Volume 1, Special Edition | Current Japanese Acupuncture and Moxibustion 2010

– Somatosensory stimuli including acupuncture
modulate blood flow via the autonomic
reflexes –excitation of the cholinergic nerve fibers originating inShinjiro Yamaguchi
Acupuncture & Massage Research Information Center

extracellular

Somatosensory stimuli including acupuncture elicit
reflex autonomic responses that affect functions in the
cardiovascular system and other organs (Sato et al.,1997). An analysis of the neural mechanisms of
inducedautonomicreflex

responses(somato-autonomic reflex) is essential in developing ascientific understanding of the mechanism underlying
the effects of acupuncture therapy.
This article reviews recent studies performed
by Japanese researchers regarding vascular reflex
responses induced by somatosensory stimuli including
acupuncture.

basalisofMeynert;

acetylcholine

(Ach)

NBM)

releases

incortex,

theresulting in an increase in cortical blood flow,

Uchida et al. (2000) demonstrated the effect ofacupuncture-like stimulation for 1 min to various skinareas on cortical blood flow measured using a laser
Doppler flowmeter in anesthetized rats. The results
clearly showed that the increase in cerebral blood flow,
independent of systemic blood pressure, elicited byacupuncture stimulation is a reflex response in which
the afferent nerve pathway is composed of somaticgroups III and IV afferent nerves, and efferent nerve
pathway includes intrinsic cholinergic vasodilators
As proven by Hotta et al. (2002), ischemia-induced

There has been great progress in research on
cardiovascular responses induced by natural somatic
stimuli using anesthetized animals in order toeliminate emotional factors. It has been shown that
sympathetic rather than parasympathetic nerves playa major role in somato-cardiovascular reflexes. In
somato-cardiovascular responses, the brain stem plays
an important role as the reflex center. Although spinal
segmental stimulation elicits spinal reflex components,
such components are usually depressed by descending
inhibitory pathways from the brain under a central
system

Acupuncture-like stimulation

originating in the NBM.

Characteristics of somato-cardiovascular reflex

nervousnucleus

independent of metabolic vasodilation.

Introduction

somaticallythe magnocellular nucleus of the basal forebrain (the(CNS)

intactcondition.

delayed death of rat cortical neurons can be protectedby preventing a blood flow decrease in widespreadcortices via NBM-originating vasodilative activation.
Therefore, it appears that continuous acupuncture
stimulation prevents cerebral infarction though its
vasodilative effect in the cerebral cortex.
Effects of somatosensory stimuli on peripheral blood flow

Sympathetic reflex
The effect of electro-acupuncture stimulation (EAS)
to a hindpaw (0.1-10 mA, 20 Hz, 30 s) on muscle bloodflow measured by laser Doppler flowmetry and on

Whenmean arterial pressure (MAP) was investigated byanesthetized rats are in a CNS-intact condition,

Noguchi et al. (1999). EAS to a hindpaw at a strength

somatic afferent stimulation of limbs is particularly

sufficient to excite group III and IV afferent fibers, caneffective in producing cardiovascular responses. Limb

produce a reflex increase and/or decrease in muscle

somatic afferent fibers seem to have specific synaptic

blood flow. They clarified that two types of responses

connections to the CNS.

are induced passively by pressor response via aEffects of somatosensory stimuli on cerebral blood flowsplanchnic sympathetic activity, and/or directly by an

Background

activation of muscle sympathetic nerves.

Recent studies by Sato and colleagues (Sato andAre small vessels such as arterioles affected bySato, 1992) have shown that cortical cerebral blood

somatic afferent stimulation including EAS? The

flow is regulated by intracranial nerves. Particularly,authors' group (Takagi et al., 2005) investigated theThe Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

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Volume 1, Special Edition | Current Japanese Acupuncture and Moxibustion 2010

effects of EAS of the hindpaw and the dorsal Th13-L1
level area on the mesenteric microhemodynamics inanesthetized rats using an intravital microscope
system. We observed that the hindpaw EAS evoked
intensity-dependent pressor responses and an increasein blood flow velocity, measured by the dual-sensor
method developed by the authors, in mesentericprecapillary arterioles, while the dorsal EAS evoked
depressor responses and a decrease in blood flow
velocity.

Occasional

butnotablereflexvasoconstrictions in the mesenteric terminal arteriole
by EAS of both sites were observable on the image
under

the

intravital

microscope.

These

vasoconstrictive responses were not affected by theadministration of an alpha-adrenergic blocker. Ourstudy

directlychanges

atdemonstrated

thelevelofthat

hemodynamic

precapillaryarterioles

accompanying EAS either on the hindpaw or the back,mainly depend on the changes of systemic arterialpressure regardless of stimulation current intensities.
Moreover, the results in our study suggest somereceptors other than alpha-adrenergic receptor might
be involved in the mechanism of EAS-induced
vasoconstriction in the mesenteric arteriole.
Satoetal.

(1996)

demonstrated

that

acupuncture-like simulation induced catecholamine
secretion from the adrenal medulla via activation of
the adrenal sympathetic nerves in anesthetized rats.
To examine whether such somatically induced
catecholamine is effective on microvascular tone, theauthors investigated the effects of 10 min (3 mA) ofFigure 1: Effects of adrenalectomy on precapillaryarteriolar constriction (a) and pressor response (b)induced by electrical stimulation (ES) of the back skin
(3 mA, 20 Hz, intermittent, 10 min) in anesthetizedrats. The open bar shows the responses to ES in theintact rats. The closed bar shows the responses
induced by ES in the bilateral adrenalectomized rats.
*p<0.05, **p<0.01; statistical significant is obtained
between the pre-stimulus values and the values at 4-5min (a) and 2-3 min (b) after onset of the stimulus.
+p<0.05, ++p<0.01; statistical significance is expressed
between responses in two groups. (Modified from
Yamaguchi et al. 2002)

Nitric oxide
It is well known that nitric oxide (NO) is aphysiologically active substance producing variousfunctions. NO, especially, plays an important role invasodilation in arterioles.

electrical stimulation of the dorsal skin area (Th5-12In the knee joint, blood flow is known to belevel) on the mesenteric arterioles in anesthetized rats

modulated mainly by sympathetic postganglionicusing an intravital microscope system (Yamaguchi etfibers, but recently the release or induction of NOal., 2002). Electrical stimulation of the skin for 10 min

synthesis in response to electrical stimulation has also

evoked a decrease in the diameter of arterioles. In thebeen suggested. Therefore, direct observation of theadrenalectomized group, electrical stimulation of the

microcirculation is needed to further understand theskin for 10 min elicited a slight increase in themechanism by which blood flow is regulated bydiameter (Fig. 1). It is therefore suggested that thesomatic afferent stimulation. The author's groupconstriction of the mesenteric precapillary arterioles(Loaiza et al., 2002) observed the effects of EAS (5 mA,induced by the stimulation for 10 min was mediated by

0.5 ms, 5 Hz, 30 min) to the vastus medialis muscle on

humoral adrenaline and noradrenaline released by

MAP and the knee joint microcirculation using asomato-adrenal medullary reflex.

real-time confocal laser-scanning microscope system.

16The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 1, Special Edition | Current Japanese Acupuncture and Moxibustion 2010

Significant and persistent increases in arteriolar
diameter and MAP, were observed after EAS to themuscle. EAS to the vastus medialis in the presence ofN(omega)-nitro-L-arginine methyl ester (L-NAME)
produced a strong decrease in diameter of the knee
joint arterioles under the baseline with a simultaneous
increase in MAP. EAS to the skin did not producechanges in arteriolar diameter while a slight increaseinMAP overthebaseline

occurred

after thestimulaitons. EAS to the muscle after neuromuscular
blockade did not produce significant changes indiameter, while an increase in MAP was still observed,
which suggests that muscle contraction is required toproduce vasodilatation (Fig. 2). These responses
suggestthatadynamicbalancebetweentheautonomic nervous system and the release of NO is theprimary mechanism mediating the EAS effects onknee joint microcirculation.

Figure 2: Summarized data on the changes in joint
capsule arteriolar diameter in anesthetized rats. Thevalues were registered at 30 min of observation in thecontrol (non-stimulated) and L-NAME group and at
the end of the stimulus in the elactro-acupuncture
stimulation (EAS) to vastus medialis muscle, EAS tothe muscle + L-NAME, EAS to the muscle + relaxantand EAS to skin groups. Statistical significance isindicated as *p<0.05, **p<0.01 when compared to thepre-stimulus values, and +p<0.05, ++p<0.01 whencompared to the control group. (Modified from Loaiza
et al. 2002)

Axon reflex
When an axon reflex is induced by cutaneous

stimulation, the excited afferent terminal releases
vasodilative
substances,such
ascalcitonin
gene-related peptide (CGRP).
The contribution of CGRP to antidromic vasodilationof skeletal muscle blood flow following electricalstimulation of muscle afferent was investigated by Satoand colleagues using anesthetized rats. They concluded
that antidromic vasodilation in skeletal muscles
following stimulation of unmyelinated C afferents in
dorsal roots is independent of systemic blood pressure
and is mediated essentially by CGRP. They describedthat this CGRP-related antidromic vasodilation isprobably important in the clinical improvement ofskeletal muscle blood flow caused by physical therapy
such as acupuncture.
The authors assessed by measurement of two
different hemodynamic parameters: muscle blood flowusing a laser Doppler flowmeter; and the changes indiameter of the muscle arterioles observed directly using
an intravital microscope system in order to examine theeffects of electrical stimulation (5 V, 20 Hz, 30 s) to thesaphenous nerve on microcirculation of the gracilis
muscle in anesthetized rats (Loaiza et al., 2002). We
found that ipsilateral nerve ES produced vasodilative
responses in the muscle accompanied by increases inmuscle blood flow independently of the sympathetic
nerve activity. Furthermore, CGRP was found to be
directly involved in the reflex neural regulation of themuscle
microcirculation,whichsuggests
theparticipation of an axon reflex mechanism (Fig.3).

Figure 3: Effect of ipsilateral electrical stimulation(ES) of the saphenous nerve on gracillis muscle
arteriolar diameter in the absence and presence of

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

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Volume 1, Special Edition | Current Japanese Acupuncture and Moxibustion 2010

topical CGRP8-37. Representative photographs of two
different arterioles, observed pre- and post-stimulus
are illustrated. (Modified from Loaiza et al. 2002)
Conclusions
1. The cerebral blood flow response induced byacupuncture-like stimulation of a forepaw in rats,
independent of MAP, is a reflex response whoseafferents are group III and IV somatic afferent
fibers, and whose efferents are cholinergic fibers
originating in the NBM.
2. The somatically induced peripheral circulatory
regulation system consists of three types ofmechanisms as follows.
(1) Hemodynamics in the region of interest isaffected by systemic circulatory changes inducedby the somatic afferent stimulation.
(2) The observed blood vessels are directly affectedby activating the autonomic efferent nerve fibers
including nonadrenergic, noncholinergic fiberthat can release NO.
(3) Vasodilative response induced by the CGRP
through activating the primary afferent fibers(axon reflex).
These physiological findings may support theeffectiveness of acupuncture therapy on patients withcirculatory disturbances.
References
1. Sato A, Sato Y, Schmidt RF: The impact ofsomatosensory input on autonomic functions. Rev
Physiol Biochem Pharmacol 130: 1-328, 1997
2. Sato A, Sato Y: Regulation of regional cerebral
blood flow by cholinergic fibers originating in thebasal forebrain. Neurosci Res 14: 242-274, 199218

3. Uchida S, Kagitani F, Suzuki A, Aikawa Y: Effect ofacupuncture-like stimulation on cortical cerebral
blood flow in anesthetized rats., Jpn J Physiol 50:495-507, 2000
4. Hotta H, Uchida S, Kagitani F: Effects ofstimulating the nucleus basalis of Meynert onblood flow and delayed neuronal death following
transient ischemia in the rat cerebral cortex. Jpn JPhysiol 52: 383-393, 2002
5. Noguchi E, Ohsawa H, Kobayashi S, Shimura M,
Uchida S, Sato Y: The effect of electro-acupuncture
stimulation on the muscle blood flow of thehindlimb in anesthetized rats, J Auton Nerv Syst
75: 78-86, 1999
6. Takagi K, Yamaguchi S, Ito M, Ohshima N: Effectsof electroacupuncture stimulation applied to limb
andbackonmesentericmicrovascularhemodynamics. Jpn J Physiol 55: 191-203, 2005.
Epub 2005 Sep 7
7. Yamaguchi S, Ito M, Ohshima N: Effects ofelectrical stimulation of the dorsal skin on
systemicandmesentericmicrovascularhemodynamics in anesthetized rats. Jpn J Physiol
52: 257-65, 2002
8. Loaiza LA, Yamaguchi S, Ito M, Ohshima N:
Electro-acupuncture
stimulationtomuscleafferents in anesthetized rats modulates the bloodflow to the knee joint through autonomic reflexes
and nitric oxide. Auton Neurosci. 97: 103-9, 2002
9. Sato A, Sato Y, Shimura M, Uchida S: Calcitonin
gene-related peptide produces skeletal muscle
vasodilation following antidromic stimulation of
unmyelinated afferents in the dorsal root in rats.
Neurosci Lett 283: 137-140, 2000.
10. Loaiza LA, Yamaguchi S, Ito M, Ohshima N:
Vasodilatation of muscle microvessels induced bysomatic afferent stimulation is mediated bycalcitonin gene-related peptide release in the rat.
Neurosci Lett 333: 136-40, 2002

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