medial forebrain bundle axotomy", Molecular Brain Research, 108(1), pp.51~59 (2002)
- Lin, S. Y, "BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities", Molecualr Brain Research, 55(1), pp.20~27 (1998)
- Lin, S. Y., "Brain-derived neurotrophic factor enhances association of protein tyrosine phosphatase PTP1D with the NMDA receptor subunit NR2B in the cortical postsynaptic density", Molecular Brain Research, 70(1), pp.18~25 (1999)
- Liu, X. G., "Long-term potentiation of C-fiber -evoked potentials in the rat spinal dorsal horn is prevented by spinal N-methyl-D-aspartic acid receptor blockage", Neuroscience Letters, 191(1), pp.43~46 (1995)
- Lu, W., "Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons", Journal of Neuroscience, 29(1), pp.243~254 (2001)
- Marcol, W, "BDNF contributes to animal model neuropathic pain after peripheral nerve transection", Neurosurgery Reviews, 30(3), pp.235~243 (2007)
- Matayoshi, S., "Actions of brain-derived neurotrophic factor on spinal nociceptive transmission during inflammation in the rat", Journal of Physiology, 569(2), pp.685~695 (2005)
- Nakazawa, T., "Characterization of Fynmediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor", Journal of Biological Chemistry, 276(1), pp.693~699 (2001)
- Nakazawa, T, "Regulation of NMDA receptor function by Fyn-mediated tyrosine phosphorylation", Journal of Neuroscience, 22(5), pp.165~167 (2002)
- Obata, K., "BDNF in sensory neurons and chronic pain", Neuroscience Research, 55(1), pp.1~10 (2006)
- Pezet, S., "Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn", Molecular and Cellular Neuroscience, 21(4), pp.684~695 (2002)
- Pezet, S., "BDNF: a neuromodulator in nociceptive pathways?", Brain Research Reviews, 40(1), pp.240~249 (2002)
- Shults, C. W., "BDNF attenuates the effects of intrastriatal injection of 6-hydroxydopamine", NeuroReport, 6(8), pp.1109~1112 (1995)
- Svendsen, F, "Long-term potentiation in single wide dynamic range neurons induced by noxious stimulation in intact and spinalized rats", Progress in Brain Research, 129, pp.153~161 (2000)
- Thompson, S. W., "Brain-derived neurotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord", Processings of the National Academy of Sciences in the USA, 96(14), pp.7714~7718 (1999)
- Tigaret, C. M., "Subunit dependencies of N-methyl-D-aspartate(NMDA) receptor-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization", Molecular Pharmacology, 69(4), pp.1251~1259 (2006)
- Woolf, C. J., "Central sensitization: uncovering the relation between pain and plasticity", Anesthesiology, 106(4), pp.864~867 (2007)