CHAPTER CONTENTS

6
Acupuncture points and meridians 70
Acupuncture points 70
Meridians 71 Mechanisms of
Spinal segmental mechanisms 72 acupuncture
Heterosegmental acupuncture 74
The serotonergic system 75 David Bowsher
The noradrenergic system 77
Diffuse noxious inhibitory controls (DNIC) 77

Conclusion 79

Acupuncture has been used for more than two

thousand years in China and Japan; the earliest
literary reference is in The Yellow Emperor’s
book of internal medicine, dating from the second
or third century BC. Acupuncture reached Japan
in the sixth century of the Christian era, and was
introduced into Europe by ten Rhijne (1683), who
had learnt about it in Japan. As a therapy, it
spread very slowly in Europe. The first European
and American publications on acupuncture treat-
ment appeared in the early nineteenth century
(Bache 1826, Berlioz 1816, Churchill 1821, Cloquet
1826). Although acupuncture was used to a
considerable extent in conventional medical
practice in Europe throughout the nineteenth
century, attracting such mainstream giants as
Osler, its use gradually died out.
While some pioneers such as Felix Mann
in the UK and a number of practitioners in France
were using acupuncture extensively from the
middle of the present century, it was really only
in the 1970s that acupuncture captured the public
interest and came to be widely practised. Films of
acupuncture anaesthesia for operative surgery
coming out of China following President Nixon’s
visit in 1972 fired the public imagination.
Acupuncture received full scholarly treatment in
the West in the magisterial treatise of Lu &
Needham (1980).
In addition to classical acupuncture, a number
of variations exist. Notable among these are
Ryodoraku (Hyodo 1990, Nakatani & Yamashita
1977, Yoshio 1969) and auricular acupuncture,
introduced in France by Nogier (1972). Auricular
69
 70 THEORY AND BASIC SCIENCE

acupuncture has been further studied by blocked by local anaesthesia, acupuncture is

Johnson et al (1991). ineffective in the territory supplied by that nerve
Eventually, acupuncture in Western medicine prove that the acupuncture effect is conducted
came to be mainly used for pain relief (Mann et along nerves (Chiang et al 1973). From the
al 1973), and much later for the treatment of standpoint of modern neurophysiology, this is
postoperative nausea and vomiting (Dundee et perhaps the most important and fundamental
al 1986). The present chapter will be concerned piece of information on acupuncture.
entirely with an attempt to explain acupuncture
in relation to pain relief.
Acupuncture points
The fact that not all subjects respond to acu-
puncture appears to present great difficulties to Acupuncture is said to be effective only at
some medical scientists. Acupuncturists divide certain points on the body surface, known as
the population into responders and non- acupuncture points. In fact, comparison with an
responders. Many animals may also be classed anatomical atlas (e.g. Williams et al 1989) shows
as non-responders, for instance, some rats show that many of these points correspond with the
no prolongation of the tail-flick response latency points at which small nerve bundles penetrate
following acupuncture (Takeshige et al, 1980a). the fascia; Chan (1984) cites two Chinese studies
As will be more fully discussed below, showing that 309 acupuncture points are
acupuncture analgesia in people and animals situated on or very close to nerves, while 286 are
is reversed or abolished by naloxone under on or very close to major blood vessels, which
most conditions, showing that its mechanism are of course surrounded by small nerve bundles
is opioidergic. In human subjects in whom (nervi vasorum).
pain was relieved by acupuncture, an increase That sympathetic nerves may also be involved
in cerebrospinal fluid (CSF) β-endorphin level was first demonstrated by Goulden (1921), who
was noted (Clement-Jones et al 1980). Although showed that acupuncture points along the
CSF met-enkephalin levels did not appear to sciatic nerve and its branches have a lower
be changed in this study, it has recently been impedance than does the surrounding skin.
observed in the rat (Bing et al 1991) that Yoshio (1969) has shown that Ryodoraku points
met-enkephalin-like material is in fact released have similar properties. Many acupuncture
in the substance of the spinal cord itself by points are of course deep within the skin.
acupuncture-like stimulation. Recently, Takeshige Melzack, Stillwell & Fox (1977) have shown that
et al (1990) have shown that non-responsive many of them correlate closely with Travell’s
animals (as measured by non-prolongation of ‘trigger points’ (Travell & Simons 1983), while
tail-flick latency) can be rendered responsive by Liu, Varela & Oswald (1977) have demonstrated
treatment with D-phenylalanine, which inhibits that other points correspond to the motor points
the enzyme that degrades met-enkephalin. of muscles, where the nerves enter or leave
Attribution of response failure in rats to differ- them. The Hoku point (LI-4), of course, has long
ences in enzyme mechanisms is reminiscent of been known to correspond to the superficial
the observation that humans who fail to respond branch of the radial nerve in the anatomical
to morphine for the relief of nociceptive pain ‘snuff-box’; but the foregoing demonstrates that
appear to have differences in the enzymatic all acupuncture points examined correspond to
mechanisms for its glucuronidation (Bowsher small nerve bundles, either cutaneous (purely
1993). sensory, or sensory plus sympathetic), vascular
(mixed sympathetic and sensory), or muscular
(mixed sensory and motor).
ACUPUNCTURE POINTS AND
While segmental acupuncture is undoubtedly
MERIDIANS
the most effective form for pain relief, acupuncture
Experiments showing that, when a nerve is at distant points has been found empirically also
 MECHANISMS OF ACUPUNCTURE 71

to be effective. In order to demonstrate this, to areas of skin affected by postherpetic neuralgia

ancient practitioners drew up illustrations in (PHN). In 1990, Nurmikko & Bowsher showed
which ‘points’ were joined by lines that in Western that, in areas of skin affected by PHN, pinprick
practice are called ‘meridians’; the intention was sensation is usually absent.
to show that stimulation at a particular point may Thus it may be regarded as established beyond
have an effect elsewhere on the meridian, or in a reasonable doubt that Aδ sensory units must be
viscus after which the meridian was named. stimulated in order to produce the acupuncture
This raises two distinct issues: effect. It should, however be mentioned that, in
a number of recent papers, Kawakita and his
1. Are the ‘points’ fixed entities?
colleagues (e.g. Kawakita 1991) have suggested
2. How are ‘meridians’ to be interpreted in
that C polymodal nociceptors should also be
terms of modern anatomical and
considered as a physiological substrate of the
physiological knowledge?
acupuncture effect. While it cannot be excluded
If in fact the points are small nerve bundles, that stimulation of such sensory units may
then of course their precise position will vary contribute in some measure to the acupuncture
from individual to individual in accordance effect, both the parameters of stimulation and the
with normal biological variation. perceived sensation following needle stimulation
Most practitioners of acupuncture find that appear to us to militate strongly against the
effective points, when needled, give rise to a possibility that C polymodal nociceptors are the
subjective feeling of warmth in the patient and sole, or even the principal, substrate. Indeed,
are often revealed to the therapist as a red flare earlier work on suppression of the jaw-opening
in the skin. This of course is the axon reflex, reflex in rats by both electroacupuncture and
brought about by stimulation of C and A delta selective Aδ stimulation (Kawakita & Funakoshi
(Aδ) fibres. Its absence merely indicates that the 1982) strongly support the notion that Aδ fibres
needle has not hit nerve fibres, and therefore has are principally concerned in the acupuncture
not been inserted into an effective ‘point’. effect. It may also be added that, unlike the
While a needle may mechanically stimulate situation with respect to Aδ fibres (see below),
nerve fibres of many types, it is most important there are no known central connections of
to establish which peripheral nerve fibre type is C fibres that could explain inhibition of (other)
responsible for the acupuncture effect. It was C fibre input. Table 6.1 correlates the different
suggested some time ago (Bowsher 1976) that sensory fibre types with their physiological
Aδ fibres were involved, because the adequate functions and with their role in acupuncture
stimulus is needleprick, while the response analgesia and the TCM phenomenon ‘De Qi’.
frequency is 2–3 Hz; these are both properties of Note that, whilst superficial acupuncture involves
Aδ primary afferents. This theoretical hypothesis Aδ nerve fibres, deep (muscle) acupuncture also
has been confirmed practically in two different stimulates Aδ fibres. The ‘soreness’ component
ways. First, it has been demonstrated beyond of acupuncture is the result of stimulating
doubt, by microneurographic stimulation in C fibres.
conscious human volunteers, that stimulation of
Aδ fibres gives rise to a pricking sensation, like
Meridians
that of being stimulated with a needle. Secondly,
Wang et al (1985) showed that Aδ fibres from The second issue—that of the ‘correct’ acupuncture
muscle conveyed various sensations which points and their relation to meridians—is more
Chiang et al (1973) had shown were essential for complex. Some effect may be produced at any
the acupuncture effect. point where a nerve bundle containing Aδ fibres
An interesting corollary arises in a disease is stimulated, owing to central effects from
state: Levine, Gormley & Fields (1976) found descending inhibitory controls (DNIC) (Bing,
that acupuncture was ineffective when applied Villanueva & Le Bars 1991). However, powerful
 72 THEORY AND BASIC SCIENCE

Table 6.1 Neurophysiology of needling (after Thompson 1994)

Sensory Sensory Diameter Velocity Function Role in Role in

Fibre Fibre µm m/s (mph) analgesia* De Qi†
ABC type I–IV type

Aα 1a 15–20 70–120 Annulo-spiral muscle spindles [length]

1b (155–270) Golgi tendon organ [load]
Aβ II 5–12 30–70 Touch
(70–155)
Aγ II 3–6 15–30 Flower spray muscle spindles [length] + Numbness
(35–70)
Aδ III 2–5 12–30 Pinprick sensation (= first or fast pain), + Aching,
(25–70) cold, pressure distension,
heaviness
C IV 0.4–1.2 0.5–2 Aching pain (= second or slow pain), itch, heat Soreness
(1–4.5)

References: Guyton 1991, Ganong 1993. * Bowsher 1988, Pomeranz & Paley 1979, Toda & Ichioka 1978, † Wang et al 1985,
Thompson 1994.

effects are produced only following stimulation demonstrated that sweat production in humans
at particular non-segmental points on a meridian. is reduced by acupuncture. Interestingly, it is
As pertinently suggested by Baldry (1993), it is frequently observed that patients sweat profusely
likely that, at least in part, we are dealing with during treatment with acupuncture.
the as yet ill-understood mechanisms of referred It has recently been suggested (Iguchi & Sawai
effects, as studied by such workers as Kellgren 1993, Yamada, Hoshino & Watari 1993) that at
and Lewis before World War II (see Baldry 1993 least some meridians may correspond to lymphatic
for details). While such explanations appear to channels. Like blood vessels, lymphatics are
depend entirely on interactions within the somatic accompanied by fine nerve fibres, as evidenced,
nervous system, attention should also be given for example, by the pain felt following untreated
to pathways travelling in the autonomic nervous hand infection that travels up the arm to the
system and interactions between the autonomic axillary lymph glands.
and somatic nervous systems. There is a
considerable body of evidence implicating the
sympathetic nervous system in acupuncture
SPINAL SEGMENTAL MECHANISMS
effects: the first report (Matsumoto & Hayes Acupuncture analgesia is blocked or reversed by
1973) demonstrated a fall in blood pressure and naloxone (Cheng & Pomeranz 1980, Mayer,
intestinal vasodilation following electroacu- Price & Rafii 1977, Sjölund & Eriksson 1979).
puncture in rabbits. More recently, transient Melzack, Stillwell & Fox (1977) have identified
skin vasoconstriction followed by a longer- many of Travell’s trigger points with
lasting warming effect has been demonstrated in acupuncture points. It is therefore of great
normal human volunteers following both interest that pain relief by trigger point injection
manual and electrical acupuncture stimulation with bupivicaine is also reversed by naloxone
(Ernst & Lee 1985), again revealing autonomic (Fine, Milano & Hare 1988). Han, Ding & Fan
effects elicited by acupuncture. In fact, as early (1986) have also shown that intracerebro-
as 1977, Nakatani & Yamashita had drawn ventricular or intrathecal injection of chole-
attention to the fact that Ryodoraku acupuncture cystokinin octapeptide (CCK-8), which is an
points are in areas of skin containing sweat endogenous opioid antagonist, antagonizes
glands, and modern Ryodoraku theory attributes analgesia produced both by morphine and by
the heterosegmental effects of acupuncture to electroacupuncture in the rat. All these lines of
interactions between sympathetic and somatic evidence clearly point to an opioidergic mechanism
nervous systems. Ogata et al (1993) have of action for acupuncture. Table 6.2 summarizes
 MECHANISMS OF ACUPUNCTURE 73

Table 6.2 Neuropharmacology: the role of some the role of some neurotransmitters in acupuncture
neurotransmitters in acupuncture analgesia (after Han 1984)
analgesia and compares the action of each on the
Substance Brain Spinal brain and spinal cord.
(PAG) cord It therefore behoves us to examine the intra-
Monoamines
spinal connections of Aδ primary afferent
5-hydroxytryptamine (5-HT) + + terminals (Fig. 6.1). Kumazawa & Perl (1978)
noradrenaline (NAD) – + showed that Aδ primary afferents in the primate
Peptides
met-enkephalin + +
end principally in the most superficial zone
dynorphin A & B 0 + (lamina I) and neck (lamina V) of the dorsal
β-endorphin + 0 horn of the spinal grey matter. In the region of
substance P (SP) + –
cholecystokinin octapeptide (CCK-8) – –
the large superficial cord cells, there are other
Amino-acids very small cells, called ‘stalked cells’ demon-
γ-amino butyric acid (GABA) – 0 strated in the cat by Bennett et al (1982) and in
Key: + potentiation, – antagonism, 0 no effect,
humans by Abdel-Maguid & Bowsher (1984);
PAG periaqueductal grey. these suppress activity in the subjacent cells of
the substantia gelatinosa (SG), on which the
small unmyelinated ‘pain fibres’ end (Sugiura,

Spinorecticular
Excitatory

tract
Inhibitory

Skin -
St SG WDR
ENK +
+
C
Polymodal
Painful scar nociceptor

Spinothalamic tract
Aδ

High-threshold
mechanoreceptor

Acupuncture

Figure 6.1 Mechanism of segmental acupuncture. The C primary afferent polymodal nociceptor projects to substantia
gelatinosa (SG) cells in the superficial dorsal horn; these generate further impulses that pass to, or perhaps disinhibit, wide
dynamic range (WDR) (or convergent) cells whose axons pass up to the brain in the spinoreticular tract where they are
eventually interpreted as painful.
The Aδ primary afferent pinprick receptors project both to marginal cells (M), which project up to the brain in the
spinothalamic tract carrying information about pinprick that will become conscious, and to enkephalinergic stalked cells (St),
which can release enkephalins (ENK) that inhibit SG cells, thus preventing information generated by noxious stimulation being
transmitted further. (After Thompson & Filshie 1993, derived from Bowsher 1992.)
 74 THEORY AND BASIC SCIENCE

Table 6.3 Effect of stimulation frequency (from Thompson 1994)

Frequency Low (2–5 Hz) High (20–200 Hz)

Technique Manual or electrical Electrical: electroacupuncture

Type High intensity/low frequency Low intensity/high frequency
Predominant met-enkephalin Dynorphins
pharmacology β-endorphin 5-HT + NAD
Naloxone Blocks effect Unaffected

Lee & Perl 1986). It has been shown that stalked HETEROSEGMENTAL
cells do not react to frequencies of stimulation ACUPUNCTURE
above about 3 Hz (Bowsher et al 1968, Harper &
Lawson 1985), which is the optimal frequency at There is no doubt that, in clinical practice,
which acupuncture analgesia stimulation is acupuncture at certain points can relieve pain in
performed. The stalked cells inhibit SG cells by distant regions supplied by nerves from totally
releasing on to them the inhibitory opioid trans- different segments. It is therefore necessary to
mitter enkephalin (Ruda, Coffield & Dubner 1984). consider the physiological mechanisms that may
Stalked cells also receive a direct input from Aδ underlie these phenomena. To do this, two
pinprick fibres (Gobel et al 1980). It has recently distinct, but sometimes anatomically intermingled,
been directly demonstrated (Bing et al 1991) that ascending pathways must be examined, as well
acupuncture-like stimulation in the rat induces as the descending pathways that may inhibit the
release of enkephalin-like material in the spinal upward transmission of impulses generated by
cord. Very recently, Sjölund and his colleagues noxious stimulation.
(personal communication) and Hashimoto & In the spinal cord WDR, or convergent, cells
Aikawa (1993) have shown that manual (Giesler et al 1976, Willis & Coggeshall 1978)
acupuncture in the rat induces inhibition in respond to most stimuli in a graded manner;
the wide dynamic range (WDR) cells, which noxious stimulation in the periphery causes them
project up to the brain, conveying impulses to fire at highest frequency. All types of peri-
that will be consciously interpreted as painful. pheral afferent can therefore excite WDR cells,
WDR cells are influenced by SG cells (Fig. 6.1), after relaying through variable numbers of
thus completing the circuit. Table 6.3 illus- interneurons in the dorsal horn of the spinal
trates the effect of stimulation frequency on grey matter; WDR cells do not receive mono-
the predominant pharmacological response of synaptic connections from primary afferents.
the primary afferent input (Aβ and Aδ nerve Some WDR cells are to be found in lamina V, in
fibres). the neck of the spinal dorsal horn, but most of
Thus, the intraspinal terminals of primary them are to be found in the deeper layers
afferent Aδ (pinprick) fibres branch to supply (laminae VII and VIII) of the intermediate spinal
the large Waldeyer cells in the marginal layer grey matter. These cells send their axons to the
(lamina I) and the enkephalinergic stalked opposite side of the spinal cord, where they ascend
cells at the border between laminae I and II (SG) in the anterolateral funiculus as the spinothalamic
of the dorsal horn. Since Aδ primary afferent and spinoreticular tracts (Kuru 1949, Bowsher
fibres stimulate the stalked cells, and these 1957). Essentially, the spinoreticular pathway
in turn enkephalinergically inhibit the SG cells, carries information generated by the stimulation
we have an adequate explanation of the mech- of nociceptors to the reticular formation, the
anism for segmental acupuncture interrupting intralaminar thalamus and the hypothalamus
the pain pathway from C fibres to the WDR (Fig. 6.2) (Burstein, Cliffer & Giesler 1987); the
cells. spinothalamic tract, on the other hand, carries
 MECHANISMS OF ACUPUNCTURE 75

information generated by thermal and pinprick Investigations by Mayer & Liebeskind (1974)
receptors to the ventroposterior thalamus (Willis showed that a descending inhibitory pathway
& Coggeshall 1978, Willis 1985). Many of the passing down from the caudoventral part of the
cells projecting into the spinothalamic tract lie in PAG to the spinal cord was responsible for the
the marginal zone (lamina I), and are activated inhibition of neurons with ascending axons that
by Aδ pinprick receptors. It is thus of great carry messages generated by painful stimuli in
interest that the heterosegmental acupuncture the periphery (Fig. 6.2). There is evidence that
effect in the rabbit is abolished by section of the there is a somatotopic organization within this
anterolateral funiculus, but not by destruction of part of the PAG (Soper & Melzack 1982); this
other long ascending spinal cord pathways (Chen might explain why heterosegmental acupuncture
et al, 1975). We must therefore enquire what effects cannot be obtained from any acupuncture
collateral connections of the spinothalamic point, but only from particular points that are
pathway may be responsible for the activation, not necessarily within the dermatome in which
directly or indirectly, of descending inhibitory it is desired to obtain pain relief.
pathways. In addition, physiological research The pathway descending from the PAG, whose
(Takeshige 1992, Tsai, Chen & Lin 1993) has transmitter substance is probably neurotensin
shown that two transmitter systems—serotonergic (Beitz 1982), relays in the nucleus raphe magnus
and noradrenergic—are involved (Figs 6.2, 6.3), (NRM) of the medulla oblongata. From the NRM,
and Tsai, Chen & Lin (1993) have recently shown fibres whose transmitter substance is mainly
that central adrenergic, as well as serotonergic, serotonin (5-hydroxytryptamine, 5-HT) descend
neurons are excited by acupuncture stimulation. in the dorsolateral funiculus (DLF) of the spinal
We shall therefore consider heterosegmental cord to terminate directly on the stalked
acupuncture effects under these two physio- enkephalin-containing interneurons in the spinal
pharmacological headings and finally mention a dorsal horn (Glazer & Basbaum 1984), which
third system that may contribute to the were discussed above. There are also serotonin-
acupuncture effect. containing nerve terminals ending freely in the
superficial part of the spinal cord grey matter
(Hammond, Tyle & Yaksh 1985, Leranth,
The serotonergic system Maxwell & Verhofstad 1984, Maxwell, Leranth
It has been known for some time that spino- & Verhofstad 1983). This could explain the
thalamic collaterals reach the midbrain peri- ‘hormonal’ or generalized type of acupuncture
aqueductal grey matter (PAG) in the primate effect, as opposed to the point-to-point or neural
(Mantyh 1982a), and Zhang et al (1990) have type. Increased serotonin levels in mast cells and
recently shown that these axons originate from platelets have been reported following acu-
cells in lamina I. puncture (Souvannakitti et al 1993, Wu & Deng
It was in 1964 that Tsou & Jang demonstrated 1993). Both these latter phenomena might (but
that the PAG is the most effective spot in the very cautiously) be considered an explanation of
whole nervous system for the abolition of pain by those acupuncture effects that outlast direct
microinjection of morphine. As the PAG was synaptic inhibition.
known not to send messages upwards to the Finally, as mentioned earlier, the PAG receives
cerebral cortex so that these messages did not fibres containing the naturally occurring
become conscious, this amazing finding was morphine-like substance β-endorphin (Bloom et
conveniently overlooked by most researchers. al 1978); these fibres descend from the arcuate
However, in 1968 Reynolds showed that painless region of the hypothalamus (Mantyh 1982b), a
surgery could be carried out in the rat during primitive but essential part of the forebrain
electrical stimulation of PAG, and this led to concerned not only with regulation of bodily
intensive research on possible mechanisms. functions but also with emotion. In humans, the
 76 THEORY AND BASIC SCIENCE

Somatotopic projection to sensory cortex

Cingulate gyrus

Prefrontal
cortex

Ventral
posterior
Diffuse cortical lateral
Fronto-arcuate nucleus
connection projection

Medial intralaminar nucleus Thalamus

Arcuate
Descending N.
inhibitory
pathway
OP
Hypothalamus
PAG

Multisynaptic system
RF RF

nRM

5HT
Dorsolateral funiculus

Excitatory

Spinoreticular
Inhibitory
tract
Skin

Polymodal
nociceptor -
Painful scar St SG WDR
ENK +
+
C
Spinothalamic tract

Aδ

High-threshold
mechanoreceptor

Figure 6.2 Serotonergic mechanism of acupuncture. Pinprick information is carried up from marginal cells (M) (see also Fig.
6.1) to the ventroposterior lateral thalamic nucleus, whence it is projected to the cortex and becomes conscious; but in the
midbrain these axons give off a collateral branch to the periaqueductal grey matter (PAG). The PAG projects down to the
nucleus raphe magnus (NRM) in the midline of the medulla oblongata, and this in turn sends serotonergic (5-HT) fibres to the
stalked cells (St). The latter inhibit substantia gelatinosa cells (SG) by an enkephalinergic mechanism (ENK), and so prevent
noxious information arriving in C primary afferent nociceptors from being transmitted to wide dynamic range (WDR) cells deep
in the spinal grey matter, which send their axons up to the brain (reticular formation, RF). OP = opioid peptides.
The PAG is also influenced by opioid endorphinergic fibres descending from the arcuate nucleus in the hypothalamus, and
the hypothalamus in turn receives projections from the prefrontal cortex. (After Thompson & Filshie 1993; derived from
Bowsher 1992 see Fig. 11.3 p 188.)
 MECHANISMS OF ACUPUNCTURE 77

hypothalamus is under the control of the stimulation, because the inhibitory effects of
prefrontal cortex, a region whose blood flow is direct stimulation of this structure are antagonized
increased by painful stimuli (Lassen, Ingvar & by phentolamine. However, they point out that
Skinhöj 1978, Tsubokawa et al 1981). It is because the paragigantocellular reticular nucleus does
the pathway from hypothalamus to PAG is not itself contain any noradrenergic cells; nor
endorphin-containing that pain relief in humans does it project directly to the spinal cord. It must
can be obtained by stimulating electrodes im- therefore relay to a noradrenergic structure
planted in the PAG or in the periventricular before directly influencing spinal activity. This
region anterior to it (Richardson 1982) in which may be the locus coeruleus, or some other
the hypothalamo-PAG fibres run. This morphine- noradrenergic lower brainstem cell group whose
like pain relief is reversed by naloxone (Hosobuchi, axons project into the spinal cord. For example,
Adams & Linchitz 1977, Richardson & Akil 1977). in the primate, Carlton et al (1991) have identi-
Within the PAG itself, there are inhibitory fied noradrenergic cells in the C1 area of the
interneurons that are themselves inhibited by medulla and pontomedullary junction whose
the long-descending β-endorphin-containing axons descend on the edge of the lateral white
hypothalamo-PAG fibres, which accounts for the funiculus of the spinal cord to the superficial
release of activity in the PAG–NRM pathway dorsal horn, the intermediate and the circum-
and thus inhibition in the spinal cord via the canalicular grey matter. Takeshige (1992) believes
inhibitory NRM–spinal pathway. that the descending noradrenergic system, like
Modulation of pain perception through the that descending from PAG, is ultimately con-
emotional or psychic state of the individual may trolled from the prefrontal cortex and the
depend on the projection from the prefrontal arcuate nucleus of the hypothalamus.
cortex through the hypothalamus to the PAG.
Because the type of acupuncture effect
descending through PAG is eventually sero-
Diffuse noxious inhibitory controls
tonergic, it is antagonized by methysergide Diffuse noxious inhibitory controls (DNIC)
(Takeshige, Sato & Komugi 1980). (Fig. 6.3) is the name given to a powerful pain-
suppressing system described by Le Bars (Le
Bars, Dickenson & Besson 1979) and his collab-
The noradrenergic system orators. Much research by this group has shown
In the cat and monkey, lamina I of the spinal that DNIC is an opioidergic mechanism acting
grey matter, in addition to projecting to PAG, on spinal cord WDR neurons (see above), which
also sends collaterals to the locus coeruleus in transmit pain-generated information toward the
the pons (Craig 1992), which is the principal brain. Direct input of Aδ-generated information
brainstem source of noradrenergic axons. Unlike elicited by acupuncture to the subnucleus
the serotonergic axons descending from the reticularis dorsalis in the caudal medulla has
NRM, noradrenergic fibres do not operate been demonstrated in the rat and monkey
through enkephalinergic interneurons (stalked (Villanueva et al 1988, 1990); this is probably the
cells) in the spinal cord, but bring about direct same region as was shown to receive convergent
inhibition on the many types of spinal cell with nociceptive information in the cat by Bowsher
which they make synaptic contact (Fig. 6.3). (1970). The subnucleus reticularis dorsalis projects
A massive spinal projection, ascending in the downward through the dorsolateral funiculus to
anterolateral funiculus, to the gigantocellular the dorsal horn of the spinal cord at all levels
reticular region has long been known in humans (Bernard et al 1990). Bing, Villanueva & Le Bars
(Bowsher 1957). Takeshige and his colleagues (1991) have shown that this mechanism is
(1992) have also implicated the paragigantocellular brought into play by needle stimulation at both
reticular nucleus in the descending adrenergic acupoints and non-acupoints on the body surface.
system whose activity is elicited by acupuncture The fact that stimulation at non-acupoints elicits
78 THEORY AND BASIC SCIENCE

Cingulate gyrus Somatotopic projection to

sensory cortex

Prefrontal
cortex

Ventral
posterior
Diffuse cortical lateral
Fronto- projection nucleus
arcuate
connection Medial
intralaminar Thalamus
nucleus
Arcuate
N.
Descending inhibitory
pathway

OP
Hypothalamus
PAG PAG

DCS

Multisynaptic system
RF RF

nRG nRM LC
Dorsal column

NAD 5HT
?
Dorsolateral funiculus

nn
nPGC

NAd
Spinoreticular tract

Skin
R

T Tactile Αβ
E receptor DNIC
N
G

S
AB
A?

_
Spinothalamic tract

_
St SG WDR
ENK +

Painful Polymodal C +

scar nociceptor SP
VIP
Αδ

High threshhold
mechanoreceptor M
Acupuncture
 MECHANISMS OF ACUPUNCTURE 79

Figure 6.3 (facing) Adrenergic mechanism of acupuncture. Marginal cells (M), activated by Aδ pinprick receptors, in addition
to their projections to the ventral posterior lateral nucleus and the PAG (through the nucleus raphe magnus (NRM) and nucleus
raphe gigantocellularis (NRG) cells) also send axon branches to the following: (a) Subnucleus reticularis dorsalis (R) in the
caudal medulla oblongata. Descending projections from this structure bring about inhibition of noxiously generated information
arriving at the spinal cord (SG) in C nociceptors. This is the DNIC mechanism (see text).
(b) Nucleus paragigantocellularis lateralis (PGC), which indirectly (? via the locus coeruleus LC, see (c) below) brings about
noradrenergically mediated inhibition at spinal cord level. (c) The locus coeruleus at the junction of medulla oblongata and
pons. Its noradrenergic axons (NAD) are directly inhibitory to those spinal neurons with which they enter into synaptic contact.
OP = opioid peptides, DCS = dorsal column stimulation.
Note: The figure also includes the Aβ primary afferent tactile receptor, which projects to the dorsal column and in addition,
via an interneuron to the SG cells. Thus activation of the tactile receptor sends impulses to the dorsal column and also, via the
interneurone, leads to an inhibition of the SG cells, probably through the release of γ-aminobutyric acid (GABA). The latter
action will prevent information generated by noxious stimulation being transmitted further; this is believed to be the principal
mechanism of transcutaneous electrical nerve stimulation (TENS) (see Ch. 11). (After Thompson & Filshie 1993, derived from
Bowsher 1992)

DNIC does not mean that when stimulation is may also contribute in a minor way to the
performed at acupoints DNIC does not contribute acupuncture effect:
to the acupuncture effect, particularly the short- (a) The system is influenced by the pre-
term effect, as has recently been emphasized by frontal cortex and descending through the
Hashimoto & Aikawa (1993). The involvement hypothalamus (arcuate nucleus) and the PAG
of DNIC in the human acupuncture effect receives to the NRM of the medulla oblongata and
support from the recent research of Marchand & thence to the spinal cord, where enkephalinergic
Li (1993), who reported pain reduction in all skin stalked cells are activated. This system has
locations by electroacupuncture. discrete but ill-understood somatotopy, which
may depend on classical referral of stimuli, on
viscero-somatic interactions, and/or on a
CONCLUSION somatotopic organization existing within the
1. Acupuncture stimulates Aδ or Group III PAG.
small myelinated primary afferents in skin and (b) Noradrenergic cells in the lower brainstem
muscle. are excited both by influences ascending
2. Segmental acupuncture operates through a directly from the spinal cord, and also relaying
circuit involving inhibitory enkephalinergic through the nucleus paragigantocellularis, and
stalked cells in the outer part of lamina II (SG) of by influences descending from the prefrontal
the spinal grey matter, which are directly cortex through the hypothalamic arcuate
contacted by Aδ/Group III primary afferents. nucleus.
3. Heterosegmental acupuncture is brought (c) Cells of the subnucleus reticularis dorsalis
about by both a generalized neurohormonal are influenced by high-intensity inputs from
mechanism, involving the release of free β- both acupuncture and non-acupuncture points;
endorphin and apparently also of met-enkephalin, axons descending from the subnucleus
and by two descending neuronal mechanisms, reticularis dorsalis bring about widespread
the first of which is serotonergic and the second inhibition (DNIC effect).
adrenergic. A third descending system (DNIC)

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