Acupuncture first captured the interest of Western science when it demonstrated its ability to induce anesthesia and analgesia. Early studies involved the infusion of cerebrospinal fluid from a rabbit that had undergone acupuncture into a naive rabbit, and resulted in the production of a significant increase in the pain threshold of the recipient rabbit . These results indicate that substances that are released from the central nervous system mediate acupuncture-induced analgesia.
Subsequent studies found that acupuncture stimulates endogenous secretions morphine-like substances called endorphins. ,  Endorphins act on the opiate receptor sites and inhibit the transmission of pain signals. There are several lines of evidence to support this action: endorphin levels in blood and cerebrospinal fluid change in response to acupuncture, naloxone and other opiate receptor antagonists block this effect, and loss of opiate receptors in genetically altered mice results in suppression of this effect. It is now known that acupuncture stimulates the secretion of not only endorphins, but a range of neurochemicals, including monoamines, that inhibit pain perception. 
It has also been demonstrated that acupuncture stimulates the type 3 small afferent fibers within muscle tissue. These fibers are connected to the hypothalamus-pituitary axis and thus can act both locally through the spinal cord, and systemically through the release of neurochemicals. The local and distal pain suppressing effects of acupuncture is dependent upon electrical stimulation of the acupuncture needle. Different frequency and intensity of electrical stimulation determines whether the effect is local (within the region of the body innervated by a single spinal nerve tract), or distally (through the systemic secretion of neurochemicals).
The ability of acupuncture to be able to regulate more complex physiological processes (beyond just pain) has been recently studied using magnetic resonance imaging (MRI). , ,  These studies suggest that stimulation of an acupuncture point leads to activation in the specific regions of the brain that correspond to the function of acupuncture points according to available medical theory in East Asia. One example is Cho et. al. studied an acupuncture point that is commonly used to treat auditory problems.  It was found that when this particular point was stimulated the auditory cortex region of the brain was shown using MRI to be activated. These studies are exciting because they make a connection between Oriental medicine theory with modern science. They suggest that acupuncture works via the nervous system.
Both the pain and MRI studies used strong stimulation of acupuncture points usually by applying an electrical current to the needle. Electrical stimulation is only occasionally used in clinical practice, and hence the relevance of these studies to acupuncture without electrical stimulation is not clear. It is also not known whether simple needle insertion and mild manipulation (as is the more usual clinical practice in the US) would activate the nervous system at all.
Connective tissue mediated mechanisms
It is also thought that acupuncture may mediate its effect through the connective tissue of the body. ,  Langevin and colleagues have demonstrated that acupuncture needles become coupled with connective tissue underlying the dermis. This mechanical event may then be transformed into a biochemical signal and through a process called mechanotransduction. The mechanical signal is postulated to act both locally (near the site of needling) and at a distance via connective tissue planes. This research may facilitate our functional understanding of how acupuncture needles placed far from the site of pain or disease work.
Several researchers have proposed that acupuncture may work via an electromagnetically based mechanism. , , ,  Several studies have shown that acupuncture points have increased conductivity and decreased resistance compared to surrounding skin.  This implies that acupuncture points conduct electrical current better than elsewhere on the body. The electrical resistance of acupuncture points varies with disease states, sleep, urination, meals, birth and delivery, physical exercise, and changes in external environment such as temperature, time of day and season. 
There are several ways (e.g., thermocoupling and bimetallic effects) in which acupuncture needles can create an electrical difference (voltage) between the end of the needle that is outside the body and the end inside the body. This voltage would promote the conduction of a current along the needle shaft and the creation of an electromagnetic (EM) field around the needle. Furthermore the shaft of the needle remaining outside the body will receive and transmit EM signals from the environment, similar to a radio antenna.
In the emerging field of bioelectromagnetics it is understood that endogenous EM fields signal and regulate physiologic states, biologic and circadian rhythms, and immune and endocrine functions. , ,  Such EM fields have the distinguishing feature of being very low-level, low-frequency, and low-intensity, similar to those generated in the body by acupuncture. Low frequency and intensity exogenous EM fields can stimulate and regulate physiological processes such as bone mending, cell division, and wound healing.  Perhaps acupuncture works in part by restoring disrupted oscillatory signals thereby adjusting physiological functioning back to normal. This approach to understanding the mechanistic basis of acupuncture will prove to be an exciting aspect of acupuncture research in the future, and will elucidate heretofore little understood biological mechanisms.
TUFTS UNIVERSITY PROGRAM IN EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE