아프냐? 통증과 고통 느끼는 경로 다르다 How do we learn to stay away from potential harm?
在美 한국인 과학자,
류머티스 관절염 치료제 개발 가능성 열어
Won't do that again: What brain circuits are at work when we learn from experience not to go into
harms way?
edited by kcontents
케이콘텐츠 편집
재미(在美) 한국인 과학자가 통증을 인식하고 고통스러운 감정을 느끼는 원리를 밝히는 데 성공했다.
한성 워싱턴대 하워드휴즈의학연구소 박사팀은 뇌에서 통증을 감각으로 인식하는 경로와 고통스러운 느낌을 받는 경로가 별개로 존재한다는 사실을 알아내고 국제학술지 ‘셀’ 16일자에 발표했다. 사람은 본능적으로 뜨거워 보이는 물체를 바로 잡지 않고 살짝 건드려보고 어떻게 할지 판단한다. 과거에 고통을 유발한 상황이 뇌에 저장돼 있기 때문이다.
지금까지 인체가 통증을 인지하는 경로와 그로 인한 감정적인 반응인 고통이 서로 다른 경로를 통해 일어날 것이라고 생각해 왔지만 구체적으로 밝혀지지는 않았다.
연구진은 사람과 쥐의 뇌에 동일하게 존재하는 ‘CGRP’라는 신경전달물질이 많이 분포하는 ‘팔곁핵(Parabrachial nuclues)’과 ‘편도핵(Amygdala)’이 통증을 인식하고 고통을 느끼며 기억하는 데 영향을 미칠 것으로 추정하고 쥐를 이용해 실험을 진행했다.
실험 결과 유전자를 조작해서 CGRP가 들어 있는 신경세포를 억제한 쥐는 고통스러운 자극을 받아도 달아나거나 그 자리에 멈춰버리는 공포 반응을 보이지 않았다. 또 특정 상황에서 고통을 받았던 쥐는 보통 그 상황이나 장소를 기억해 공포 반응을 보이는 반면 CGRP 신경세포를 억제한 쥐는 아무런 거리낌 없이 움직였다.
반면 이 쥐는 높은 온도나 기계적인 자극에 대해서는 정상적인 통증 반응을 보였다. 반대로 CGRP 신경세포를 활성화시키면 공포상황이 아니어도 두려워하는 반응을 보였다. 통증 인식과 감정적인 고통이 별개로 처리됨을 보여준 것이다.
연구진은 이어서 통증으로 인한 공포 기억이 CGRP 수용체를 가진 편도핵 신경세포에 저장된다는 사실도 확인했다. 편도핵에서 CGRP 수용체를 가진 신경세포를 억제했을 때는 통증을 가해도 공포 기억이 저장되지 않는 반면 이 세포를 활성화시키면 정상 상황에서도 두려움을 나타냈다.
한 연구원은 본보와의 e메일 인터뷰에서 “감정 변화를 유발하는 통증 경로를 밝힌 것”이라며 “만성 편두통과 류머티스 관절염 같은 만성 통증관련 질환을 더욱 효과적으로 치료할 수 있는 신약 개발의 단초가 될 것”이라고 말했다. 동아사이언스 최영준 기자 jxabbey@donga.coma |
How do we learn to stay away from potential harm?
Brain circuitry that underlies threat avoidance studied
By Michael McCarthy | HSNewsBeat
A nervous system circuit that transmits the emotional component of pain and that leads to avoiding threats in the environment has been discovered. The findings from the University of Washington-led study are published online July 16 by the journal Cell.
The brain circuit that is created from experience to
help avoid future harm Palmiter Lab
The brain circuit that is created from experience to help avoid future harmThe brain circuit that is created from experience to help avoid future harm
Their report advances the understanding of how we learn from experiences and could lead to new, more effective treatments for pain, particularly those often associated with significant emotional or psychological component such as migraine, post traumatic stress disorder and chronic arthritis pain. Sung Han, a research associate in Richard Palmiter’s lab in the UW Department of Biochemistry, was the paper’s lead author.
Pain signals travel via two main pathways. One, the sensory discriminative pain pathway, travels from the spinal cord to the brain and helps us sense the pain and locate its source. The other, the affective motivational pain pathway, colors the pain with emotion so that we perceive it as unpleasant, and motivates us to avoid the source of the discomfort.
It has been hypothesized that affective motivational or emotional pain pathway involved a structure in the midbrain called the parabrachial nucleus (PBN), but this had never been proved. Han, Palmiter and their colleagues suspected it was. They were particularly interested cells in this structure that produced a neurotransmitter, called calcitonin gene-related peptide (CGRP), that extended axons to cells in the amygdala that have receptors for the CGRP.
The questions for the researchers were whether these CGRP-expressing neurons in the PBN were indeed responsible for relaying the affective motivational pain signals to the CCRP-receptor cells in amygdala and whether this circuit helped create threat memory. The amygdala is a tear-shaped collection of cells deep in the brain. It is believed to process emotions, including fear and pleasure.
The researchers used techniques to selectively switch the CGRP cells "on" or "off" and see if that changed how mice responded to a mild electric pulse to their feet or affected the ability to associate the mild annoyance of the pulse with the place where it happened — an indication that they had acquired a threat memory.
Sung Han Richard Palmiter
Sun Han and Richard Palmiter study brain circuits underlying behavior.Sun Han and Richard Palmiter
The researchers first looked to see what effect the switching “off” the CGRP cells in the PBN had on the mice’s response to the electronic pulse. They found mice still had the reflexive withdrawl responses to the electric pulse but did not try to escape, as normal mice would. “It was as though they felt the pulse, but did not care,” Han said.
This behavior of the CGRP-silenced mice suggested that the PBN cells transmit the emotional component of pain to the amygdala. The fact that the mice also did not freeze to a standstill when they were returned to the tray — a sign they associated the tray with the pulses — suggesting that the affective component was needed to create a threat memory.
To tease out what was going on, Han used a technique called optogenetics to directly activate the CGRP cells without administering any stimulus to the mouse’s foot. He found that when he activated the CGRP neurons in the PBN alone, the mice froze and developed a threat memory as normal mice would to such an experience. This suggested the PBN cells generate the affective component of a signal needed for the mouse to show an immediate defensive response as well as generate a threat memory.
The second set of cells in the circuit, the cells in the amygdala that also appear to be essential in forming threat memory. After these cells were blocked, the mice did not try to escape to a pulse as normal mice would. They also failed to acquire a threat memory. But activating the cells caused the mice to do both. “What this means,” Han explains, “is that by activating just these amygdala cells alone, it is possible to create a false memory of an experience that never happened,” Han said.
“The findings,” said Palmiter, “indicate that the PBN-amygdala circuit is the affective — the emotional — pain pathway required to create the memories we need to avoid the same situations in the future. The discovery of this circuit suggests that it maybe possible to treat painful conditions, particularly those that often have a significant emotional component, with drugs that alter the function of the CGRP neuron signaling.”
This work was supported by the Howard Hughes Medical Institute.
Tagged with: pain management, neurobiology
http://hsnewsbeat.washington.edu/story/how-do-we-learn-stay-away-potential-harm
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