실험적 말초신경 손상후 신경증을 일으킨 흰쥐에서 통증반응에 미치는 TENS의 효과/허철령

Abstract

[한글]

말초신경 손상후 나타나는 만성통증은 작열성 통증(causalgia), 기계적 이질통(mechanical allodynia), 지각과민(hyperesthesia), 온도 이질통(thermal allodynia) 등의 증상을 나타내게 된다. 그러나 이런 말초신경 손상후 발생한 만성통증 증후군에 관한 정확한 기

전이나 치료방법에 대해서는 아직 연구가 미진한 실정이다. 따라서 본 실험에서는 횐쥐를 대상으로 신경병적 만성통증(neurepathic pain)을 유발하기 위해 제 5 및 제 6 요 척수신경을 묶어 말초신경을 손상시켜 기계적 이질통을 유발하고, 그 매의 비복신경의 입력을 받는 척수후각세포에서 활성도 변화를 전기생리학적 기록법을 이용하여 관찰하였다. 말초신경 손상후 변화된 척수후각세포의 특성 변화를 관찰하고, 또한 임상에서 진통목적으로 흔히 사용하고 있는 transcutaneous electrical nerve stimulation(TENS)이 실험적 신

경병적 만성통증에도 진통효과를 보이는 지를 알아 보기 위해 요 척수신경을 노출만 했던 실험대조군 및 수술조작을 가하지 않았던 정상군과 비교, 관찰한 결과 다음과 같은 결론을 얻었다.

1. 한 쪽 제 5 및 제 6 요 척수신경을 묶어 신경병적 만성통증 모델로 삼은 실험군에서는 수술후 24시간이 지나면서 수술한 쪽의 발이 정상군에서는 무해한 von Frey filament나 brush자극에 대해 실험대조군에 비해 예민하게 반응하였으며 시간이 경과함에 따라 그

반응은 증가하여 한 달 이상 지속함을 볼 수 있었다.

2. 비복신경 자극에 의해 활성화되는 척수후각세포는 실험군에서 실험대조군에 비해 상대적으로 WDR세포는 증가하고 HT세포는 감소하는 경향을 보였다. 또한 실험군에서는 정상에서 나타나지 않는 WDR-LT 형태를 보이는 세포가 나타남을 관찰할 수 있었다.

3. 실험군에서는 비복신경 자극에 의해 활성화되는 척수후각세포의 피부말초수용야의 범위가 실험대조군에 비해 널게 변화된 것을 볼 수 있었다.

4. 비복신경 자극에 의해 활성화되는 척수후각세포는 실험군에서 자발적 활성도가 나오는 세포의 수 및 그 발사빈도가 실험대조군보다 증가하였으나 통계적 의의는 없었으며, brush나 Squeeze에 대한 반응은 정상군에 비해 의의 있는 증가를 보였다.

5. TENS를 시행한 결과, 실험대조군에서는 squeeze에 대한 반응만이 감소되었으나 실험군에서는 brush와 squeeze에 대한 반응 모두가 의의 있는 감소를 보임으로써 양군간의 TENS효과의 차이를 보였다.

이상의 결과로 보아 실험적으로 말초신경 손상을 만들어 신경증을 유발하였을 때 기계적 이질통이 나타나고, 통증 전달과 연관된 척수후각세포의 특성이 일부 변화됨을 알 수 있었다. 또한 진통목적으로 사용되는 TENS는 이러한 기계적 이질통도 억제할 수 있을 것으로 생각된다.

Effect of TENS in a model for neuropathic pain in rots

Chul Ryung Hur

Department of Medical Science, The Graduate School Yonsei University

(Directed by Professor Kwang Se Paik)

The chronic pain syndrome after peripheral nerve injury, is often characterized

by such symptoms and signs as spontaneous burning sensation, mechanical allodynia,

hyperesthesia, and drystrophic change in the peripheral tissue. The precise

mechanisms and therapeutic trials about them have been yet unknown. The purpose of

this study was to investigate the characteristics of dorsal horn neurons with sural

input and the effect of TENS in a neuropathic pain model group, comparing with sham

operation group and control group.

The neuropathic pain which was made by unilateral ligations of L5 and L6 spinal

nerves was developed within 24 ∼48 hours after surgery. Most rats in model group

showed a marked increase in frequency of paw withdrawal response to innocuous

mechanical stimuli with von Frey filament. In the neuropathic Pain model, dorsal

horn neurons activated by stimulation of aural nerve had more C inputs compared to

sham operation group. In model group the proportion of WDR cell was larger, and

that of HT cell was smaller than that of sham operation group. The receptive fields

of the neurons were expanded by peripheral nerve injury. The dorsal horn neurons in

model group exhibited the tendency to have higher spontaneous activities. Innocuous

mechanical stimuli evoked mean discharge frequency of 20 Hz in model group and only

6 H? in control group. The noxious stimuli such as squeeze also evoked more

discharges in model group than control group.

TENS was applied with the intensity of 1∼5mA and the frequency of 27Hz for 1 min

on the affected side thigh to examine the effect of TENS on the neuropathic pain

model. In sham operation group TENS showed differential inhibition that did not

reduce the responses by an innocuous stimuli such as brushing but reduced the

responses by squeeze. But in the model group, TENS could reduce not only the

responses by squeeze but also those by brushing. These results suggest that TENS

could alleviate mechanical allodynia in the neuropathic pain.

[영문]

The chronic pain syndrome after peripheral nerve injury, is often characterized by such symptoms and signs as spontaneous burning sensation, mechanical allodynia, hyperesthesia, and drystrophic change in the peripheral tissue. The precise mechanisms and therapeutic trials about them have been yet unknown. The purpose of this study was to investigate the characteristics of dorsal horn neurons with sural input and the effect of TENS in a neuropathic pain model group, comparing with sham operation group and control group.

The neuropathic pain which was made by unilateral ligations of L5 and L6 spinal nerves was developed within 24 ∼48 hours after surgery. Most rats in model group showed a marked increase in frequency of paw withdrawal response to innocuous mechanical stimuli with von Frey filament. In the neuropathic Pain model, dorsal horn neurons activated by stimulation of aural nerve had more C inputs compared to sham operation group. In model group the proportion of WDR cell was larger, and that of HT cell was smaller than that of sham operation group. The receptive fields

of the neurons were expanded by peripheral nerve injury. The dorsal horn neurons in model group exhibited the tendency to have higher spontaneous activities. Innocuous mechanical stimuli evoked mean discharge frequency of 20 Hz in model group and only

6 H? in control group. The noxious stimuli such as squeeze also evoked more discharges in model group than control group.

TENS was applied with the intensity of 1∼5mA and the frequency of 27Hz for 1 min on the affected side thigh to examine the effect of TENS on the neuropathic pain model. In sham operation group TENS showed differential inhibition that did not reduce the responses by an innocuous stimuli such as brushing but reduced the responses by squeeze. But in the model group, TENS could reduce not only the responses by squeeze but also those by brushing. These results suggest that TENS could alleviate mechanical allodynia in the neuropathic pain.