WORLD
JOURNAL OF ACUPUNCTURE-MOXIBUSTION
Vol.10 No.2,
June, 2000
Experimental Research
Thermolytic
Effect of Moxibustion and
Its Relation to
Acupoint Receptors
*
This study was supported by a grant from the National Natural
Science Foundation of China
by
Xian Maoquan(先茂全)
Dong Quansheng(董泉声)
Zhang
Suhua(张素华)
Dong Xinmin( 董素民)
(Dept.
of Physiology, Institute of Acupuncture, Moxibustion and
Meridians,
Sichuan
Academy of TCM and Pharmacology, Chengdu 610031, China)
Abstract
In the present paper, the effect of moxibustion stimulation
(by using a computer automatically-controlled condensed light) of
Dazhui (GV 14) etc. on auricular temperature changes was observed
in the rabbit after intravenous injection of endotoxin. Changes of
rabbit's auricular temperature were sampled and recorded by using
a thermistor-thermometer (connected with a computer) before and
after moxibustion stimulation. Results indicated that moxibustion
making the skin temperature reach to 48oC could inhibit
the endotoxin-induced lowering reaction of auricular temperature,
while moxibustion making the skin temperature of 40oC
had no this effect. It revealed that higher-skin-temperature
moxibustion had a thermolytic effect on body-fever, which had a
close relation mainly with polymodal receptors rather than with
temperature receptor. It also demonstrated that endotoxin-induced
changes of auricular temperature could be used as an index for
evaluating the thermolytic effect of moxibustion.
Key
Words Moxibustion therapy Thermolytic effect
Acupoints Polymodal Receptors
In
clinical practice of traditional Chinese medicine (TCM),
moxibustion treatment of heat-syndrome has a long history. Li Yan,
a physician in the 16th century, said in his book Elementary
Medicine that “in treatment of patients with excess-syndrome,
moxibustion therapy is used to guide the accumulated heat to go
out of the body surface", indicating a practicability of
moxibustion for treatment of heat-syndrome. There have been a few
reports about experimental studies on moxibustion therapy for
reducing fever[1-3].
But, the available data are still limited. For this reason, in the
former study[4],
we adopted a thermistor-thermometer (connected with a computer) to
sample and record changes of ear and rectal temperature after
intravenous injection of endotoxin. Results confirmed the
reliability of this method for observing the thermolytic eff ect
of moxibustion. In the present paper, we compared the effect of
moxibustion on endotoxin-induced fever when the thermal receptors
(WR) and polymodal receptors (PR) were excited with skin
temperature of 40oC and 48oC, respectively;
analyzed the relationship between the thermolytic effect of
moxibustion and its afferent system and further verified the
advisability of the index, endotoxin-induced auricular temperature
changes, for evaluating the thermolytic effect.
Materials
and Methods
1.
Animals and Grouping
30
healthy and adult New Zealand rabbits (15 males and 15 females)
were randomly and evenly divided into 5 groups: A: normal saline
control group (intravenous injection of 1ml of normal saline); B:
endotoxin group (intravenous injection of 25 Eμ endotoxin);
C: endotoxin +40oC moxibustion group; D: endotoxin +48oC
moxibustion group; and E: normal 40oC
and 48oC moxibustion group.
2.
Determination of Ear, Rectal and Room Temperature
The
animals were taken to the laboratory and hanged in an animal stand
with the chest carried by a piece of canvas and the four limbs
suspending in the air. A multi-meridian thermistor-thermometer was
used to detect the auricular, rectal and room temperature and the
temperature signals were input into a micro-computer and sampled
once every 2.5 min. The room temperature was kept constant between
29 and 30oC in the former 4 groups and between 27 and
28oC in the last group. For same one rabbit, the room
temperature was tried to be kept in ±0.1oC. The
temperature of the control ear was from 35 to 36oC. The
data were saved in the computer and printed.
3.
Endotoxin and Its Usage
Bacillus
cili endotoxin (E, coli, O111 and B4) produced by Shanghai
Institute of Biological Products were used in this study. Every
ampoule contained 700 Eμ endotoxin, diluted into 25 Eμ/ml
with normal saline to be injected into rabbits' ear marginal vein.
All the glass and metal appliances were heated under 2 50oC
for 30 min in an oven for destroying the pyrogen.
4.
Acupoints and Moxibustion
Acupoints,
Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9) and Baihui (GV 20,
located between the processes of the 7th lumbar and the 1st sacral
vertebrae) were selected. Hairs around the acupoint area were cut.
Moxibustion, replaced by a beam of condensed light controlled
automatically using a computer[5],
and with the skin temperature being kept 40 or 48oC,
was given over the acupoint immediately after intravenous
injection of endotoxin. Every acupoint was radiated for 15 min
every time, 1 hour all together. The neck part prior to Dazhui (GV
14) was fixed to a board with a half round hole. The fissure was
filled with heat insulator to prevent ear from heat radiation. The
height, thickness and width of the board were 40, 1.5 and 26 cm
respectively. The observation lasted for 6 hours after intra
venous injection of endotoxin.
5.
Indexes for Observation
1) Curve
of auricular temperature changes induced by endotoxin: Comparison
of the auricular temperature changing curves after injection of
endotoxin and endotox in plus moxibustion was made to evaluate the
therapeutic effect of moxibustion qualitatively.
2)
Quantitative indexes: a) Latency of endotoxin-induced decrease of
auricular temperature: the duration from the time of end of
injection to the beginning of lowering of auricular temperature.
b) Amplitude of temperature lowering: the difference between
control temperature before endotoxin injection and the lowed
temperature after injection. c) Index of temperature lowering:
represented by the area which was encircled by
temperature-lowering period, low temperature period and
temperature rising period, and the control value of ear
temperature was use d as the standard, and calculated according to
geometric multiplication in division and division. The hour-degree
was used as the unit.
6.
Statistical Analysis
All the
data were expressed by mean values ±SD and analyzed using student
T-test.
Results
1. Effect
of Intravenous Injection of Normal Saline on Ear Temperature
The
rabbits' auricular temperature kept relatively stable during 6
hours' observation except for temporary and slight fluctuation in
some rabbits when the ear skin was pricked by syringe. The
temperature fluctuated between±1oC , shown in the
attached figure. While the rectal temperature fluctuation was very
small, between 39.1±0.2oC (control value) and
39.2±0.1oC.
2. Effect
of Intravenous Injection of Endotoxin on Auricular Temperature
After
intravenous injection of endotoxin (25 Eμ), the auricular
temperature changes contained lowering stage, low-temperature
stage, rising stage and supernormal stage (shown in Figure 1 and
Table 1). The supernormal stage was referred t o the period of
increase of ear temperature or that of temperature being higher
than the control value, lasted for a longer period time and was
related to higher body temperature. The data of the 3 indexes of 6
rabbits were shown in Table 2.
Table 1.
Time-course (min) of Changes of Ear Temperature (T)
after
Intravenous Injection of Endotoxin (M±SD, n=6)
|
| Latency
stage |
T-lowering stage |
Low-T stage |
T-rising
stage |
(1)-(4) |
Supernormal stage |
|
| 17.1±
2.9 |
27.5±
5.2 |
24.2±
3.8 |
43.0±
8.4 |
111.8±
3.7 |
Didn't turn to the
control level 6 hr after injection |
|
Table 2.
Effect of Moxibustion on Endotoxin-induced
Changes of
Auricular Temper ature (M±SD)
|
| Groups |
Cases |
Latency(min) |
T-lowering
amplitude (oC) |
Index for T-lowering (hr-d) |
|
| A:
Endotoxin |
6 |
17.1±2.9 |
4.7±0.6 |
4.34±0.96 |
| B:
Endotoxin + moxibustion of 40oC |
6 |
18.3±2.6 |
5.1±1.5 |
4.07±1.2 |
|
C:
Endotoxin + moxibustion of 48oC
|
3 |
28.3±8.8* |
2.8±0.5** |
1.87±0.28** |
|
*P<0.05,
**P<0.01 compared with group A
The
rectal temperature changes after intravenous injection of
endotoxin included monophase fever stage, latency, rising stage,
peak stage and lowering stage ( Figure 1).
3. Effect
of Moxibustion of 40oC on Ear Temperature after
Injection of Endotoxin
After
moxibustion making skin temperature reach to 40oC, the
situations of auricular temperature changes in 6 rabbits were
similar to those mentioned above. The time-courses of the
former 4 stages were 18.3±2.7, 28.7±7.9, 22.5±4.7, and 38.3±7.4
respectively, with the total value being 107.9±2.2, which were
close to those of endotoxin group. The mean values of the 3
indexes were shown in Table 2. There was no any significant
difference between endotoxin group and endotox in + moxibustion
with 40oC skin temperature group, indicating no
significant influence of moxibustion with skin temperature of 40oC
on endotoxin-induced changes of ear temperature.
4. Effect
of Moxibustion of 48oC on Auricular Temperature
after Injection of Endotoxin
After
intravenous injection of endotoxin, the changes of auricular
temperature in 3 of the 6 rabbits were suppressed completely by
moxibustion making skin temperature reach to 48oC.
Among the 3 cases, the auricular temperature kept stable in 2
cases during rotary moxibustion, showing a relative balance
between the moxibustion action and endotoxin-indced
decrease of ear temperature; in the rest 1 case, the auricular
temperature began to increase when moxibustion lasted 7.5 min, and
increased by 2.5-3oC (Fig. 2), suggesting a stronger
influence of moxibustion on auricular temperature changes. In the
above 3 rabbits, the long term supernormal stage still existed
(Fig. 2)
Figure 1.
Changes of auricular and rectal temperature after intravenous
injection of endotoxin
AT:
auricular temperature; RT: rectal temperature; ET: environmental
temperature; ↓: intravenous injection of endotoxin; A, B,
C, and D represent the latency , T-lowering stage, low T
stage, T rising stage and supernormal stage respectively. I, II,
II and IV represent the latency, T-rising stage, peak stage
and T- lowering stage of rectal T changes respectively.
Fig. 2.
Influence of moxibustion under skin temperature of 48oC
on endotoxin- induced changes of auricular temperature (I)-complete antagonism
AT:
auricular temperature; RT: rectal temperature; ET: environmental
temperature; ↓: intravenous injection of endotoxin; —:
the duration of moxibustion under skin temperature of 48oC,
every 15 min for moxibustion of Dazhui (GV 14), Shenz hu (GV 12),
Zhiyang (GV 9) and Baihui (GV 20) respectively, 1 hr altogether.
In other
3 rabbits, a partially inhibitory phenomenon appeared, manifested
as a longer latency, smaller amplitude of temperature decrease and
temperature lowering index (Fig. 3 and Table 2).
Comparison
between moxibustion (48oC) +endotoxin and
endotoxin groups in the auricular temperature showed a
significant or a very significant difference ( P<0.05 or 0.01).
After moxibustion making skin temperature reach to 48oC,
the auricular temperature presented increase, lowering first and
rising later and relative steadiness separately in each one of the
3 rabbits. After stopping moxibustion, a long-term
supernormal stage was found in every animal. In 4 cases, the
auricular temperature did not turn to the control level till the
end of observation in spite of recovery of the rectal temperature
(Fig. 2).
Fig. 3.
Effect of moxibustion under skin temperature of 48oC on endotoxin-induced changes of auricular temperature (II)-complete antagonism
AT:
auricular temperature; RT: rectal temperature; ET: environmental
temperature; ↓: intravenous injection of endotoxin; —:
the duration of moxibustion under skin temperature of 48oC,
each 15 min for moxibustion of Dazhui (GV 14), Shenzhu (GV 12),
Zhiyang (GV 9) and Baihui (GV 20) respectively, 1 hr altogether.
5. Effect
of Moxibustion of 40oC and 48oC
on the Auricular Temperature in Normal Rabbits
The
auricular temperature of 6 rabbits in normal control group was
between 33 and 35oC. During moxibustion making
skin temperature reach to 48oC, the auricular
temperature increased by 1oC, 3oC
and 4oC respectively in 1, 2 and 3 rabbits. In
all the 6 animals, a poststimulation effect was found. In
other 4 rabbits, after moxibustion making skin temperature reach
to 40oC, the auricular temperature increased by
1oC, 1.5oC and 2oC
in 1, 1 case and 2 cases separately (Fig. 4).
Fig. 4.
Influence of moxibustion under skin temperature of 40oC
and 48oC on endotoxin-induced changes of
auricular temperature
AT:
auricular temperature; RT: rectal temperature; ET: environmental
temperature; ↓: beginning of moxibustion;---and —: duration of moxibustion under skin temperature of 40oC and 48oC
separately, each 1 hr for the two kinds of moxibustion, i.e.
every 15 min for moxibustion of Dazhui (GV 14), Shenzhu (GV 12),
Zhiyang (GV 9) and Baihui(GV 20) respectively.
Discussion
The
results showed that moxibustion of acupoints at 48oC
of skin temperature could significantly inhibit or antagonize
endotoxin-induced lowering action of auricular
temperature, indicating a facilitating action of moxibustion
therapy on heat dissipation from body surface. It provides an
experimental evidence for thermolytic pathway of moxibustion.
But, moxibustion making skin temperature reach to 40oC
had no this effect, indicating a close relation between
thermolytic effect and moxibustion temperature (stimulating
strength). These results are identified with those referred in
our former paper[3],
in which moxibustion making skin temperature reach to 47oC
had a significant antipyretic effect. According to the past
research work, the temperatures most sensitive for WR were fro m
40 to 42oC [7],
and the threshold temperature for PR was 46.7oC[8].
Therefore, it is advisable that the interrelation between the
effect of moxibustion and these two types of receptors can be
differentiated by taking moxibustion of 40oC and
47-48oC skin temperature[3].
The results of the present paper show that the antipyretic effect
results mainly from PR reaction rather than WR. There also exists
an identical interrelation between the conclusion and the
material basis of acupoints for reducing fever . The thermolytic
effect and fever abatement after moxibustion are in fact two reactions of cause-result relation and the results
correspond to the objective regularity. In this paper, the
auricular temperature change (following intravenous injection of
endotoxin) is used as the index for evaluating the effect of moxibustion, which is advisable from the relevance, sensitivity,
accuracy and the unity between the results or conclusion and the
thermolytic effect of moxibustion.
WR is an
important perceptual apparatus receiving temperature stimulation
of the surrounding environment changes. It is activated when the
skin temperature goes up to 30oC, and increases
in firing rate along with the increase of skin temperature. When
the skin temperature rises to 40oC, WR presents
the best sensitive state. In this paper, moxibustion making skin
temperature reach to 40oC could cause t he
auricular temperature to increase to a certain degree in normal
rabbits, suggesting that WR excitement could produce a
thermolytic effect in the normal organ ism. But moxibustion of 40oC
had no any marked effect on endotoxin-induced changes of
auricular temperature, this may be associated with pyrogen-induced
alternation of the functional state of the regulation center of
the body temperature. Some physiological workers reported in
1960s that pyrogen could suppress the discharge rate of thermal
sensitive neurons of the pre-optic area anterior hypothalamus (POAH) or lower the sensitivity of these neurons to local
temperature changes. Hence, it is reasonable that after injection
of endotoxin, the thermal sensitive neurons decrease their
sensitivity to thermal changes or loss their reaction capability.
After all, the acupoint area of moxibustion is small, if the stimulated area is enlarged to a certain degree, it is not
impossible that a heat dissipation reaction is induced via a
comprehensive process of enhancement of functional activity of
thermal sensitive neurons in the central nervous system.
PR is a
pain perceptive apparatus and is sensitive to noxious heat,
mechanical and chemical stimulation. Its responding threshold for
temperature is higher, above 40oC. We found
that the threshold of 36 PR in the rabbits' limbs with hair was
46.7±0.5oC (M±SE)[8]
. In some research, in which the analgesic effect was produced by
heat pain stimulation or moxibustion pain stimulation, the pain
receptors involved should be PR[13-15].
But, our results showing PR receptors are involved in the process
of thermolytic effect and those mentioned in the past and the
present papers are reported for the first time in the world.
Thus, it is foreseeable that moxibustion treatment and PR have a
wide range of relation, which is an important issue to be worthy
of concern.
The
thermolytic effect of PR in the organism with fever contains two
aspects: A) moxibustion of skin temperature of 40oC
can raise the auricular temperature in normal rabbits or those
with fever caused by endotoxin and in the latency period. This
effect of moxibustion and endotoxin-induced lowering of
auricular temperature are opposite, suggesting an antagonistic
effect of moxibustion on endotoxin. This effect of moxibustion is
similar to that of stronger electroacupuncture[6],
belonging to the
category of somato-sympathetic reflex[16]. In consideration
of the intrinsic relation of input information and the defensive
areas including hypothalamus, mesencephalon, ventrolateral area
of medulla oblongata, etc., and involvement of sympathetic
efferent activity, their relation needs to be studied further. B)
No matter whether the auricular temperature rises or not in the
rabbit with fever caused by intravenous injection of endotoxin and
in the latency period, moxibustion making skin temperature reach
to 48oC
could produce a significant inhibitory effect on endotoxin-induced
lowering of auricular temperature. Pyrogen can change the
processes of heat production and dissipation to generate fever by
influencing functional activities of thermal sensitive neurons in
POAH. F or this reason, it is possible that the inputs of
moxibustion stimulation by PR converge to the thermal sensitive
neurons in the central nervous system to generate an opposite
action against the effect of endotoxin. Up to now, the connection
process in the central nervous system, the exact effect of the
afferent information on thermal sensitive neurons and the
involvement of the sympathetic nerve system remain unknown but are
the important links of moxibustion treatment. It is thus worthy
of further study.
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