Neuroscience provides an understanding of the organization and physiology of the nervous system. This understanding is based on an appreciation of the structure of the nervous system and on the relationship between his structure and function. The human nervous system is extraordinarilly complex.The brain is composed of about 1012 cells (neurones). These cells uniquelly possess specialized processes for receiving (dedrites) and transmitting (axons) information. These stimulus - response systems permit our body to be in contact with environmental fluctuations. There are several thousand types of nerves, neurotransmitters, receptors and chemical mediators that compose this fundamental system. Acupuncture, as needling therapy, is a kind of specialized sensory stimulation that is analysed through sensory neural pathways .
To understand, therefore, the action of Acupuncture we have to analyse the Anatomy, physiology and physiolopathology of Nervous System. In this effort we'll be helped by the knowledge of contemporary neuroendocrinology and chemoarchitecture of the brain. Many neural theories are developed to explain the mechanisms of action of Acupuncture. It is now quite clear that Acupuncture reacts in local, regional (spinal cord) and general (brain) levels. Therefore, placing one or more needles on a particular point (or area) of the body activates neural pathways on three different levels provoking local, regional, and general reactions: a)The local reaction is a multifactorial phenomenon. The electric injury potential due to the needle, the presful and synthesis of opioid peptides at the place of the injury, the substance P, histamine like substances bradikinine, serotonin, proteolitic enzymes all around the needle, occured during every needling therapy. b)The regional reaction concerns the activation of an largest area (2-3 dermotomes) through reflex arches. We can analyse the viscero-cutaneous, cutaneo-visceral, cutaneo-muscular and viscero-muscular reflexes and also the vegetative, stretch and polisynaptic segmental reflexes. c)The general reaction mainly activates the brain central mechanism of internal homeostasis. Discussing the role of central neurotransmiters we can explain the action of Acupuncture in acute and chronic pain syndromes, in addictions, in psychiatric diseases. More precisely, we shall talk about the modulatory systems that are activated through Acu points: a) opioid systems, b) non opioid systems and c) central sympathetic inhibitory mechanisms.
The application of a needle (superficially to the skin or deep into muscular or nervous tissues, ligaments or bones) is a sensory stimulation. The purpose of therapy seems to be the selective stimulation of skin points or areas of our body. Stimulation takes place at several points at the same time. It is believed that every combination of points activates different circuits and it is clear that the character of the stimulus is of primary importance for the therapeutic result.
By character of stimulation (or parameter of stimulation) we mean:
a) The depth of stimulation (skin, muscles, periosteum, ganglia)
b) The intensity of stimulation (DE CHI, electro-acupuncture, Laser)
c) The area of stimulation (acu-point, dermotome, myotome)
d) The combination of stimulation points.
In the table 1 we can see the importance of stimulation parameters and the possibilities offered by this knowledge for the systematisation of our practice.
It is well known that the nervous system with its sensory peripheral receptors, afferent sensory pathways, central cerebral nuclei, efferent pathways and effector peripheral organs directs the mechanisms of action and reaction of the body when an external or internal stimulus influences it. The various changes in the external or internal environment are handled in this manner. In the case of acupuncture, the stimulus is external (needle) and activates mostly homoeostatic mechanisms. Stimulation may be effected by simple needle (puncture - dry needling), subcutaneous infusion of pharmaceutical substances (mechanical and chemical stimulation - wet needling) or electrical stimulation (sensory block) and concerns mainly the epidermis, dermis and muscle tissue.
According to Pomeranz an injury to the skin activates the sensory receptors of small afferent nerve fibres of Aä and C axon size (Nerve fibres are classified by size and according to whether they originate in skin or muscle: large diameter myelinated nerves Ab (skin) or type I (muscle) carry «touch» and propioception, respectively. Small diameter myelinated Ad (skin) or types II and III (muscle) carry «pain». The smallest unmyelinated C (skin) and type IV (muscle) also carry «pain». Types II, III, IV and C also carry non-painful messages).
SENSORY DISTRIBUTION - MACKENZIE'S THEORY
The skin, the muscles, the ligaments, the joints, the bones, the viscera and also the vessels related to them are functionally controlled by defined segments of the spinal cord called neurotomes. Sensory afferent fibres flock towards the neurotomes coming from the dermatomes, myotomes, viscerotomes and sclerotomes according to their somotomic origin, that is to say, according to the embryonic somotomium they come from. The formation of these primitive segments or somites reflects the metamerism.
The structure of the nervous system is such that a skin area, a muscle, a group of ligaments, a viscera, the segment of a bone, are served by one and the same centre called myelotome (Mackenzie's theory, visceral-somatic convergence theory and peripheral nerve-branching theory) [2,3,4,5]. In the course of embryonic life, innervation of the bones, of the muscles of the skin and of the viscera is symmetrical. But as the organism grows it loses its initial symmetry. Finally, only the intercostal nerves preserve the initial symmetrical correspondence between neurotomes, dermatomes, myotomes and sclerotomes. The knowledge of the topographic anatomic structure of these zones, is indispensable to the acupuncturer and it possesses a particular clinical value for the localisation of diseases of the posterior or anterior roots of the spinal nerves and also for the right choice of the acupuncture points (or areas) which have to be stimulated.
Thus, according to Mackenzie's theory the sensory cutaneous stimulation (e.g. placement of a needle) will cause functional reflex reactions to the muscles, the muscle vessels and the ligaments that receive sensory or motor innervation from the same myelotome. The reflex muscle contraction, the hyperalgesia, the tenderness and the associated autonomic manifestation (sympathetic and parasympathetic hyperactivity) are localized not to the site of the injury but to an area at a distance and may involve only a small part of a dermatome. The presence of cutaneous hyperalgesia associated with deep somatic or visceral pain disorders had been recognized by many physiologists like Head, Sherrington, Ross, Sturge and others. We believe that acupuncture acts at a spinal or supraspinal level, using similar neural pathways that produse referred pain (antodromic activation of receptors at a distance). Also, according to "referred" visceral pain mechanism and to projection-convergence theory os Rusck, our skin, using his own "language" (painfull skin or muscle areas in visceral pain diseases of the heart, gallblader, stomac etc) will show to us the exactly skin area that we must stimulate to eliminate the vicious cycle of pain.
I shall mention as an example the placement of a needle (wet needling) at the acupuncture point Stomach 36 at a depth of 3 cm. This point is in the lower limbs, 1 cm outside the front margin of the leg and 3 cm below the tibial convexity (motor point of the anterior tibial muscle). This stimulation will cause:
a) Local sensory stimulation of the area of the leg that is sensorially innervated by the cutaneous branch of the major saphene nerve (neurotome L3-L4).
b) Stimulation of sensory receptors and mechano-receptors of the anterior tibial muscle (motor innervation by the deep radial nerve, L4, L5, S1 neurotome).
c) Vasoconstriction or vasodilatation (depending on the stimulation parameters) of the front tibial artery, that undertakes the cutaneous and muscular arterial irrigation of the area.
d) Myochalasis, that will influence all groups of muscles that have a common neurotomal distribution in the L5 myelotome and in particular on the long extensor of the big toe (L4, L5, S1), the long and short tibial muscle (L4, L5) and the major gluteal muscle (L5, S1, S2) and finally
e) Activation of serotoninergic and endorphinergic pain modulation systems (central action).
For all these reasons, this point is selected for stimulation in all cases of back pain or sciatica with L4-S1 pain distribution, with or without neurological findings.
Stux and Pomeranz, formulated the hypothesis that three centres are activated by acupuncture to release chemical transmitters that block pain messages.
a) The spinal cord that uses enkephalin and dynorphin (low frequency) and perhaps GABA (high frequency)
b) The midbrain uses enkephalin to activate the raphe descending system which inhibits spinal cord pain transmission by a synergic effect of the monoamines, serotonin and norepinephrine.
c) The hypothalamus-pituitary uses endorphin.
Johannes Bischko, analysing the control loop theory (feedback mechanism) states that every acupuncture point displays at least 4 criteria:
1. Local action
2. Regional action
3. An action extending beyond a certain region and
4. General action.
Watkins and Mayer [8,9] in a paper published in Science have proposed the possible activation with acupuncture (and other physical agens) of six different endogenous analgesic systems: neural opiate, hormonal opiate, neural non opiate, hormonal non opiate, unknown opiate and unknown non-opiate systems.
We could say that by placing a needle on a particular point (or area) of the body, nervous pathways are activated on three different levels provoking a) Local reactions concerning an small area of 1-3cm, b) regional (segmental) reactions concerning an area of 1-3 dermotomes and c) general reactions concerning a massive response from the Central Nervous System. We will analyse the action of acupuncture at these three levels: periphery, spinal cord and central nervous system.
LOCAL ACTION OF ACUPUNCTURE STIMULATION
This action of acupuncture is localised in a small skin area, is due in principal to the tissue lesion caused by placing the needle on the skin and concerns all acupuncture points without exception (non-specific action of acu-points).
Deactivation of superficial painful skin points.
The local reaction is the result of many factors. Initially, the difference in electric potential existing between the needle and the layers of the skin where it is placed, the difference in temperature between the needle and the skin and the quality of the needle, creates a galvanic current of low intensity. That means that the needle is a source of microenergy.[10,11]
This electric current is capable of stimulating the cell membrane, of increasing its permeability and finally of transforming the accumulation of Na and K ions in the two poles of the membrane (intra and extracellular) leading the cells, the adjacent sensory receptors and the free nervous endings to a state of excitability.
Moreover, cell injuries of the skin (an in particular of the mast cells of the Lewis layer) provoke a secretion of bradykinin, serotonin and proteolytic enzymes, ACTH and also of histamine-like substances all around the needle.
Yaksh and Hammond  point out that three types of local substances participate in peripheral transduction of nociceptive stimuli into nociceptive impulses (pain).
1) Those that activate nociceptive afferent fibres and produce pain (bradykinin, acetylcholine and potassium).
2) Those that facilitate the pain evoked by chemical and physical stimuli by sensitisation of nociceptors but are ineffective in evoking pain themselves (prostaglandins) and
3) those that produce extravasation, such as substance P. Substance P (and perhaps other peptides) may have a role in influencing the milieu of the peripheral afferent terminals, and thus in the transduction of nociceptive information. Substance P, like other peptides, is synthesised in the cell bodies of small cells (type B cells) of spinal ganglia and the gasserian ganglion by the ribosomal synthesis of large precursor prehormones.  If the stimulation of acupuncture is a kind of nociceptive stimulation, we can hypothesise the presence of this substances at the site of the needle.
Therefore, it can be said that the main neurotransmitter of pain to the periphery is substance P. Substance P is a peptide transported by the neural fibres till the last nerve terminals of the neural C-fibres. About 20% of the cell body in the spinal dorsal root ganglia contain substance P. These cells have small somas and small unmyelinated and finely myelinated axons. Their peripheral processes have been found in the epidermis and in the walls of blood vessels and glands. Their central processes project to the superficial layers of the dorsal horns of the spinal cord. Also, opioid receptors are present on primary afferent neurons (thinly myelinated and unmyelinated cutaneous nerves), on sympathetic postganglionic neurons. Now there are many findings that indicate the presence and synthesis of opioid peptides in different types of inflammatory cells at the site of tissue injury. Because the local reaction is a kind of small inflammatory reaction, the peripheral antinociceptive effect of exogenous or endogenous opioids will be enhanced especially 3-4 days after the acupuncture treatment. Substance P, together with the above mentioned substances provokes local clinical phenomena of inflammation such as swellings, red spots, itching or burning pain.
After withdrawing the needle, the unequal distribution of electrical potential (because of the high concentration of K ions) round the edges of the injury creates an electric «flux potential field» which acts as stimulator of the free nerve endings of the skin for 72 hours after the application of acupuncture. The nature of the stimulation varies according to the needle, the depth of the injury, the quality of the tissues and the readiness of the nervous system of the patient.
Inactivation of the deep painful muscle points
The quality of the stimulus depends primarily on the depth of entry of the needle and the quality of the tissue in which it is placed (target-tissue). Often, the needle is placed in muscular tissue to specific points that are painful to pressure called trigger points  or in specific muscle points called motor points (erb points).
Trigger points are painful points in muscular tissue and are detected in many degenerative disorders of the spinal cord, in all cases of musculoskeletal pain of radiculopathic origin (neuropathic pain) and in local muscle, ligament or joint injuries (especially overuse syndromes). About 70% of all acu points coincide with trigger points. Meltzack, Stillwell and Fox demostrated «a remarkably high degree (71%) of correspondence between trigger points and acupoints». Liao has also reported that many acupoints coincide with the motor points (Erb points) of skeletal muscle.
The simple placement of the needle at these points achieves: a) the inactivation of the trigger point (reduction of the intensity and discharge rate of pain sensory stimuly from the muscle to the higher sensory centres) and b) the activation of spinal reflexes. The receptor organs of the muscular shaft (propioceptive sense) and the cells of the anterior horns of the spinal cord participate in this process. This mechanism will be analysed in detail in the discussion about the regional action of acupuncture.