항 Serotonin약물이 electroacupuncture의 진통효과에 미치는 영향

Abstract

[영문]

[한글]

침술의 진통효과가 specific opiate antagonist인 naloxone에 의해 소실됨은 침술이 중

추신경내의 endogenous opiate system과 연관되어 진통작용을 나타낼 가능성이 상당히 높

다. 특히 endogenous opiate system은 morphine의 주작용부위로 알려진 중뇌의 periaqued

uctal gray(PAG) 부위에 상당량 존재하며 PAG가 활성화 될 경우 연수의 nucleus raphe ma

gnus(NRM)가 활성화되며 NRM으로부터 척수로의 raphe-spinal serotonergic신경로의 통하

여 말초로부터 대뇌피질까지의 통각전달을 척수후각에서 차단함으로써 진통효과를 나타낸

다고 알려졌다. 따라서 항 serotonin약물을 이용하여 raphe-spinal serotonergic신경로의

작용을 억제시킬때 electroacupuncture의 진통효과에 미치는 영향을 관찰함으로써 침술

이 뇌간내의 endogenous opiate system을 활성화시키는지를 구명코져 본 실험을 시행하였

다.

체중 2.0∼3.5kg정도의 성숙한 고양이를 실험동물로 하였으며 항 serotonin 약물로는 p

-chlorophenylalanine(p-CPA)과 5,6-dihydroxytryptamine(5,6-DHT)을 사용하였는데 p-CPA

는 복강내로, 5,6-DHT는 측뇌실에 주사하였다. 또한 생리식염수를 복강 및 측뇌실에 주사

한 고양이를 대조군으로 하였다. 모든 실험동물은 실험시 제뇌시켜 사용하였으며 동통반

사로 확인된 굴근반사를 동통의 지표로 하였다. 굴근반사는 고양이 하지의 sural nerve를

자극할 때 posterior biceps femoris근에 분포된 운동신경에서 유발되는 compound actio

n potential을 기록함으로써 얻을 수 있었다. 본 실험에서는 electroacupuncture대신 굴

근반사를 기록한 동측하지의 common peroneal nerve를 선택하여 20V의 강도, 2 msec dura

tion 및 2 Hz의 빈도로 60분간 자극한후 굴근반사에 미치는 영향을 관찰하였고 아울러 mo

rphine이 굴근반사에 미치는 영향도 조사하여 다음과 같은 곁과를 얻었다.

1. 생리식염수를 투여한 대조군의 경우 말초신경의 전기자극은 굴근반사를 현저히 감소

시켜 진통효과를 보였으며 naloxone에 의하여 그 효과는 소실되었다.

2. 항 serotonin 약물투여군에 있어서 말초신경 자극 후 굴근반사는 감소하여 진통효과

를 보였지만 대조군에 비해 진통효과는 현저히 억제되었다. 이 경우도 감소된 굴근반사는

역시 naloxone에 의하여 원상으로 회복되었다.

3. 항 serotonin 약물투여군에 있어서 morphine의 진통효과는 현저히 억제되었다.

이상의 결과로 보아 말초신경자극 또는 electroacupuncture의 진통작용은 중추신경내의

endogenous opiate system을 활성화시킴으로써 나타나며 그 부위는 주로 뇌간일 것으로

생각된다.

Effect of Anti-Serotonin Drugs on the Analgesia Induced by Electroacupuncture

Kwang Se Paik

Department of Medical Science The Graduate School, Yonsei University

(Directed by Professor Doo Hee Kang, M.D., Ph. D.)

Acupuncture has a very long history as a means for relieving pain in man.

Recently, the most exciting findings were reported that 1) analgesic effect of

acupuncture can be reversed by naloxone, specific opiate antagonist, 2) presence of

morphine-like substances, endorphin and enkephalin, in mammalian central nervous

system was demonstrated. These findings suggest the possibility of involvement of

endogenous opoids in acupuncture analgesia.

It has been known that the midbrain periaqueductal gray(PAG) which is believeth

to be a major locus of morphine and stimulation-produced analgesia. contains

moderately high levels of endogenous opoids. When the PAG neurons are activated by

microinjection of morphine and electrical stimulation, it excite the medullary

nucleus raphe magnus (NRM) which inhibit spinal dorsal horn neurons implicated in

pain transmission through the descending raphe-spinal pathway. There is some

evidence that serotonin is involved in this action, because NRM efferents are

serotonergic. If endogenous opiate system in brainstem is involved in acupuncture

analgesia, it should be possible to demonstrate suppression of analgesic effect of

acupuncture when the raphe-spinal serotonergic system is inactivated by

anti-serotonin drugs.

Present study, therefore, was performed to test this possibility. Experiments

were conducted in anemic decerebrate cats treated with anti-serotonin drugs,

p-chlorophenylalanine (p-CPA) and 5,6-dihydroxytryptamine (5,6-DHT). p-CPA,300

mg/kg was administered intraperitoneally, two or three days before the experiment

and 5,6-DHT, 100㎍ was injected into lateral cerebral ventricle, five or six days

prior to the experiment. Control cats were given volumetrically equivalent amounts

of normal saline, either intraperitoneally or intraventricularly. To test the

effect of electroacupuncture and morphine on the pain reaction, the flexion reflex

was used as an index of pain. Previous studies from our laboratory have shown that

electroacupuncture and peripheral nerve stimulation produced identical analgesic

effect. Based on these findings, peripheral nerve stimulation was used a

simiulation of electroacupuncture. The flexion reflex was elicited by stimulating

the sural nerve and recorded as a compound action potential from the nerve

innervated to the posterior biceps femoris muscle in the ipsilateral hindlimb. The

common peroneal nerve in the same hindlimb was selected as the site of peripheral

nerve stimulation. For the stimulation of common peroneal nerve, a stimulus of 20 V

intensity, 2 msec duration and 2Hz frequency was applied for 60 min.

The results are summarized as follows:

1. In control cats, electrical stimulation of the common peroneal nerve markedly

depressed the flexion reflex which was reversed completely by systemic application

of naloxone hrdrochloride(0.05 mg/kg).

2. In experimental cats treated with anti-serotonin drugs. common peroneal nerve

stimulation induced far less depression of the flexion reflex compared to the

control cats. This diminished depressive effect was also reversed by naloxone.

3. Depressive effect of morphine(0.5-2.0 mg/kg) on the flexion reflex was

dramatically inhibited in anti-serotonin drugs treated cats.

These results suggest that: 1) peripheral nerve stimulation induces analgesic

effect by activation of the raphe-spinal descending serotonergic system, 2) the

raphe-spinal descending serotonergic system activation is finally controlled by

endogenous opiate system, mainly in brainstem.