Peripheral TRPV1 channels mediate the antihypertensive effect of warm needle acupuncture = 온침 자극의 TRPV1 활성을 통한 항고혈압 효과 및 말초 기전 규명|RISS 상세보기

다국어 초록 (Multilingual Abstract)

Acupuncture, a traditional Korean medicine, has been used to treat various diseases. Acupuncture treatment is performed using various methods, including heat stimulation, electrical stimulation and mechanical stimulation. Among these methods, warm needle acupuncture involves applying heat stimulation by burning moxa on the top of acupuncture needles in addition to the physical stimulation. It is used to treat various conditions, but the mechanism of warm needle acupuncture is still unclear. In this study, I developed a temperature-controllable warm needle acupuncture instrument (WAI) and investigated the peripheral mechanisms underlying antihypertensive effects in a rat model of immobilization-induced hypertension. First, I measured the temperature of traditional warm needle acupuncture and examined the correlation between warm needle acupuncture and TRPV channels using a TRPV antagonist. The results showed that traditional warm needle acupuncture suppressed the development of hypertension, which was blocked by the pretreatment with a TRPV antagonists. Secondly, the antihypertensive effects of 48 ºC WAI stimulation were similar to those of traditional warm needle acupuncture and the administration of a TRPV1 agonist capsaicin at the PC-6. In contrast, the antihypertensive effect by WAI was blocked by pretreating the PC-6 with TRPV1 antagonist capsazepine. WAI stimulation at PC-6 increased the numbers of dorsal root ganglia double-stained with TRPV1 and CGRP-positive neurons. Chemical ablation of small afferent nerve fibers (C-fibers) by perineural injection of a mixture of Qx-314 and capsaicin into the median nerve prevented the antihypertensive effect of WAI. Additionally, pretreatment of PC-6 with RTX ablated the antihypertensive effect of WAI stimulation. These findings suggest that warm needle acupuncture at PC-6 attenuates the development of hypertension through the activation of peripheral TRPV1.
Key words: acupuncture, warm needle acupuncture, PC-6, hypertension, TRPV1
* A thesis submitted to committee of the University of Science and Technology in a partial fulfillment of the requirement for the degree of Doctor of Engineering in February 2024

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국문 초록 (Abstract)

침술은 전통 한국의학에서 다양한 질병을 치료하는데 사용되어왔 습니다. 경혈 자극은 열 자극, 전기 자극, 물리 자극 등 다양한 방법이 있다. 그 중에서 열을 통하여 경혈을 자극하는 방법 중 하나인 온침은 침의 물리적 자극과 침병위에 부착한 애주를 태워 발생한 열을 더하여 경혈을 자극하는 방법으로, 임상에서 다양한 질환 치료 및 연구에서 널리 사용되고 있지만 온침 자극의 말초기전은 아직 불분명하다. 이 연구에서 온도 조절이 가능한 온침기(WAI)를 개발하고 온침을 통해 부동으로 유도된 고혈압 동물 모델에서 항고혈압 효과의 말초 기 전을 연구하였습니다. 첫째, 온침의 온도를 측정하고 TRPV채널 길항제를 사용하여 온침 자극과 TRPV 채널 간의 상관관계를 관찰한 결과 내관혈 온침 자극이 고혈압 발생을 억제하였으며 내관혈에 TRPV 길항제 전처리는 온침의 항고혈압 효과를 차단한다. 둘째, 내관혈 48 ºC 온침기 자극은 전통 온 침과 유사하게 항고혈압 효과가 발생하였으며 TRPV1 작용제인 capsaicin을 내관혈에 주사하면 온침과 유사한 효과가 발생하였다. 반 면에 온침기에 의한 항고혈압 효과는 TRPV1 차단제인 capsazepine 의 내관혈에 전처리에 의해 차단되었습니다. 내관혈 온침기 자극은 TRPV1 및 CGRP 이중 염색된 DRG 뉴런 발현을 증가시켰습니다. QX-314와 capsaicin의 혼합물을 정중 신경에 주입하여 C-섬유를 특 이적으로 차단하면 온침기의 항고혈압 효과가 발생하지 않았습니다. 또한 resiniferatoxin의 내관혈 전처리 하여 말초 감각신경의 차단은 온침기의 효과를 차단하였습니다. 본 연구 결과는 내관혈의 온침 자극이 말초의 TRPV1 수용체를 활 성화하고 정중신경의 C-fiber를 통해 중추신경내로 전달되어 항고혈압 효과를 유발하는 것으로 나타났다.
주요단어(Key words): 경혈, 온침, 내관혈, 고혈압, TRPV1, 정중신경

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침술은 전통 한국의학에서 다양한 질병을 치료하는데 사용되어왔 습니다. 경혈 자극은 열 자극, 전기 자극, 물리 자극 등 다양한 방법이 있다. 그 중에서 열을 통하여 경혈을 자극하는 방법 ...

목차 (Table of Contents)

1. Introduction 1
Chapter. 1. 4
2. Materials and Methods 5
2.1. Animals and ethics statement· 5
2.2. Chemicals 5

1. Introduction 1
Chapter. 1. 4
2. Materials and Methods 5
2.1. Animals and ethics statement· 5
2.2. Chemicals 5
2.3.
Measurement of the temperature delivered to the needle by
warm needle acupuncture
5
2.4. Warm needle acupuncture at PC-6 6
2.5. Pharmacological blockade of TRPV at PC-6· 7
2.6.
Measurement of blood pressure and immobilization-induced
hypertension rat model
7
2.7. Data analysis 8
3. Results 9
3.1. Measurement of temperatures generated by warm needle
acupuncture
9
3.2. Effect of traditional warm needle acupuncture at PC-6 on
systolic blood pressure
11
3.3. Mediation of PC-6 TRPV channels in the anti-hypertensive
effect of warm needle acupuncture
13
Chapter. 2. 15
4. Materials and Methods 16
4.1. Animals 16
4.2. Chemicals 16
4.3. Development of the warm needle acupuncture instrument
and acupuncture treatment
17
4.4. Measurement of the temperature delivered to the needle by
the warm needle acupuncture instrument ·
18
4.5. Pharmacological blockade of TRPV1 channels and small
afferent nerve fibers
19
4.6. Pharmacological blockade of C-fibers in the median nerve·· 19
4.7. Immobilization-induced hypertension and measurement of
systolic blood pressure
20
4.8. Immunohistochemical analysis of dorsal root ganglia
(DRGs) and skin
20
4.9. Data analysis 22
5. Results 23
5.1. Temperature measurement at the acupuncture needle tip of
warm needle acupuncture instrument
23
5.2. Effect of warm needle acupuncture at PC-6 on the anti-
hypertensive effect in an IMH rat model
25
5.3. Mediation of median nerve C-fibers in the anti-hypertensive
effect of WAI·
28
5.4. Involvement of peripheral TRPV1 in the antihypertensive
effect of WAI at PC-6
30
5.5. Activation of small afferent nerve fibers by WAI
stimulation at PC-6
33
5.6. Inhibition of the PC-6 stimulation antihypertensive effect by
chemical ablating TRPV1 with RTX·
35
6. Discussion· 38
Reference · 45
This paper is based on the study titled 'Attenuation of
immobilization stress-induced hypertension by temperature-
controllable warm needle acupuncture in rats and the peripheral
neural mechanisms', which was published in Frontiers in
Neurology in 2023

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