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Second Issue Vol. Two; 2018 – American Journal of Acupuncture and Chinese Medicine

Acupuncture Mechanisms of action parts one

— — — Peripheral components of acupuncture stimulation — their contribution to the specific clinical effects of acupuncture

By T. Lundeberg ■ I. Lund


This charpter talking about Neuro-immunological reflex; Peripheral components of acupuncture components; stimulation — neural modulation ; Axon reflex; The peripheral sensory receptors; Axon reflex — Aδ/type III fibres; Acupuncture and mechanoreceptors; Axon reflex — C/type IV fibres; Receptive fields; Autonomic reflexes; Adaptation; Vagal-adrenal medulla reflex; Sensory threshold; Inflammatory reflex; Afferent nerve fibres; Exercise gateway reflex; Electrical stimulation of afferent; Neural influence on B cell trafficking and nerves antibody secretion; Peripheral substrate of the de qi; Connective tissue; sensation; Autocrine purinergic signalling; Local hyper or hypoesthesia following; Changes in fibroblast cell shape; acupuncture; Anisotropic tissue motion; Segmental innervation — dermatomes, Skeletal muscle; myotomes and sclerotomes; Interleukins; Spinal cord/trigeminal nucleus/brain; Growth factors; Cross talk at spinal cord levels; TGF-β superfamily; Spinal reflexes — dorsal root, motor and autonomic reflexes etc.


Key word and Abbreviations

5-HT-serotonin; Ach-acetylcholine; AMP-adenosine 5’-monophosphate; AMPK-AMP-activated protein kinase; ATP-adenosine 5’-triphosphate; BDNF-brain-derived neurotrophic factor; Ca2+-calcium ion; cAMP cyclic adenosine 5’-monophosphate; CGRP-calcitonin gene related peptide; CNS-central nervous system; CT:C-tactile; CXC-family of chemochines; DMN-default mode network; DNA-deoxyribonucleic acid; DRG-dorsal root ganglion; DRR-dorsal root reflexes; eNOS-endothelial nitric oxide synthase; EPO-erythropoietin; FGF-2-fibroblast growth factor-2; FST-follistatin-like; GABA-gamma amino butyric acid; H+-hydrogen ion; HPA-hypothalamus-pituitary-adrenal; IL-interleukin; IML-intermediolateral column; K+-potassium ion; NE-norepinephrine; NGF-nerve growth factor; NO-nitric oxide; PAG-periaqueductal grey; PG-prostaglandin; TGF-β transforming growth factor beta; TNF-tumour necrosis factor.


The content of this chapter is mainly focused on describing the possible effects of acupuncture stimulation on the body’s peripheral tissue and organs, i.e. the peripheral components of acupuncture stimulation, and the consequent effects on physiological function. In general, clinical effects following acupuncture stimulation can be described as deriving from physiological and/or psychological mechanisms where the needle stimulation could represent the artificial activation of systems obtained by natural biological effects in functional situations. The sensory stimulation that is induced by acupuncture, i.e. activation of receptors and or nerve fibres in the stimulated tissue, seem to elicit similar effects in man and other mammals, suggesting that it produces fundamental physiological changes. Hypothetically, acupuncture’s physiological counterpart of such effects on certain organ functions lies in physical exercise with strong muscle contractions.

During acupuncture stimulation sharp, thin needles are inserted into specific ‘acupuncture points’ on the body whose location may be defined by surface anatomical landmarks. Histological studies have revealed that many acupuncture points have dense innervation, and are often located in direct relation to skeletal muscles, to connective tissue, as well as to cells with neuro-immune-modulatory role (Li et al., 2004; Fig. 3.1).

1. Peripheral components of acupuncture stimulation — neural modulation


Acupuncture stimulation is associated with the activation of different sensory receptors, i.e. the terminal of the spinal dorsal root ganglion (DRG) neuron or trigeminal sensory neuron, in the skin and deeper tissues. Their properties and the corresponding sensation they give rise to, that may be activated during acupuncture and moxibustion, include five major modalities (Kandel et al;2013; Olausson et al., 2002, 2010; Schmelz et al., 1997; Sengupta and Garrity, 2013):

1.1.1: five major modalities

A. Mechanoreception (discriminative touch, size, shape, texture and movement)

B. Mechanoreception/proprioception (static position and movement)

C. Thermoreception (warmth/cold)

D. Nociception (pain)

E. Itch (itch)

1.1.2: The appearance of peripheral sensory receptors are of two types:

A. Encapsulated — nerve endings ‘covered’, often by connective tissue — mediating touch, pressure, vibration and proprioception.

B. Bare nerve endings — nerve endings that end blind in peripheral tissue — mediating nociception/pain, itch,‘emotional touch’ by gentle stroking and thermal sensations.

1.2: Mechanoreceptors: cutaneous and subcutaneous

Five major types of mechanoreceptors have been identified in glabrous (hairless) skin. Two of these are of the encapsulated type and are located in the superficial layers of the skin: Meissner’s corpuscle and the Merkel disc receptor. The other two receptors, the Pacinian corpuscle and the Ruffini ending, also encapsulated, are found in the subcutaneous and deeper tissue layers (including between layers of muscle and on interosseous membranes). Similar types of mechanoreceptor are found in the hairy skin that covers most of the body surface including the hair follicles that respond to hair displacement. The fifth major type of mechanoreceptor is the bare nerve ending responding to stroking of the hairy skin.

1.3: Mechanoreceptors: tendon, joints and skeletal muscle

Four different types of mechanoreceptor are found in skeletal muscles, tendons and joint structures.

Their main task is to give rise to the sense of movement and position of one’s own limbs and body(proprioception), and sense of speed and direction of limb movement, and also to enable maintenance of an upright position (postural information) and manipulation of objects (Table 3.1).

Possibly, activation of these receptors by acupuncture combined with exercise in patients with neurodegenerative diseases may enhance the therapeutic outcome. Furthermore, many of the effects of mobilisation and or manipulation therapeutic techniques may be explained in terms of stimulation of these muscle and joint afferents.

Ergo-receptors are activated by hard pressure during muscle contraction (Kniffki et al., 1981) and also probably by acupuncture, when the sensation of de qi is evoked. It has therefore been suggested that the physiological counterpart to acupuncture is exercise (Andersson and Lundeberg, 1995). However, the ergo-receptors can also respond to metabolic stimuli of released H+, lactate or K+ ions, i.e. acting as ‘metabolic chemoreceptor’. One of the neurotransmitters found in the ergo-receptors and also in a subgroup of afferent nerve fibres, the Aδ fibres, is calcitonin gene related peptide (CGRP) that could be released after muscle activity and acupuncture stimulation (Jansen et al., 1989; Shinbara et al., 2013). CGRP is a potent vasodilator of the capillary bed and restores flexion, extension and rotation of the joints muscle blood flow during ischemic condition throughout and after exercise or static muscle load, serving as a part of a local auto regulatory mechanism. Also, CGRP may have a trophic effect on the endothelial cells acting as a growth factor, thereby contributing to angiogenesis.

1.4: Mechanoreceptors: visceral organs

Conscious sensations are not generally experienced from the visceral organs despite the fact that they are innervated by DRG neurons with free nerve endings, similar to mechanical nociceptors in the skin. The visceral mechanoreceptors are, however, sensitive to distension and stretching of visceral muscle, which may evoke sensations of pain. Chemosensitive nerve endings on the other hand play an important role in monitoring the visceral function and provide the afferent limb for many autonomic reflexes, both sympathetic and parasympathetic. The skin of the frontal part of the body overlying the visceral organs may be more densely innervated than that of the back of the body. This could be one reason why needling the front rather than the back may evoke stronger somato-visceral reflex responses.

1.5: Thermoreceptors

Four types of thermal sensations have been detected: cold, coolness, warmth and heat. The sensations are transmitted by thermal receptors whose firing is modulated as a function of temperature. A skin temperature of 34°C, a temperature neutral zone, is perceived as neither warm nor cold. Interestingly, cool receptors fire at skin temperatures of 18–25°C, whereas warmth receptors are most active at 45°C but stop firing at 50°C. Above or below these temperatures the sensation of heat or cold pain is perceived and transmitted by activity in the hot or cold receptors. It is likely that warm and/or hot receptors are activated during moxibustion, shock wave, high-energy laser and other modalities of therapeutic warmth/heat stimulation.

1.6: Nociceptors

Nociceptors are the receptors that selectively respond to nociceptive stimulation of peripheral tissue, as mentioned earlier, leading to perceived pain under certain circumstances. Pain is sometimes perceived in the absence of this activity but could then be due to sensitization processes in higher brain structures. Several classes of nociceptor have been distinguished and may be defined on the basis of their responses to different types of stimulus (Table 3.2).

The polymodal nociceptors are the most common class of nociceptor. During intense acupuncture stimulation, acupressure (painful) or strong massage, mechanical nociceptors may be activated resulting in slight increase of pain sensations but also in an increased activity in endogenous pain inhibiting systems.

1.7: Itch

It has been postulated that pruritus receptors (Schmelz et al., 1997; Liu et al., 2009) are part of a larger set of nociceptors where activation of the whole group elicits pain while activation of the itch-selective subset elicits exclusively itch. However, itch or pruritus is not just triggered in the peripheral tissue but also more centrally suggesting that there exist multiple neural pathways for itch induction (Misery et al., 2014).


Acupuncture may activate all types of mechanoreceptor in superficial-cutaneous and in deep muscular tissue (Figs. 3.1 and 3.2). It has been reported that most acupuncture points contain abundant free nerve endings, encapsulated cutaneous receptors (Merkel, Meissner, Ruffini and Pacinian corpuscles), sarcous sensory receptors (muscle spindles and tendon organs) as well as ergo-receptors, and their afferent fibres. Acupuncture sites can be classified into three types: muscle-spindle-rich acupuncture sites, cutaneous-receptor-rich acupuncture sites and tendon-organ-rich acupuncture sites. In acupuncture practice manipulation is often performed on the inserted needles to enhance needling sensation and therapeutic responses. Different modes of stimulation technique used (e.g. superficial versus deep needling depth, light or no stimulation versus rotation and thrusting) will probably determine which type of receptor is activated. Gentle and repetitive manipulation of the inserted needle would be expected to produce mechanical pressure and tissue distortion that activate mechanoreceptors. Also, manual stimulation may result in distant effects which has been attributed to shear force- and stress-induced tissue displacements. All types of manual technique tested have yielded greater distant effects on sarcous stretch receptors than cutaneous mechanoreceptors; twist/rotation has the greatest distant effects on the cutaneous superficial and deep receptors as well as sarcous stretch receptors compared to other techniques.

In addition, the sensitivity status of the peripheral terminals, i.e. intact or sensitised as in a pain condition, will be influenced by the receptor’s peripheral milieu such as the presence of lactate, K+, nitric oxide (NO) ions, chemokines, cytokines, myokines and a number of other factors. Therefore, the same stimulation technique may produce very different sensations ranging from being barely detectable to being painful.


The peripheral region from which a sensory receptor and thereby the neuron is excited is called its receptive field. The size and structure of receptive fields differ for receptors in the superficial and deep tissue layers. A single DRG neuron innervating superficial tissue layers receives input from a cluster of Merkel disc receptors or Meissner’s corpuscles. In contrast, each nerve fibre innervating deeper layers of skin receives input from a single Ruffini ending or Pacinian corpuscle, i.e. these receptors cover large areas of skin with indistinct borders. Commonly, these receptive fields have a single ‘punctum maximum’ where the sensitivity to touch is greatest and which is located directly overlying the receptor.


Mechanoreceptors differ in adaptation properties and are overall classified into being slowly and rapidly adapting. The slowly adapting receptors like the Merkel disc receptors and the Ruffini endings signal the pressure and shape of objects by their average firing rates (the duration of the stimulus); Rapidly adapting receptors like the Meissner’s corpuscle and the Pacinian corpuscle register motion of objects,These receptors respond during the period when the position of a stimulus changes and stop firing when it comes to rest, These rapidly adapting receptors also register vertical impact (vibration) and lateral motion (stroking, rubbing or palpation).


Mechanoreceptors also differ in sensory threshold, i.e. the minimum intensity of stimulation required to generate an action potential. Rapidly adapting receptors have lower thresholds than slowly adapting receptors. The Pacinian receptors are the most sensitive mechanoreceptor and sense the frictional displacement of the skin. Whereas the Meissner’s corpuscles detect and localise small bumps since they are sensitive to abrupt changes in the shape of objects, more prominent bumps and/or edges are required to activate the slowly adapting Merkel disc receptor. The strongest response occurs when a punctate probe, like an acupuncture needle, or a sharp edge contacts the receptive field. This could explain why a punctate probe feels relatively sharp as opposed to a blunt sensation of a cotton bud.


All somatosensory information from the limbs and trunk is transmitted through individual peripheral afferent nerve fibres of spinal DRG neurons, each of which responds to the modality specific type of stimulation associated with the morphological and molecular specialisation of its peripheral receptors (Kandel et al., 2013). Somatosensory information from cranial structures is transmitted by the trigeminal sensory neurons in the brain stem, which are functionally and morphologically homologous to spinal DRG neurons, and transmitted further to higher levels in the brain via second order neurons. The principal functions of dorsal ganglion neurons and the trigeminal nerve are transduction of the stimulus and transmission of encoded stimulus information to the higher levels of the central nervous system (CNS). Starting at the DRG level there is an interaction, a ‘cross talk’, between different stimulation modalities (Table 3.3).

Recent studies also indicate that somatosensory stimulation may be transmitted to the nucleus tractus solitarius without bypassing the DRG.

Mechanoreceptors and proprioceptors are commonly innervated by large-diameter myelinated afferents axons, whereas thermal receptors and nociceptors have small myelinated or unmyelinated axons. Large fibres, Aα/I fibres, conduct action potentials at 70–120 m s−1, medium sized Aβ/II at 35–70 m s−1 and small myelinated Aδ/III at 5–35 m s−1. The unmyelinated afferent nerve fibres conduct action potentials at 0.2–2.0 m s−1. This difference in conduction velocity may be attributed to internal resistance to current flow along the axon including the saltatory conduction activity due to the spacing of the nodes of Ranvier. Gentle, dynamic touch is encoded by a distinct tactile type receptor, C Tactile (CT) afferents, and transmitted in unmyelinated afferent nerves found exclusively in hairy skin. CT afferents increase firing when the skin is stroked at a speed of ~30 mm s−1 with gentle contact at a typical skin temperature (Olausson et al., 2002; Löken etal.,2009; Morrison et al., 2010; Ackerley et al., 2014).

The presence of somatic afferent and efferent fibres innervating skin, connective tissues, and skeletal muscles has been reported at acupuncture points. Many of the acupuncture sites investigated had relatively dense neural components, particularly nerves fibres, with a ratio of nearly 1.4:1 compared to nonacupuncture points. Also, the ratio of myelinated to unmyelinated fibres was found to be nearly fourfold higher in the acupuncture point Zu-San-Li (ST36) than surrounding areas. Sarcous sensory receptors (muscle spindles and tendon organs) and their afferent fibres have been reported to be concentrated at acupuncture points located on thick muscles such as the tibialis anterior and rectus femoris muscles (Li et al., 2004).

Another important neural component of most acupuncture sites, and indeed many somatic areas, is the dense and fine autonomic nerve fibres, found in close proximity to the sensory receptors and afferents. Most autonomic nerves are norepinephrine (NE) containing sympathetic fibres but also cholinergic acetylcholine (ACh) parasympathetic efferent nerves may be found. Interaction between somatic and autonomic neural components may serve to modulate local and afferent signals in points where acupuncture stimulation is applied.

Interaction between activity in the sensory afferents and autonomic efferent nerve fibres may also take place in the DRGs and at segmental level in the spinal cord as well as in more central parts of the CNS (see Figure 3.2).


As stated earlier, the difference in the conduction velocities of different nerves may be attributed to internal resistance to current flow along the axon. This is also the reason why electrical nerve stimulation using either surface electrodes as in transcutaneous electrical nerve stimulation (TENS), or with thin needles connected to an electrical stimulator as in electro-acupuncture (EA), with low intensity, activates afferent nerves with large diameter more easily than the thinner ones (Barlas and Lundeberg, 2006). When using higher stimulation intensities, thinner sensory afferents are activated by the stimulus (Figure 3.3).

Due to the fact that EA results in the electrical activation of many different afferent nerves, it is therefore not to be regarded as equivalent to manual acupuncture (Napadow et al., 2005). It is generally accepted that manual acupuncture sets up activity in superficial and deep Aβ and Aδ fibres but that most of the clinical effects including pain alleviation and autonomic modulation may be attributed to the activation of deep Aβ, Aδ and C fibres (Andersson and Lundeberg, 1995).

8. Peripheral substrate of the de qi sensation

A large body of empirical and experimental evidence suggest that during acupuncture stimulation the so called needling sensation, de qi, should be strived for (Figure 3.4).

Although the perception of needling sensation may vary between individuals and with manual techniques, this distinct sensation is generally characterised by soreness, numbness, heaviness, distension and aching in the deep tissues surrounding the inserted needle (Hui et al., 2010). The de qi sensation is also often accompanied by an increased blood flow and a feeling of warmth at the acupuncture point. Simultaneously with the patients’ sensation of de qi, the acupuncturist often perceives an increased resistance to further movement/manipulation of the inserted needle. Thus, the needling sensation is not a single, but a compound sensation that is generated from the activation of various sensory receptors and their afferent fibres in acupuncture sites. It has been demonstrated that numbness, heaviness and distension during needling are closely associated with the activation of myelinated Aβ and Aδ afferents in deep tissues of acupuncture points, whereas aching and soreness are associated with stimulation of small myelinated Aδ and unmyelinated C fibres.


The insertion of acupuncture needles into various tissues has been reported to result in the release of mediators that can be classified as inhibitory or stimulatory. The stimulatory mediators include various cytokines, prostaglandins (PGs), bradykinin and other pro-inflammatory factors that enhance afferent fibre excitability at the acupuncture site. The inhibitory mediators include ACh, NE, gamma amino butyric acid (GABA), β-endorphin, SP, somatostatin, NO, adenosine 5′-triphosphate (ATP), cyclic guanosine monophosphate and adenosine, which suppress receptor and/or afferent fibre excitability at the acupuncture site. The predominant effect of acupuncture is to enhance the release of inhibitory mediators. Serotonin (5-HT) and histamine are also released but the effect is more complex as they can exert either inhibitory or stimulatory effects, depending upon which receptors they act on. The increase of mediators in local, peripheral tissues is partly originating from non-neuronal cells. Local mechanisms at acupuncture sites may play an important role in acupuncture-induced analgesia, in which afferent noxious signals from sites distal to needling points are blocked mostly by enhancing the activity of inhibitory mediators and activating negative feedback in acupuncture sites based on autoreceptors to SP and CGRP (Zhang et al., 2012).

Segmental innervation — dermatomes, myotomes and sclerotomes The area of skin that is innervated by a single spinal nerve is termed a dermatome and the corresponding innervation areas for muscle and skeletal tissue are termed myotome and sclerotome (see Appendix 1). In fact, the boundaries of the dermatomes, myotomes and sclerotomes are less distinct than commonly shown on distribution maps because the axons making up a spinal nerve originate from different peripheral nerves. Similarly, separate peripheral nerves contribute axons to several adjacent spinal nerves, leading to overlap in the area innervated by each segment in the spinal cord.

10. Spinal cord/trigeminal nucleus/brain

Central axons of DRG neurons branch at their entry into the spinal and trigeminal nucleus and project to nuclei in the spinal cord grey matter and brainstem. The spinal grey matter is divided into three functionally distinct regions: the dorsal horn (laminae I–VI), the intermediate zone(laminae VII) and the ventral horn (laminae VIII–IX). Lamina X consists of grey matter surrounding the central canal. The sensory specialisation of DRG neurons is maintained in the CNS through distinct ascending pathways. The modalities such as nociception, hard pressure, cutaneous touch and temperature are relayed through synapses in the spinal cord/trigeminal nucleus to the contralateral anterolateral quadrant, where axons ascend to the brain stem and thalamus in the anterolateral system. Nerve impulses induced by touch and proprioception are transmitted directly to their nucleus in the medulla through ipsilateral dorsal columns, the dorsal column-medial lemniscal system, before being transmitted to the thalamus and higher brain centres.


The spinal cord’s dorsal horn in the CNS is a key region in which sensory information is received, integrated and relayed to higher brain structures. The patterns of termination of primary afferents within the spinal cord are related to axonal diameter, receptive field and sensory modality. Nociceptive primary afferents terminate primarily in the superficial part of the dorsal horn, specifically in laminae I and II, whereas inputs from myelinated Aβ fibres of mechanoreceptors terminate in deeper layers, i.e. laminae III/IV. Thus, touch sensitive fibres terminate deeper and nociceptive sensitive fibres terminate more superficially within the dorsal horn. Excitatory and inhibitory interneurons are found throughout laminae I, II and III/IV. Neurons in lamina V receive convergent excitatory input from both non-nociceptive Aβ fibres and nociceptive Aδ and C fibres, conveying the ‘strongest’ stimulation to the higher centres of the CNS. Furthermore, the large diameter Aβ fibres inhibit the firing frequency of neurons in lamina V by activating inhibitory interneurons in laminae I/III. On the other hand the Aδ and C fibres excite lamina V neurons but also inhibit the firing of the inhibitory interneurons in lamina II, which are activated by the Aβ fibres.

In a study using intersectional genetic manipulations to identify some critical components of mechanical pain transduction, it was reported that peripheral mechanical nociceptors and Aβ mechanoreceptors, together with spinal somatisation excitatory and dynorphin inhibitory neurons, form a microcircuit that transmits and gates mechanical pain (Duan et al., 2014).

In summary, non-nociceptive afferents close and nociceptive afferents open a ‘gate’ to the central transmission of noxious input. Approximately 30% of the neurons in the superficial dorsal horn are immune-reactive for the inhibitory transmitter GABA, and/or glycine. These inhibitory neurons are driven by the activity in low-threshold primary Aβ afferents. However, it has recently been demonstrated that nearly all of the GABA containing neurons also receive input from high-threshold Aδ and/or C fibres, a combination that is not predicted by the gate control theory of pain. On the other hand, glycine containing inhibitory neurons located near the laminae II/III border may directly inhibit an enzyme that is a member of protein kinase family and involved in diverse cellular signalling pathways, the protein kinase C γ+ neurons, to close the gate. Some lamina II neurons receive tonic descending inhibition from higher brain areas via GABA and glycine containing neurons, suggesting that superficial dorsal horn neurons are inhibited through two different modes, phasic and tonic, that could be activated through peripheral and central mechanisms. Depending on the pain condition treated, possibly the short term effects of acupuncture are mediated through the phasic activity whereas the long-term effects are related to modulation of the tonic activity. This gate mechanism described earlier is the rationale for the use of TENS for the relief of pain (Barlas and Lundeberg, 2006).

The mechanism of analgesia is topographically specific, meaning that the area of the body in which pain is regulated is linked anatomically to the segments where the nociceptive and non-nociceptive afferents terminate. This would suggest that the sensory stimulation should be applied in the same segments (dermatome, myotome or sclerotome) as the pain. Furthermore, activity in non-nociceptive afferents results in inhibition of sympathetic efferents in lamina VII of the spinal cord, whereas nociceptive activity results in an activation (e.g. during needling). However, long-term needling (20–40 min) may result in the activation of centrally based inhibition of the sympathetic tone. This inhibition is more pronounced after the end of treatment and may last for hours. An even more potent counterbalance to nociception is mediated by stimulation of the periaqueductal grey (PAG) region, the grey matter that surrounds the third ventricle and the central aqueduct. This stimulation-produced analgesia activates descending pain inhibitory systems that inhibit firing of nociceptive neurons in the dorsal horn of the spinal cord. Few neurons in the PAG matter project directly to the dorsal horn of the spinal cord. Instead, they make excitatory connections with neurons, in particular serotonergic neurons, in the nucleus of raphe magnus.

From the neurons in nucleus raphe magnus they project to the spinal cord via the dorsal part of the lateral funiculus and make inhibitory connections with neurons in laminae I, II and V of the dorsal horn. Other descending inhibitory systems that suppress the activity of the nociceptive neurons in the spinal cord originate in the noradrenergic locus coeruleus and block the output of the neurons in laminae I and V by direct and indirect inhibitory actions. They also interact with opioid-containing circuits in the dorsal horn. Opiates and opioid peptides (endorphins, enkephalins and dynorphins) regulate nociceptive transmission via different mechanisms — one of these is postsynaptic inhibition, produced by increasing K+ conductance in the second order neuron, and one is presynaptic inhibition. The opioid-induced decrease in transmitter release (glutamate and SP) from primary afferents results either indirectly from a decrease in Ca2+ entry into the sensory terminals or directly from a decrease in Ca2+ conductance.

Both experimental and clinical studies suggest that part of the analgesic effect of acupuncture is mediated through activity in these descending systems that also seem to play a role in the modulation of the autonomic activity. A role for opioids is supported by the fact that morphine produces analgesia by activating descending inhibitory systems.


It has been demonstrated that descending inhibitory systems modulate dorsal root reflexes (DRR) through presynaptic inhibition and thereby inhibition of the antidromic activity in A and C primary afferent nerve fibres that contributes to the release of SP and CGRP at their peripheral terminals, so called neurogenic inflammation. This descending control of DRR is seen following activation of neurons in PAG and is mediated by GABA and 5-HT. GABA (A) receptors play a key role in the generation of DRRs, but 5-HT receptors also contribute.

The spinal cord processes somatic and visceral reflexes as well as outputs from the CNS to effector organs involved in visceral functioning including cardiovascular regulation. Since opioid or nociceptin-like immuno-reactivity is present in the spinal sympathetic nuclei (i.e. intermediolateral column, IML) it has been suggested that acupuncture, especially low frequency (2 Hz) EA, also influences the neurotransmission between the brain stem and the IML. Interestingly, both opioids and nociceptin reduce the response to rostral ventrolateral medulla-induced sympathetic excitation, indicating that the two peptides can regulate sympathetic outflow. Furthermore, afferent stimulation can modulate sympathetic activity directly through the inhibition of excitatory interneurons. These interneurons appear to form important links in the spinal cord circuitry involved in autonomic control. Taken together this suggests that acupuncture, via modulation of somato-autonomic reflexes, may modulate for example gut motility and bladder activity, a modulation that is directly related to the physiological/pathophysiological state of the organ/system (Cortelli et al., 2013).

As shown in Figure 3.5, there is an increased sympathetic activity during acupuncture stimulation (manual or electro). After the end of stimulation the effects are dependent on the basal activity before the start of stimulation. In subjects with an increased activity before the start of stimulation there is a sympathetic inhibition that may last as long as 12 h. In patients with a normal tone there is a minor inhibition which is short-lasting. In subjects with a low activity the activity stays increased after the end of stimulation. The parasympathetic tone is also affected but with a lesser magnitude but possibly with a longer duration (up to 72 h). The total net effect is a response towards the ‘normal level’.

It has also been demonstrated that acupuncture may modulate motor reflexes at the spinal cord level as well as motor behaviour, a modulation dependent on the condition treated. For example, manual acupuncture provides sufficient neuromuscular stimuli to promote immediate changes in motor unit gross recruitment without repercussion in maximal force output in healthy subjects, whereas poststroke patients did not exhibit significant reduction on the myoelectric activity and maximal force output after manual acupuncture. A common clinical experience is that acupuncture reduces muscle tenderness. This has in part been attributed to the suppression in motor neuronal activities of the skeletal muscles by needle insertion. In a healthy human, application of vibratory stimulation on the volar side of the fingertip induces a flexion reflex. Typically, the finger flexion force occurs with the onset of vibration and increases progressively during vibration. This reflex is assumed to have two reflex arcs, that is, the spinal short loop and supraspinal long loop.

Interestingly, the activities in both these loops are suppressed by ipsilateral segmental acupuncture stimulation in the upper extremity, and suppression on the supraspinal long loop is relatively long lasting (a continuous decrease of the vibration-induced finger flexion reflex was observed after removal of a needle) compared with that on the short loop. This motor reflex inhibiting effect has been attributed to the activation of nociceptive A delta or C fibres indicating that there is convergence between nociceptive and non-nociceptive afferents of different origins onto the common interneurons in segmental reflex pathways to α-motor neurons. This would suggest that noxious somatosensory input by using acupuncture could suppress motor neurons that innervate the flexor muscles through common interneurons and that acupuncture treatment could be a useful intervention for reducing muscle spasticity at least in the upper extremity (Takakura et al., 2010). The effect of acupuncture on motor reflexes and motor control needs further evaluation. (to be continued)


Abbott, R.D., Koptiuch, C., Iatridis, J.C., Howe, A.K., Badger, G.J., Langevin, H.M., 2013. Stress and matrix-responsive cytoskeletal remodeling in fibroblasts. J. Cell. Physiol. 228, 50–57.

Ackerley, R., Backlund Wasling, H., Liljencrantz, J., Olausson, H., Johnson, R.D., Wessberg, J., 2014. Human C-tactile afferents are tuned to the temperature of a skin-stroking caress. J. Neurosci. 34, 2879–2883.

Allen, D.L., Cleary, A.S., Speaker, K.J., Lindsay, S.F., Uyenishi, J., Reed, J.M., Madden, M.C., Mehan, R.S., 2008. Myostatin, activin receptor IIb, and follistatin like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am. J. Physiol. Endocrinol. Metab. 294, E918–E927.

Allen, D.L., Hittel, D.S., McPherron, A.C., 2011. Expression and function of myostatin in obesity, diabetes, and exercise adaptation. Med. Sci. Sports Exerc. 43, 1828–1835.

Andersson, S., Lundeberg, T., 1995. Acupuncture — from empiricism to science: functional background to acupuncture effects in pain and disease. Med. Hypotheses 45, 271–281.

Argiles, J.M., Lopez-Soriano, J., Almendro, V., Busquets, S., Lopez-Soriano, F.J., 2005. Cross-talk between skeletal muscle and adipose tissue: a link with obesity? Med. Res. Rev. 25, 49–65.

Arima, Y., Harada, M., Kamimura, D., Park, J.H., Kawano, F., Yull, F.E., Kawamoto, T., Iwakura, Y., Betz, U.A., Márquez, G., Blackwell, T.S., Ohira, Y., Hirano, T., Murakami, M., 2012. Regional neural activation defines a gateway for autoreactive T cells to cross the blood–brain barrier. Cell 148, 447–457.

Barlas, P., Lundeberg, T., 2006. Transcutaneous electrical nerve stimulation and acupuncture. In: McMahon, S.B., Koltzenburg, M. (Eds.), Wall and Melzack’s Textbook of pain. fifth ed. Elsevier Churchill Livingstone, Philadelphia, PA, pp. 583–591.

Bays, H.E., 2009. “Sick fat”, metabolic disease, and atherosclerosis. Am. J. Med. 22, S26–S37.

Benatti, F.B., Pedersen, B.K., 2015. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat. Rev. Rheumatol. 11, 86–97. http://dx.doi.org/10.1038/nrrheum.193.

Bergfors, M., Barnekow-Bergkvist, M., Kalezic, N., Lyskov, E., Eriksson, J.W., 2005. Short-term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity. Acta Physiol. Scand. 183, 345–356.

Bernik, T.R., Friedman, S.G., Ochani, M., DiRaimo, R., Ulloa, L., Yang, H., Sudan, S., Czura, C.J., Ivanova, S.M., Tracey, K.J., 2002. Pharmacological stimulation of the cholinergic antiinflammatory pathway. J. Exp. Med. 195, 781–788.

Berthoud, H.R., Powley, T.L., 1996. Interaction between parasympathetic and sympathetic nerves in prevertebral ganglia: morphological evidence for vagal efferent innervation of ganglion cells in the rat. Microsc. Res. Tech. 35, 80–86.

Booth, F.W., Roberts, C.K., Laye, M.J., 2012. Lack of exercise is a major cause of chronic diseases. Compr. Physiol. 2, 1143–1211.

Borovikova, L.V., Ivanova, S., Nardi, D., Zhang, M., Yang, H., Ombrellino, M., Tracey, K.J., 2000a. Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation. Auton. Neurosci. 85, 141–147.

Borovikova, L.V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G.I., Watkins, L.R., Wang, H., Abumrad, N., Eaton, J.W., Tracey, K.J., 2000b. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462.

Boström, P., Wu, J., Jedrychowski, M.P., Korde, A., Ye, L., Lo, J.C., Rasbach, K.A., Boström, E.A., Choi, J.H., Long, J.Z., Kajimura, S., Zingaretti, M.C., Vind, B.F., Tu, H., Cinti, S., Højlund, K., Gygi, S.P., Spiegelman, B.M., 2012. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463–468.

Burnstock, G., Verkhratsky, A., 2009. Evolutionary origins of the purinergic signalling system. Acta Physiol (Oxf.) 195, 415–447.

Carbo, N., Lopez-Soriano, J., Costelli, P., Alvarez, B., Busquets, S., Baccino, F.M., Quinn, L.S., Lopez-Soriano, F.J., Argiles, J.M., 2001. Interleukin-15 mediates reciprocal regulation of adipose and muscle mass: a potential role in body weight control. Biochim. Biophys. Acta 1526, 17–24.

Caron-Debarle, M., Lagathu, C., Boccara, F., Vigouroux, C., Capeau, J., 2010. HIV associated lipodystrophy: from fat injury to premature aging. Trends Mol. Med. 16, 218–229.

Chavan, S.S., Tracey, K.J., 2014. Regulating innate immunity with dopamine and electroacupuncture. Nat. Med. 20, 239–241.

Cortelli, P., Giannini, G., Favoni, V., Cevoli, S., Pierangeli, G., 2013. Nociception and autonomic nervous system. Neurol. Sci. 34 (Suppl. 1), S41–S46.

da Rocha Lapa, F., da Silva, M.D., de Almeida Cabrini, D., Santos, A.R., 2012. Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors. Purinergic Signal 8, 693–704.

Diamant, M., Tushuizen, M.E., 2006. The metabolic syndrome and endothelial dysfunction: common high-way to type 2 diabetes and CVD. Curr. Diab. Rep. 6, 279–286.

Domouzoglou, E.M., Maratos-Flier, E., 2011. Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis. Am. J. Clin. Nutr. 93, 901S–905S.

Duan, B., Cheng, L., Bourane, S., Britz, O., Padilla, C., Garcia-Campmany, L., Krashes, M., Knowlton, W., Velasquez, T., Ren, X., Ross, S.E., Lowell, B.B., Wang, Y., Goulding, M., Ma, Q., 2014. Identification of spinal circuits transmitting and gating mechanical pain. Cell 159, 1417–1432.

Feldman, B.J., Streeper, R.S., Farese Jr., R.V., Yamamoto, K.R., 2006. Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects. Proc. Natl. Acad. Sci. U. S. A. 103, 15675–15680.

Festa, A., D’Agostino Jr., R., Tracy, R.P., Haffner, S.M., 2002. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51, 1131–1137.

Fischer, C.P., Plomgaard, P., Hansen, A.K., Pilegaard, H., Saltin, B., Pedersen, B.K., 2004. Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 287, E1189–E1194.

Fox, J.R., Gray, W., Koptiuch, C., Badger, G.J., Langevin, H.M., 2014. Anisotropic tissue motion induced by acupuncture needling along intermuscular connective tissue planes. J. Altern. Complement. Med. 20, 290–294.

Furmanczyk, P.S., Quinn, L.S., 2003. Interleukin-15 increases myosin accretion in human skeletal myogenic cultures. Cell Biol. Int. 27, 845–851.

Giovannucci, E., 2007. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am. J. Clin. Nutr. 86, s836–s842.

Gleeson, M., Bishop, N.C., Stensel, D.J., Lindley, M.R., Mastana, S.S., Nimmo, M.A., 2011. The anti-

inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat. Rev. Immunol. 11, 607–615.

Goehler, L.E., Relton, J.K., Dripps, D., Kiechle, R., Tartaglia, N., Maier, S.F., Watkins, L.R., 1997. Vagal para-ganglia bind biotinylated interleukin-1 receptor antagonist: a possible mechanism for immune-to-brain communication. Brain Res. Bull. 43, 357–364.

Goldman, N., Chen, M., Fujita, T., Xu, Q., Peng, W., Liu, W., Jensen, T.K., Pei, Y., Wang, F., Han, X., Chen, J.F., Schnermann, J., Takano, T., Bekar, L., Tieu, K., Nedergaard, M., 2010. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat. Neurosci. 13, 883–888.

Goldman, N., Chandler-Militello, D., Langevin, H., Nedergaard, M., Takano, T., 2013. Purine receptor medicated actin cytoskeleton remodeling of human fibroblasts. Cell Calcium 53, 297–301.

Grabstein, K.H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., Beers, C., Richardson, J., Schoenborn, M.A., Ahdieh, M., 1994. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264, 965–968.

Guo, T., Jou, W., Chanturiya, T., Portas, J., Gavrilova, O., McPherron, A.C., 2009. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS One 4, e4937.

Handschin, C., Spiegelman, B.M., 2008. The role of exercise and PGC1[alpha] in inflammation and chronic disease. Nature 454, 463–469.

Haugen, F., Norheim, F., Lian, H., Wensaas, A.J., Dueland, S., Berg, O., Funderud, A., Skalhegg, B.S., Raastad, T., Drevon, C.A., 2010. IL-7 is expressed and secreted by human skeletal muscle cells. Am. J. Physiol. Cell Physiol. 298, C807–C816.

Hilton, D.J., Nicola, N.A., Metcalf, D., 1988. Purification of a murine leukemia inhibitory factor from Krebs ascites cells. Anal. Biochem. 173, 359–367.

Hirose, L., Nosaka, K., Newton, M., Laveder, A., Kano, M., Peake, J., Suzuki, K., 2004. Changes in inflammatory mediators following eccentric exercise of the elbow flexors. Exerc. Immunol. Rev. 10, 75–90.

Hoene, M., Weigert, C., 2008. The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. Obes. Rev. 9, 20–29.

Hojman, P., Brolin, C., Gissel, H., Brandt, C., Zerahn, B., Pedersen, B.K., Gehlb, J., 2009. Erythropoietin over-expression protects against diet-induced obesity in mice through increased fat oxidation in muscles. PLoS One 4, e5894.

Holmes, A.G., Watt, M.J., Carey, A.L., Febbraio, M.A., 2004. Ionomycin, but not physiologic doses of epinephrine, stimulates skeletal muscle interleukin-6 mRNA expression and protein release. Metabolism 53, 1492–1495.

Huang, E.J., Reichardt, L.F., 2001. Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci. 24, 677–736.

Hui, K.K., Marina, O., Liu, J., Rosen, B.R., Kwong, K.K., 2010. Acupuncture, the limbic system, and the anticorrelated networks of the brain. Auton. Neurosci. 157, 81–90.

Inoue, K., Tsuda, M., Koizumi, S., 2004. ATP- and adenosine-mediated signaling in the central nerv-

ous system: chronic pain and microglia: involvement of the ATP receptor P2X4. J. Pharmacol. Sci. 94, 112–114.

Jansen, G., Lundeberg, T., Kjartansson, J., Samuelson, U.E., 1989. Acupuncture and sensory neuropeptides increase cutaneous blood flow in rats. Neurosci. Lett. 97, 305–309.

Jonsdottir, I.H., Schjerling, P., Ostrowski, K., Asp, S., Richter, E.A., Pedersen, B.K., 2000. Muscle contractions induce interleukin-6 mRNA production in rat skeletal muscles. J. Physiol. (London) 528, 157–163.

Kami, K., Senba, E., 1998. Localization of leukemia inhibitory factor and interleukin-6 messenger ribonucleic acids in regenerating rat skeletal muscle. Muscle Nerve 21, 819–822.

Kandel, E.R., Schwartz, J.H., Jessell, T.M., 2013. Principles of Neural Science, fifth ed. McGraw-Hill, New York, ISBN: 0–8385–7701–6.

Kaufman, M.P., Hayes, S.G., 2002. The exercise pressor reflex. Clin. Auton. Res. 12, 429–439.

Kelly, M., Gauthier, M.S., Saha, A.K., Ruderman, N.B., 2009. Activation of AMP activated protein kinase (AMPK) by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization. Diabetes 58, 1953–1960.

Kim, G.Y., Lee, J.W., Ryu, H.C., Wei, J.D., Seong, C.M., Kim, J.H., 2010. Proinflammatory cytokine IL-

1beta stimulates IL-8 synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis. J. Immunol. 184, 3946–3954.

Kniffki, K.-D., Mense, S., Schmidt, R.F., 1981. Muscle receptors with fine afferent fibers which may evoke circulatory reflexes. Circ. Res. 48 (Suppl. I), 125–131.

Langevin, H.M., Churchill, D.L., Cipolla, M.J., 2001. Mechanical signaling through connective tissue: a mechanism for the therapeutic effect of acupuncture. FASEB J. 15, 2275–2282.

Langevin, H.M., Bouffard, N.A., Badger, G.J., Iatridis, J.C., Howe, A.K., 2005. Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo. Am. J. Physiol. Cell Physiol. 288, C747–C756.

Langevin, H.M., Bouffard, N.A., Badger, G.J., Churchill, D.L., Howe, A.K., 2006a. Subcutaneous tissue

fibroblast cytoskeletal remodeling induced by acupuncture: evidence for a mechanotransduction based mechanism. J. Cell. Physiol. 207, 767–774.

Langevin, H.M., Storch, K.N., Cipolla, M.J., White, S.L., Buttolph, T.R., Taatjes, D.J., 2006b. Fibroblast spreading induced by connective tissue stretch involves intracellular redistribution of alpha- and beta-actin. Histochem. Cell Biol. 125, 487–495.

Langevin, H.M., Bouffard, N.A., Churchill, D.L., Badger, G.J., 2007. Connective tissue fibroblast response to acupuncture: dose-dependent effect of bidirectional needle rotation. J. Altern. Complement. Med. 13, 355–360.

Langevin, H.M., Bouffard, N.A., Fox, J.R., Palmer, B.M., Wu, J., Iatridis, J.C., Barnes, W.D., Badger, G.J., Howe, A.K., 2011. Fibroblast cytoskeletal remodeling contributes to connective tissue tension. J. Cell. Physiol. 226, 1166–1175.

Langevin, H.M., Fujita, T., Bouffard, N.A., Takano, T., Koptiuch, C., Badger, G.J., Nedergaard, M., 2013.

Fibroblast cytoskeletal remodeling induced by tissue stretch involves ATP signaling. J. Cell. Physiol. 228, 1922–1926.

Lee, I.S., Wallraven, C., Kong, J., Chang, D.S., Lee, H., Park, H.J., Chae, Y., 2014. When pain is not only pain: inserting needles into the body evokes distinct reward-related brain responses in the context of a treatment. Physiol. Behav. 140C, 148–155.

Li, A., Dubey, S., Varney, M.L., Dave, B.J., Singh, R.K., 2003. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J. Immunol. 170, 3369–3376.

Li, A.H., Zhang, J.M., Xie, Y.K., 2004. Human acupuncture points mapped in rats are associated with excitable muscle/skin-nerve complexes with enriched nerve endings. Brain Res. 1012, 154–159.

Lin, J., Arnold, H.B., la-Fera, M.A., Azain, M.J., Hartzell, D.L., Baile, C.A., 2002. Myostatin knockout in mice increases myogenesis and decreases adipogenesis. Biochem. Biophys. Res. Commun. 291, 701–706.

Lin, J., Handschin, C., Spiegelman, B.M., 2005. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 1, 361–370.

Liu, Q., Tang, Z., Surdenikova, L., Kim, S., Patel, K.N., Kim, A., Ru, F., Guan, Y., Weng, H.J., Geng, Y., Undem, B.J., Kollarik, M., Chen, Z.F., Anderson, D.J., Dong, X., 2009. Sensory neuron-specific GPCR

Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell 139, 1353–1365.

Löken, L.S., Wessberg, J., Morrison, I., McGlone, F., Olausson, H., 2009. Coding of pleasant touch by unmyelinated afferents in humans. Nat. Neurosci. 12, 547–548.

Lundeberg, T., 2014. Electroacupuncture Induces a Release of IL-6 in the Muscle and Circulation — Possible Physiological Implications. iSAMS, Tokyo.

Lynch, M.E., Clark, A.J., Sawynok, J., 2003. Intravenous adenosine alleviates neuropathic pain: a double blind placebo controlled crossover trial using an enriched enrolment design. Pain 103, 111–117.

Mathur, N., Pedersen, B.K., 2008. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm. 2008, 109502.

Matthews, V.B., Astrom, M.B., Chan, M.H., Bruce, C.R., Krabbe, K.S., Prelovsek, O., Akerstrom, T., Yfanti, C., Broholm, C., Mortensen, O.H., Penkowa, M., Hojman, P., Zankari, A., Watt, M.J., Bruunsgaard, H.,

Pedersen, B.K., Febbraio, M.A., 2009. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia 52, 1409–1418.

Metz, C.N., Tracey, K.J., 2005. It takes nerve to dampen inflammation. Nat. Immunol. 6, 756–757.

Mina-Osorio, P., Rosas-Ballina, M., Valdes-Ferrer, S.I., Al-Abed, Y., Tracey, K.J., Diamond, B., 2012. Neural signaling in the spleen controls B cell responses to blood-borne antigen. Mol. Med. 18, 618–627.

Misery, L., Brenaut, E., Le Garrec, R., Abasq, C., Genestet, S., Marcorelles, P., Zagnoli, F., 2014. Neuropathic pruritus. Nat. Rev. Neurol. 10, 408–416.

Morrison, I., Löken, L.S., Olausson, H., 2010. The skin as a social organ. Exp. Brain Res. 204, 305–314.

Nakav, S., Chaimovitz, C., Sufaro, Y., Lewis, E.C., Shaked, G., Czeiger, D., Zlotnik, M., Douvdevani, A., 2008. Anti-inflammatory preconditioning by agonists of adenosine A1 receptor. PLoS One 3, e2107.

Napadow, V., Makris, N., Liu, J., Kettner, N.W., Kwong, K.K., Hui, K.K., 2005. Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI. Hum. Brain Mapp. 24, 193–205.

Nieman, D.C., Henson, D.A., Smith, L.L., Utter, A.C., Vinci, D.M., Davis, J.M., Kaminsky, D.E., Shute, M., 2001. Cytokine changes after a marathon race. J. Appl. Physiol. 91, 109–114.

Nieman, D.C., Henson, D.A., McAnulty, S.R., McAnulty, L., Swick, N.S., Utter, A.C., Vinci, D.M., Opiela, S.J., Morrow, J.D., 2002. Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon. J. Appl. Physiol. 92, 1970–1977.

Nieman, D.C., Davis, J.M., Henson, D.A., Walberg-Rankin, J., Shute, M., Dumke, C.L., Utter, A.C., Vinci, D.M., Carson, J.A., Brown, A., Lee, W.J., McAnulty, S.R., McAnulty, L.S., 2003. Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run. J. Appl. Physiol. 94, 1917–1925.

Nosaka, K., Clarkson, P.M., 1996. Changes in indicators of inflammation after eccentric exercise of the elbow flexors. Med. Sci. Sports Exerc. 28, 953–961.

Olausson, H., Lamarre, Y., Backlund, H., Morin, C., Wallin, B.G., Starck, G., Ekholm, S., Strigo, I., Worsley, K., Vallbo, A.B., Bushnell, M.C., 2002. Unmyelinated tactile afferents signal touch and project to insular cortex. Nat. Neurosci. 5, 900–904.

Olausson, H., Wessberg, J., Morrison, I., McGlone, F., Vallbo, A., 2010. The neurophysiology of unmyelinated tactile afferents. Neurosci. Biobehav. Rev. 34, 185–191.

Ostrowski, K., Hermann, C., Bangash, A., Schjerling, P., Nielsen, J.N., Pedersen, B.K., 1998. A trauma-like elevation of plasma cytokines in humans in response to treadmill running. J. Physiol. 513, 889–894.

Pedersen, B.K., 2000. Special feature for the Olympics: effects of exercise on the immune system: exercise and cytokines. Immunol. Cell Biol. 78, 532–535.

Pedersen, B.K., 2011. Exercise-induced myokines and their role in chronic diseases. Brain Behav. Immun. 25, 811–816.

Pedersen, B.K., 2012. Muscular IL-6 and its role as an energy sensor. Med. Sci. Sports Exerc. 44, 392–396.

Pedersen, B.K., 2013. Muscle as a secretory organ. Compr. Physiol. 3, 1337–1362.

Pedersen, B.K., Febbraio, M.A., 2008. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev. 88, 1379–1406.

Pedersen, B.K., Febbraio, M.A., 2012. Muscle, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 3, 457–465.

Pedersen, B.K., Akerstrom, T.C., Nielsen, A.R., Fischer, C.P., 2007. Role of myokines in exercise and metabolism. J. Appl. Physiol. 103, 1090–1093.

Pedersen, B.K., Pedersen, M., Krabbe, K.S., Bruunsgaard, H., Matthews, V.B., Febbraio, M.A., 2009. Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals. Exp. Physiol. 94, 1153–1160.

Petersen, E.W., Carey, A.L., Sacchetti, M., Steinberg, G.R., Macaulay, S.L., Febbraio, M.A., Pedersen, B.K., 2005. Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro: evidence that IL-6 acts independently of lipolytic hormones. Am. J. Physiol. 288, E155–E162.

Rodgers, B.D., Garikipati, D.K., 2008. Clinical, agricultural, and evolutionary biology of myostatin: a comparative review. Endocr. Rev. 29, 513–534.

Rosas-Ballina, M., Goldstein, R.S., Gallowitsch-Puerta, M., Yang, L., Valdés-Ferrer, S.I., Patel, N.B., Chavan, S., Al-Abed, Y., Yang, H., Tracey, K.J., 2009. The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE. Mol. Med. 15, 195–202.

Rosendal, L., Sogaard, K., Kjaer, M., Sjogaard, G., Langberg, H., Kristiansen, J., 2005. Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise. J. Appl. Physiol. 98, 477–481.

Ruderman, N.B., Keller, C., Richard, A.M., Saha, A.K., Luo, Z., Xiang, X., Giralt, M., Ritov, V.B., Menshikova, E.V., Kelley, D.E., Hidalgo, J., Pedersen, B.K., Kelly, M., 2006. Interleukin-6 regulation of AMP-activated protein kinase: potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 55 (Suppl. 2), S48–S54.

Rundqvist, H., Rullman, E., Sundberg, C.J., Fischer, H., Eisleitner, K., Stahlberg, M., Sundblad, P., Jansson, E., Gustafsson, T., 2009. Activation of the erythropoietin receptor in human skeletal muscle. Eur. J. Endocrinol. 161, 427–434.

Sakuma, K., Yamaguchi, A., 2011. The recent understanding of the neurotrophin’s, role in skeletal muscle adaptation. J. Biomed. Biotechnol. 2011, 201696.

Sawynok, J., 2011. Caffeine and pain. Pain 152, 726–729.

Scheele, C., Nielsen, S., Kelly, M., Broholm, C., Nielsen, A.R., Taudorf, S., Pedersen, M., Fischer, C.P., Pedersen, B.K., 2012. Satellite cells derived from obese humans with type 2 diabetes and differentiated into myocytes in vitro exhibit abnormal response to IL-6. PLoS One 7, e39657.

Schmelz, M., Schmidt, R., Bickel, A., Handwerker, H.O., Torebjörk, H.E., 1997. Specific C-receptors for itch in human skin. J. Neurosci. 17, 8003–8008.

Sengupta, P., Garrity, P., 2013. Sensing temperature. Curr. Biol. 23, R304–R307.

Shimano, M., Ouchi, N., Nakamura, K., van, W.B., Ohashi, K., Asaumi, Y., Higuchi, A., Pimentel, D.R.,

Sam, F., Murohara, T., van den Hoff, M.J., Walsh, K., 2011. Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload. Proc. Natl. Acad. Sci. U. S. A. 108, E899–E906.

Shinbara, H., Okubo, M., Kimura, K., Mizunuma, K., Sumiya, E., 2013. Participation of calcitonin gene related peptide released via axon reflex in the local increase in muscle blood flow following manual acupuncture. Acupunct. Med. 31, 81–87.

Spangenburg, E.E., Booth, F.W., 2002. Multiple signaling pathways mediate LIF induced skeletal muscle satellite cell proliferation. Am. J. Physiol. Cell Physiol. 283, C204–C211.

Spangenburg, E.E., Booth, F.W., 2006. Leukemia inhibitory factor restores the hypertrophic response to increased loading in the LIF(−/−) mouse. Cytokine 34, 125–130.

Sun, L., Ma, K., Wang, H., Xiao, F., Gao, Y., Zhang, W., Wang, K., Gao, X., IpN, Wu.Z., 2007. JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts. J. Cell Biol. 179, 129–138.

Suzuki, K., Nakaji, S., Yamada, M., Liu, Q., Kurakake, S., Okamura, N., Kumae, T., Umeda, T., Sugawara, K., 2003. Impact of a competitive marathon race on systemic cytokine and neutrophil responses. Med. Sci. Sports Exerc. 35, 348–355.

Takakura, N., Yajima, H., Takayama, M., Kawase, A., Homma, I., 2010. Inhibitory effect of needle penetration on vibration-induced finger flexion reflex in humans. Acupunct. Med. 28, 78–82.

Takano, T., Chen, X., Luo, F., Fujita, T., Ren, Z., Goldman, N., Zhao, Y., Markman, J.D., Nedergaard, M., 2012.

Traditional acupuncture triggers a local increase in adenosine in human subjects. J. Pain 13, 1215–1223.

Tjen-A-Looi, S.C., Fu, L.W., Zhou, W., Syuu, Z., Longhurst, J.C., 2005. Role of unmyelinated fibers in electroacupuncture cardiovascular responses. Auton. Neurosci. 118, 43–50.

Tomasek, J.J., Gabbiani, G., Hinz, B., Chaponnier, C., Brown, R.A., 2002. Myofibroblasts and mechanoregulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol. 3, 349–363.

Torres-Rosas, R., Yehia, G., Peña, G., Mishra, P., Thompson-Bonilla del Rocio, M., Moreno-Eutimio, M.A., Arriaga-Pizano, L.A., Isibasi, A., Ulloa, L., 2014. Dopamine mediates vagal modulation of the immune

system by electroacupuncture. Nat. Med. 20, 291–295.

Tracey, K.J., 2002. The inflammatory reflex. Nature 420, 853–859.

Tracey, K.J., 2007. Physiology and immunology of the cholinergic antiinflammatory pathway. J. Clin. Invest. 117, 289–296.

Tracey, K.J., 2012. Immune cells exploit a neural circuit to enter the CNS. Cell 148, 392–394.

Vida, G., Peña, G., Deitch, E.A., Ulloa, L., 2011. α7-Cholinergic receptor mediates vagal induction of splenic norepinephrine. J. Immunol. 186, 4340–4346.

Walsh, K., 2009. Adipokines, myokines and cardiovascular disease. Circ. J. 73, 13–18.

Watkins, L.R., Goehler, L.E., Relton, J.K., Tartaglia, N., Silbert, L., Martin, D., Maier, S.F., 1995. Blockade of interleukin-1 induced hyperthermia by subdiaphragmatic vagotomy: evidence for vagal mediation of immune-brain communication. Neurosci. Lett. 183, 27–31.

Watkins, L.R., Maier, S.F., Ochani, M., Amella, C.A., Tanovic, M., Susarla, S., Li, J.H., Wang, H., Yang, H., Ulloa, L., 1999. Implications of immune-to-brain communication for sickness and pain. Proc. Natl. Acad. Sci. U. S. A. 96, 7710–7713.

Wenz, T., Rossi, S.G., Rotundo, R.L., Spiegelman, B.M., Moraes, C.T., 2009. Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc. Natl. Acad. Sci. U. S. A. 106, 20405–20410.

Whitmer, R.A., Gustafson, D.R., Barrett-Connor, E., Haan, M.N., Gunderson, E.P., Yaffe, K., 2008. Central obesity and increased risk of dementia more than three decades later. Neurology 71, 1057–1064.

Wu, J., Boström, P., Sparks, L.M., Ye, L., Choi, J.H., Giang, A.H., Khandekar, M., Virtanen, K.A., Nuutila, P., Schaart, G., Huang, K., Tu, H., van Marken Lichtenbelt, W.D., Hoeks, J., Enerbäck, S., Schrauwen, P., Spiegelman, B.M., 2012. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366–376.

Xue, F., Michels, K.B., 2007. Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am. J. Clin. Nutr. 86, s823–s835.

Yudkin, J.S., 2007. Inflammation, obesity, and the metabolic syndrome. Horm. Metab. Res. 39, 707–709.

Zhang, Z.J., Wang, X.M., McAlonan, G.M., 2012. Neural acupuncture unit: a new concept for interpreting effects and mechanisms of acupuncture. Evid. Based Complement. Alternat. Med. 2012, 429412.

Zhou, C., Petroll, W.M., 2010. Rho kinase regulation of fibroblast migratory mechanics in fibrillar collagen matrices. Cell. Mol. Bioeng. 3, 76–83.

Zimmermann, H., 2000. Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch. Pharmacol. 362, 299–309.

Zylka, M.J., 2010. Needling adenosine receptors for pain relief. Nat. Neurosci. 13, 783–784.

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Huang Di nei jing su wen


The Huang Di nei jing su wen


Long Bojian explains the association of the Nei jing with Huang Di with two arguments. First, the Nei jing emphasizes the yin-yang and the five agents doctrines, which, according to the Shi ji, had been introduced by Zou Yan Ql. Because Zou Yan, in turn, venerated Huang Di, the Nei jing was given his name.

Second, Long Bojian quotes a passage from the Huai nan zi anl of the second century b.c.: “The ordinary people often venerate the old and de?spise the new. Hence those who set up the Way are forced to do so under the names of Shen nong and Huang Di, and it is only then that they may enter the discourse.”

Although these arguments appear inadequate to explain why this particular Nei jing was published under the pseudonym Huang Di rather than Shen nong, Bian Que, or Bai shi, the Huai nan zi at least informs us that it may have been common knowledge by the second century b.c. that scriptures carrying the names of the ancient culture heroes in their titles had not necessarily been written by these persons themselves. Of the 79 discourses constituting the textus receptus of the Su wen, 68 are structured as dialogues between Huang Di and one of three advisers, Qi (60 dialogues), Lei Gong (7 dialogues), and Gui Yuq (1 dialogue). A similar distribution of dialogues and nondialogue discourses is found in the Ling shu. Its dialogue partners include, in addition to Qi Bo and Lei Gong, Bo Gao, Shao Shi, and Shao Yu Most of the dialogues, Tessenow concludes from his analysis of historical layers in the Su wen, were the work of compilers who construed them as a device to link originally separate texts. The questions and answers put in the mouths of Huang Di and his partners allowed them to provide introductions and transitions from one theme to another. Only in a few instances, as for example in the first part of Su wen 19, should the dialogue be considered a structural characteristic of the primary text.

The textus receptus of the Su wen resulted from different primary compilations, most of them completed during the Han era. This explains the mixture of texts structured as dialogues and nondialogue discourses. Later, secondary compilators, such as Quan Yuanqi, Yang Shangshan, and Wang Bing, brought these dialogues and nondialogue discourses together or rearranged them without attempting to superimpose one coherent structure on them.

The different dialogue partners are evidence of different primary compilations too; at least they refer to an origin of “their” texts in different traditions or schools of learning. In the Su wen, the dialogues between Huang Di and Lei Gong in particular are to be distinguished from the other dialogues and must be considered a layer of their own.2 The sixty-one discourses with Qi Bo and Gui Yuqu portray Huang Di as an eager student with little knowledge of the subjects he inquires about. Only in the seven dialogues with Lei Gong does Huang Di act as sovereign teacher. Huang Di is occasionally named as the ancient Chinese culture hero who bestowed the knowledge of medicine on the Chinese people. Such statements may be justified with the final seven Lei Gong chapters, Su wen 75 through 81. The vast majority of Su wen discourses throw a different and contradictory light on the role of Huang Di. The first lines of Su wen 1 quote the first chapter of the Shi ji of 90 b.c. The editors who superimposed the dialogue structure on the Su wen texts thereby deliberately identified Huang Di as the mythical ancestor ruler of all the tribes inhabiting central China in the dis tant past.

In former times there was Huang Di.

When he came to life, he had spirituality and magic power.

While he was [still] weak, he could speak.

While he was [still] young, he was quick of apprehension.

While he grew up, he was sincere and diligent.

When he had matured, he ascended to heaven.

This Huang Di, as the Yi jing has it, rose to power after the death of Shen nong, another of the ancient Chinese culture heroes, who was credited with the introduction of materia medica into Chinese civilization.

The Huang Di of the Yi jing, the Shi ji, and Su wen was the son of Shao Dian His family name was Gongsun, and his personal name was Xuan Yuan Because his reign rested on the forces of soil and because the color of soil is yellow, his title was Yellow Di. No equivalent is available in English to reflect the meanings associated with Di in this ancient context.

A rather appealing translation of Di in English is “Lord.” In its European context, this term combines notions of a worldly and of a heavenly ruler, but the latter component is not necessarily evoked by the appearance of a Huang Di, “Yellow Lord,” in a Chinese context. Also, in the Judeo-Christian tradi?tion, the concept of Lord is tied to a monotheistic and eternal ruler in heaven. Neither of these facets is reflected in the notion of Huang Di. “Yellow Emperor” is the translation of Huang Di most often encountered in references to the Huang Di nei jing in popular English accounts. The title Emperor, however, cannot be employed in a historical-philological context because it implies solely a this-worldly rule and fails to include the notion of the mythical ruler.

Several authors have suggested rendering Di as “thearch.” This is a suitable term to emphasize the godlike qualities attributed to Di in ancient Chinese mythology Originally a “deity invoked in the religious ceremonies of earlier times,” he “had been a spirit of the storm invoked by shamans or shamanesses in rainmaking rituals, and the return of the rain at the end of the New Year season had been imagined in the form of a cosmic battle be?tween this lord of the storm and a lord of drought.”

Surprisingly, in the context of the Huang Di nei jing in many instances a very different image is evoked of “the sage who created human forms of warfare and punishments”and who “in several histories and genealogies . . . was credited with the creation of Chinese civilization and described as the primal ancestor of the Chinese people.”Not quite resembling a creator of civilization, in the Su wen Huang Di asks to be taught the most fundamental knowledge by his underlings and is occasionally rebuked for not having done enough reading.

Huang Di asked: Alas! Distant is the Way of heaven, indeed! “As if one looked up to drifting clouds, as if one looked down into a deep abyss.” [However,] when looking into a deep abyss, it is still possible to fathom [its depth]; when looking up to the drifting clouds, no one knows their farthest extension. [You,] Sir, have repeatedly spoken about the Way of heaven which you have attentively accepted. I have heard [it] and [I have] stored it. In my heart, [though,] I feel strange about it. I do not know what it means. I should like [you,] Sir, to pour out your mind and enumerate all these issues. . . .

May [I] hear about the Way of heaven?

Qi Bo paid reverence by knocking his head on the ground twice and responded:

It is brilliant, indeed, to ask about the Way of heaven!

Huang Di asked: Heaven has eight winds. The conduits have five winds.

What does that mean? Huang Di asked: Man has four regulars and twelve verticals.

What does that mean? Huang Di asked:

I should like to hear [the following]: How do the twelve depots engage each other, and what is their hierarchy? Huang Di asked:

I have heard: In heaven one relies on six [times] six terms, . . .

on the earth one relies on nine [times] nine [geographic regions] to set up calculations. . . .

I do not know what this means.

[Huang] Di:“Greatly excessive” and “inadequate,” what does that mean?

Qi Bo:[This is [outlined] in the classic.

One wonders what kind of a Di the Su wen editors may have had in mind when they let his adviser dare to refuse to answer a question and refer Huang Di to the literature instead.

In two instances, Qi Bo compares Huang Di to a Sage Di or, in the context of the imperial age, a sagelike emperor.18 In two other instances, he points out that a question asked by Huang Di pertains to the knowledge of a Shang Di, a Di on High. When the Christian Gospel was translated into Chinese, the Chinese equivalent chosen for “the Lord” was “Shang Di.” In fact, this is the only Chinese concept that comes close to the monotheistic and eternal nature of the Lord. In Su wen 9 and 69, however, Qi Bo’s references to the Di on High make it very clear, first, that this Shang Di cannot be the one and only Lord and, second, that Huang Di does not occupy the highest echelon in the hierarchy of the various Di.

Qi Bo: This was kept secret by the Lords (Di) on High; the teachers of former times have transmitted it.

[Huang] Di: May I hear about these [issues] one by one?

Qi Bo paid reverence by knocking his head to the ground twice, and responded: A lucid question, indeed! This is the brilliant Way.

This is what the Lords (Di) on High valued, what the teachers of former times have transmitted.

[I, your] subject, though not intelligent, have heard their instructions in the past.

Huang Di too is occasionally said to “have heard”or otherwise to know about events in antiquity. This puts him at a great distance from these events: Once [Huang Di] asked the Heavenly Master: I have heard that the people of high antiquity, in [the sequence of] spring and autumn, all exceeded one hundred years. But in their movements and activities there was no weakening. As for the people of today, after one half of a hundred years, the movements and activities of all of them weaken.

Is this because the times are different? or is it that the people have lost this [ability]?

Huang Di asked: I have heard that, when [healers] in antiquity treated a disease, they simply moved the essence and changed the qi.

They were able to invoke the origin [and any disease] came to an end.

When the people of nowadays treat a disease, [they employ] toxic drugs to treat their interior, and [they employ] needles and [pointed] stones to treat their exterior. Some are healed; others are not healed. Why is this so?

[Huang] Di: When the sages in high antiquity made decoctions and wines, they produced them but did not employ them.

Why was that?

In these discourses, Huang Di is a figure of “today’s world,” not of a dis? tant past. He is concerned with the well-being of his subjects and is described as having an interest in acting as a healer himself.

I wish to attend a patient, and when [I] observe [him to find out] whether [he must] die or will survive, [I should like to] cast away all doubts.

[I] should like to know the essentials — [they should be as clear] as the light of sun and moon.

May [I] hear [of this]?

[Huang] Di: When I think about the pain of the [people], this disturbs my heart.

In my confusion, contrary to [my intentions I cause their pain] to increase in severity.

I am unable to substitute their diseases [with health].

When the people hear this, they consider [me] cruel and destructive.

What is to be done?

Nevertheless, among the dialogues with Qi Bo are some that attribute to Huang Di the aloofness one expects of a Di. One is Su wen:

Huang Di sat in the Hall of Light.

In the beginning he rectified the mainstay of heaven.

He looked down [from his elevated seat] and observed the eight farthest [regions].

Having carried out investigations, he established the five constants.

The Hall of Light, ming tang, is a place where the emperor and his officials gathered for discussions in ancient times.30 Hence once he felt he had received sufficient instruction for the time being, [Huang] Di dismissed his entourage and rose. He paid reverence twice and said:

Today you have released me from ignorance and you have dispersed [my] delusions.

I shall store [this knowledge] in a Golden Chest; I shall not dare to take it out again.

As it is only in the seven dialogues with Lei Gong that Huang Di is portrayed as a capable teacher, it is here where no doubt is left of his dignity as a supreme ruler and of his superior knowledge.

At the first arrival of the first month of spring, Huang Di sat calmly.

While he looked down upon the eight farthest [regions] and rectified the qi of the eight winds,he asked Lei Gong: The categories of yin and yang, and the Way of the conduits and vessels, that is what is ruled by the five inside.

Which depot is the most precious? Huang Di examines Lei Gong, asks him about the literature he has read, rebukes him more or less severely (“How can it be that while you are old in years you ask like a child!”), and is willing, nevertheless, to “instruct him in the essentials of the perfect Way.”

Huang Di is the most prominent of the deities of shamanic cults trans? formed by the Zhou elite “into historical exemplars for their own claims to wisdom and authority.”In the Su wen, several stages or results of this trans? formation are apparent. The different historical layers of the Su wen portray different notions of Huang Di.36 There is a reference in the Su wen placing him, as did Sima Qian in the Shi ji in the first century b.c., at the very beginning of time, but no allusions can be found to Huang Di’ s role as an ancestral father of the Chinese people who instructed them how to pro Duce silk, how to construct boats and chariots, and how to write. His merits as “the fount and origin of the entire corpus of the traditional Chinese healing arts”can be upheld, as we have seen, in view only of the Lei Gong section, not of the vast majority of treatises in which he is most often portrayed as a latecomer in history, eager to study what others have initiated. This image corresponds, of course, to that conveyed in some of the Mawangdui manuscripts, where Huang Di appears as a student of seemingly disparate fields such as politics and macrobiotics.

The Di of Huang Di, it appears, is too heterogeneous a title or position to be translated throughout the Su wen with the same English term. Rather than speak of Huang Di as Yellow Di, we prefer to transliterate the entire compound and view Huang Di as a title whose meaning has changed with its historical context.

2. NEI

Because the title Huang Di nei jing has been associated with the Su wen and the Zhen jing/Jiu yuan/Ling shu only since the beginning of the third century a.d. and because it is uncertain whether the contents of the Su wen and of the Ling shu available today permit us to imagine the contents of the Huang Di nei jing mentioned in the bibliographic section of the dynastic history of the Han, it must also remain unclear whether the nature of the Su wen and of the Ling shu reveal anything about the meaning of the term nei in the Han title Huang Di nei jing. If our assumption is correct and at least some sections of today’s Su wen can be traced to the Western Han, we neverthe? less cannot be sure that these sections originated in the Huang Di nei jing or in the Huang Di wai jing or even in one of the other two (Nei jing/Wai jing pairings listed as medical classics in the bibliographic section of the dynastic history of the Han.

As we have seen, Wang Shuhe’s equation of the Western Han Huang Di nei jing with the Su wen and the Zhen jing on the basis of an identical number of juan, eighteen, may not have been justified after all, given the change in the meaning of juan between the Han and Jin dynasties. Hence one should be cautious in using the nature of the text available in today’s Nei jing to infer a conceptual opposite that could be termed Wai jing.

As Qian Chaochen has pointed out,it was not uncommon, especially during the Qin and Han dynasties, to rely on an “inner-outer” enumeration to name two parts of a text. The best known examples are Zhuang zi nei piang and Zhuang zi wai piang, as well as juan and of Han fei zi, which constitute the nei chu shuo , in contrast to juan 11 through 14, which constitute the wai chu shuo. But in none of these cases can one be sure that this “inner-outer” enumeration is assoated with any meaning distinguishing the nature of the first part of a text from the second part. It may well be that those who edited these texts and introduced the nei-wai division placed the older and more authentic con?tents of a tradition into a first, “inner,” section while they designated those materials that may have been added later and by others than an original author as secondary and “outer.”

An ancient commentary on the Han fei zi explained the title nei chu shuo as “Collected Sayings from the Interior,” that is, the plans developed by a Lord himself. Hence one should assume that wai chu shuo refers to “collected sayings” introduced from outside the palace. In this sense, the Qing-era author Wang Xianshen associated wai chu shuo with the rewards and punishments granted to officials outside the court on the basis of their speeches and behavior as far as they came to the attention of the ruler.

Two writers of the sixteenth/seventeenth century, Wu Kun dX (1551–1620), author of the Huang Di nei jing su wen zhu, and Wang Jiuda ˝, author of the Huang Di nei jing su wen ling shu he lei “1628, considered nei a reference to the five depots and to the yin and yang categorization of the human body.41 Zhang Jiebin (ca. 1563–1640) wrote in the first chapter of his Lei jing“The Lei jing combines the [contents] of the two classics and brings together related [is?sues]. The two classics bear the titles Ling shu and Su wen. Together they are called Nei jing, ‘Inner Classic.’ ‘Inner’ refers to the Way of life. A ‘classic’ is a book recording the Way.”42 Another Ming author, Yang Xun, wrote in his Zhen jiu xiang shuo wb: “Nei means ‘deep,’ ‘mysterious.’” Fang Yizhi, author of the Tong ya, stated: “[The work of] Qi [Bo] and Huang [Di] is called Nei jing because it is on the interior of the body.”

The problem with all these interpretations is, how should one think of the corresponding contents of a Wai jing? If nei referred to the “interior of the body,” should we assume that the Wai jing focused on the “exterior or outer regions of the body”? If nei meant to express the notion of “deep and mysterious,” was the Wai jing devoted to the “superficial and obvious”? And what could have been the opposite of the “Way of life” in a medical treatise? None of these differentiations is sufficiently convincing. Until a lucky find in a Western Han tomb or elsewhere presents us with a direct view of the contents of a Huang Di wai jing, one might agree with Qian Chaochen who concluded that the juxtaposition of nei and wai bears no other significance than to name two halves of a text. Similarly, Gao Bozheng interprets nei and wai as “first part” and “second part,” and he interprets nei, wai, and pang (the latter in the entry pang pian following the Bai shi wai jing) as“first part,” “second part,” and “further part.” Hence he reads Huang Di nei jing as Huang Di jing nei in the sense of “Huang Di’s scripture, first part.”However, Tessenow points out that the fact that it is the Huang Di nei jing rather than the Huang Di wai jing or the Huai nan zi nei pian rather than the Huai nan zi wai pian that has survived the passage of time may tell us that the nei part was considered more central, more important. When the Huang Di nei jing was compiled from numerous bits and pieces of texts in the Later Han era or even later still, the title Nei jing may have been chosen, as Tessenow suggests, to express the idea that this knowledge was the core knowledge.


The character jing appears in the title of quite a few ancient Chinese texts Before the compilation of the bibliographic section of the dynastic history the Western Han, the philosopher Xun zi may be one of the earliest sources to whom this association of jing and textual tradition can be traced.In the treatise Quan xue , he wrote: “Where does learning begin? Where does it end? The art starts with reciting the jing and it ends with reading the li (the rites).”The context of this passage suggests that we interpret jing as a reference to the ancient collections of songs Shi and historical documents Shu .

A more precise association of the character jing with specific texts may be found in Zhuang zi, in the chapter Tian yun, which, according to A. C. Graham, can be traced to “primitivist” philosophers active in the late third century b.c.: “Confucius said to Laodan: When I restored the six jing, that is, the Shi (Songs), the Shu (Historical Documents), the Li (Rites), the Yue (Music), the Yi (Changes), and the Chun qiu ([Annals of] Spring and Autumn), this is because I presumed them to be old.”It was only when Sima Qian spoke of the Shi jing in his account of the Confucian teaching, Ru lin lie zhuan, in his Shi ji of 90 b.c., though, that the character jing appeared in a book title. Western translations of jing in medical titles such as Huang Di nei jing or Nan jing range from “manual” to “canon” to “classic.” The etymology of the Chinese character identifies its earliest meaning as “warp,”that is, the threads running lengthwise through and holding a woven fabric. In a metaphorical sense, this meaning has been applied to various instances of “threads running lengthwise.” Hence Sima Qian spoke of the imaginary channels penetrating the human body and enabling the passage of qi as jing; likewise, Zhang Heng (78–139) termed the major roads stretching from the south of China to the north jing — a usage that was extended later in the naming of the meridians in geography.

Obviously, the term jing was used in book titles to signify statements of fundamental importance or to point to those types of knowledge whose extraordinary significance was meant to persist through the ages if not forever. If society is comparable to a fabric combining many threads of ideas and levels of hierarchy, a certain wisdom may be considered the warp holding it all together and ensuring its everlasting functioning. In a later part of Mo zi, presumably compiled circa 300 b.c., the phrase yu jing yg, translated by Graham as “expounding the canons,” may refer to the fundamental ideas of earlier Mohist moral and political philosophy.

It is not clear, then, precisely when the metaphorical meaning of jing was transferred to texts that may have been considered seminal enough to be handed down from generation to generation. The passage quoted from Xun zi above, contemporaneous with the later Mohist writings, undoubtedly refers to specific texts as jing.

The development of this usage of jing seems to have occurred in various fields of knowledge, soon to include the core of the Confucian scriptures, the six jing cited above. In the Confucian tradition, gradually an increasing number of texts were honored in this way until a total of thirteen or four?teen jing came to be acknowledged as expressions of fundamental Confucian learning.

Medicine and pharmaceutics were among the earliest subjects to be handed down to later generations in texts named jing. We have seen these titles in the bibliographic section of the dynastic history of the Western Han, which most likely took its data from the Qi of the first century b.c.; the Nan jing, a work on medical theory, and the Shen nong ben cao jing, a work on pharmaceutics, were compiled during the first century a.d. In later centuries, the scope of subjects claimed worthy of eternal transmission grew. The dynastic history of the Sui listed a Shui jing , which is the first account of the major waterways in China, as well as a Xing jing, a text focusing on astronomy. The dynastic history of the Tang introduced a Cha jing, a fundamental text on all the knowledge associated with tea. Hence a rendering of jing as“manual”may be inadequate; texts titled jing were quite the opposite of manuals. They were not meant to serve as summaries essential for carrying out this or that activity; they were seen as of fering fundamentals that presumably would stand above the changes affecting daily life for a long time to come. Even the Shen nong ben cao jing, with its detailed data on actual drug effects, may not be an exception to this idea. The total of 365 drug monographs as well as their subsumption under the threefold categorization of the universe as heaven, man, and earth suggest a basic validity that goes well beyond a manual of daily therapies. The term canon comes close to expressing the warp metaphor. It invokes the notion of “a regulation or dogma decreed by a church council,” an “authoritative list of books accepted as Holy Scripture,” the “authentic works of a writer,” or “an accepted principle or rule.51 It is true that the character jing itself was often used to express the meaning of chang dao or gui fan(norm), for example, by Meng zi sl, in Jin xin xia, when he stated glug”wo : “When a ruler acts against the norms, this will bring about the end [of his rule]. When the norms are held in proper esteem, the population prospers. Also, one might think of the core texts of Confucian learning as outlining specific norms. However, if employed in rendering individual titles such as Shi jing, Nei jing, or Shui jing, the notions associated with canon might generate a misleading idea of the contents of these books.

A classic, though, is “a work of enduring excellence.” Wu Kun (1551–1620?), author of the Huang Di nei jing su wen zhu, wrote: “A pattern revered through myriad generations is called jing.” A book or a piece of music, to name but two examples, deserves to be named a classic once it has shown it speaks to an audience beyond its own time, that is, once it is expected that its impact and acceptance will last for a long time if not forever. This, of course, is the idea behind the character jing; hence a translation of Nei jing as “Inner Classic” appears quite justified.


It has become common practice in scholarly literature not to translate but simply to transliterate the title Su wen. This book has adopted this custom too. Nevertheless, a translation should be possible; we believe the rendering“Basic Questions” comes closest to the original meaning. This intepretation was suggested by Quan Yuanqi, who flourished in the sixth century during the era of the North-South division of China and wrote the first known commentary on the Su wen. The very meaning of Su wen has been debated ever since.

As a note preceding the main text of the Su wen by Gao Baoheng and his fellow members of the eleventh-century committee responsible for compiling an authoritative edition of the text points out, Quan Yuanqi appears to have read the title as wen su. He stated: “su, is, ben. wen is: Huang Di asked (wen) Qi Bo. He broadly outlined the origins of [human] nature and the basis (ben ) of the five agents. It is for this reason that [this text] bears the title Su wen,”that is,“Questions Asking for the Origin”or“Questions Inquiring into the Basis.”Gao Baoheng et al. commented on Quan Yuanqi’s interpretation: “Even though Quan Yuanqi has offered this explanation, the meaning [of Su wen] has not become very clear. Now, the Qian zuo du states: ‘That which has physical appearance is generated by that which has no physical appearance. Hence there are the [stages] tai yi “, tai chu ”, tai shi ”l, and tai su ” Tai yi is [the stage] when the qi has not appeared yet. Tai chu is [the stage] when the qi begins [its presence]. Tai shi is [the stage] when the physical appearance begins [its presence]. Tai su is [the stage] when the dis?position [of a being] begins [its presence]. Once the qi, the physical appearance, and the disposition [of man] are complete,’ this is where illnesses can emerge from. Hence, when Huang Di asked for this tai su, the beginning [presence of human] disposition was meant. This is where the title of the Su wen originated.”Hence one might render Gao Baoheng et al.’s interpretation of Su wen as “Disposition Questions” or “Questions Inquiring into the Disposition [of Man].”

The Qian zuo du dates to the Han period. The passage referred to by Gao Baoheng et al. can be traced to the chapter Tian rui , “Celestial Omina,” in the Lie zi Cl. The bibliographic section of the dynastic history of the Western Han lists a Lie zi in the Daoist texts category. The textus recep?tus of the Lie zi was commented on by Zhang Zhan of the Eastern Jin dynasty (317–420). Its contents are heavily influenced by the thought of Lao zi and Zhuang zi and by Buddhism. There is every reason to assume that the Lie zi commented on by Zhang Zhan differed, partially or even entirely, from the Lie zi of the Western Han. To make their point, Gao Bao heng et al. did not hesitate to cut the Qian zuo du/Lie zi quote at a decisive point. The original wording was “[At this stage] the qi, the physical appearance, and the disposition [of man] are complete and do not leave each other.

Hence [this stage] is called hun lun. Hun lun is to say: the myriad beings are all tied together and do not leave each other. Gao Baoheng et al.’s interpretation suggests that the wording of the title Su wen was based on the Lie zi equation of tai su ”with zhi in the sense of su zhi or ben zhi, that is, “natural disposition” or “original disposition.” The chapter Tian di, “Heaven and Earth,” of the Bai hu tong yi by Ban Gu in the first century a.d. has a passage similar to the one in the Lie zi: “Prior to the emergence of a beginning, this is tai chu (the grand commencement), subsequent [to the emergence of a beginning], this is tai shi (the grand beginning). When the physical appearance and the omina have been completed, this is tai su (the grand origin).”To read tai su in this context, which may be the original context of the almost identical passage in the Lie zi, as “grand disposition” and to infer from this a reading of Su wen as “Disposition Questions” makes little or no sense. Hence Gao Baoheng et al.’s interpretation is difficult to accept.

Only a little earlier than Gao Baoheng et al., during the reign of Emperor Zhenzong of the Northern Song dynasty (997–1022), Zhang Junfang et al., in revising the Daoist canon, excerpted essential contents and compiled the Yun ji qi qian DC“In this context they wrote: “The pure girl (su nk) descended from heaven to cure the ills of man. [Huang] Di questioned her and compiled the Su wen,” that is the “Pure [Girl] Questions”or “Questions Directed at the Pure Girl.”No evidence whatsoever exists to support this interpretation. Although references to the mystical figure of the Pure Girl can be traced to Sima Qian’s Shi ji of 90 b.c., their early context of sexual cultivation techniques does not suggest an association with the type of medicine presented in the Su wen.

In the Southern Song era, Zhao Gongwu went to the very origins in the etymology of the character su, that is, “undyed silk,” in consider?ing the meaning of su wen and arrived at yet another conclusion. He stated in his Jun zhai du shu hou zhi”: “When the ancients spoke of Su wen, [they referred] to questions raised by Huang Di that were written on undyed silk. That is as if one said su shu, ‘written on undyed silk.’” It should be remembered here that the bibliography Qi of a.d. 23, in a section devoted to the works of the yin-yang school, lists a text named Huang Di tai su. While there is no evidence that this Huang Di tai su is related to a book named Huang Di nei ring tai su“commented on by Yang Shangshan in the eighth century and transmitted, at least in numerous fragments, until this day, it is, however, certain that the char acter su was used in its title in the metaphorical sense alluded to above, that is, “grand origin” or “grand purity,” and it appears far-fetched to assume an author of the late Western or early Eastern Han could have thought of the original etymology of su when he adopted this character to name a text.

During the Ming dynasty, Wu Kun (1551–1620?), author of the Huang Di nei jing su wen zhu, following his interpretation of jing as “a pattern revered through myriad generations,” suggested: “General investigations are called su wen.” Similarly, Ma Shi, author of the Huang Di nei jing su wen zhu zheng fa wei“of 1586, wrote:“The Su wen is a text consisting of a general dialogue between Huang Di and his six subjects Qi Bo, Gui Yuqu, Bo Gao, Shao Shi, Shao Yu, and Lei Gong.”Zhang Jiebin , author of the Lei jing, agreed: “General questions, that is meant by Su wen.”The meaning “general,” “common,” as suggested by Wu Kun, Ma Shi, and Zhang Jiebin, may well have been implied by the phrase su wen. However, one might also argue that the character su was used in a metaphorical transfer of its original meaning “white silk” in the sense of “simple,” “unadorned,” and also “empty,” “not preoccupied.”In the early Qing period, Yao Jiheng, in his “Examination of Forged Texts of All Ages,” the Gu jin wei shu kao“, came forward with yet another solution to the Su wen riddle: “My studies [suggest the following:]a Huang Di tai su is listed in the section of yin-yang specialists in the bibliographic section of the Han dynastic history. Obviously, the character su was borrowed there. Also [in this text Huang Di] asks Qi Bo questions. Hence it is called Su wen.”Tamba Genkan, the eminent Japanese Su wen commentator of the nineteenth century, continued the argument introduced by Yao Jiheng and linked it to the earlier association of Su wen with Tai su outlined by Gao Baoheng et al.: “Gao Baoheng et al. held that [Su wen] means wen tai su”, ‘questions concerning the tai su.’That is correct. The Shi ji, Yin ben ji, stated: ‘Yi Yin followed [a request by King Wu] Tang and spoke on the affairs of Su Wang˝ and the nine rulers.’The Suo yin stated: ‘Su Wang is the tai su supreme emperor. His Way is that of sincerity and purity. Hence he is called Su Wang, king of purity.’ The Lie zi and also the possibly even older Qian zuo du state: ‘Tai su is the beginning of zhi,“constitution.”’ (Tamba comments: Guan zi fil, Shui di pian Ùag :‘Su is the zhi “constitution” of the five colors.’) The Yi wen zhi lists a Huang Di tai su in 20 pian. Liu Xiang BV (77–6 b.c.), in his Bie lu quoted in his son’s Qi , stated: ‘[The Huang Di tai su] expounds [the doctrines of] yin-yang and the five agents, considering them to be the Way of Huang Di. Hence [the text] is named Tai su.’Hence the Su wen is a question-and-answer dialogue on the Tai su; this should be proof enough of the meaning of its Second Issue Vol. Two; 2018 – American Journal of Acupuncture and Chinese Medicine – Medium. That it is named Su wen rather than Wen su, this is not different from [a title such as] Tian wen”As Qian Chaochen pointed out, no antecedent is known for the construction of a book title from such diverse elements. 69 However, if Gao Baoheng et al., Yao Jiheng, and Tamba Genkan meant to indicate that the meaning of su in Su wen is identical to that of su in Huang Di tai su, they may not have been wrong after all. The tai su in Huang Di tai su may have referred to the widely shared cosmological notion of “grand simplicity” in the sense of the basics of existence unaffected by human culture. In this view, Su wen could be interpreted as “Basic Questions,” that is, questions pertaining to the basics of human existence.

It is here that we return to Quan Yuanqi, whose reading comes close at least to the intention we consider inherent in the title Su wen. Hence our rendering of the title Huang Di nei jing su wen is “Huang Di Inner Classic, Basic Questions.”

Copyright by University of California Press

Berkeley and Los Angeles, California

University of California Press, Ltd.

London, England

. 2003 by the Regents of the University of California

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