Neurobiology of Acupuncture: Toward CAM

Abstract

It has long been accepted that acupuncture, puncturing and scraping needles at certain points on the body, can have analgesic and anesthetic effects, as well as therapeutic effects in the treatment of various diseases. This therapy, including acupuncture anesthesia, has drawn the attention of many investigators and become a research subject of international interest around the world. Numerous studies have demonstrated that the nervous system, neurotransmitters, endogenous substances and Jingluo (meridians) may respond to needling stimulation and electrical acupuncture. An abundance of information has now accumulated concerning the neurobiological mechanisms of acupuncture, in relation to both neural pathways and neurotransmitters/hormonal factors that mediate autonomic regulation, pain relief and other therapeutics. Early studies demonstrated that the analgesic effects of electroacupuncture (EA) are mediated by opioid peptides in the periaqueductal gray. Recent evidence shows that nitric oxide plays an important role in mediating the cardiovascular responses to EA stimulation through the gracile nucleus-thalamic pathway. Other substances, including serotonin, catecholamines, inorganic chemicals and amino acids such as glutamate and alpha-aminobutyric acid (GABA), are proposed to mediate certain cardiovascular and analgesic effects of acupuncture, but at present their role is poorly understood. The increased interest in acupuncture health care has led to an ever-growing number of investigators pursuing research in the processes of the sense of needling touch, transduction of needling stimulation signals, stimulation parameters and placebos. In this Review, the evidence and understanding of the neurobiological processes of acupuncture research have been summarized with an emphasis on recent developments of nitric oxide mediating acupuncture signals through the dorsal medulla-thalamic pathways.

Figure 1

Neural circuits related to somatosympathetic reflexes in the gracile-thalamic-cortex pathways. Axonal tracing studies show that cutaneous primary afferents projecting from the hindlimb to the medulla are distributed mainly in the gracile nucleus, and synapses from the gracile nucleus, which receive somatosensory afferent inputs project to the thalamus. Acupuncture stimulation of hindlimb, similar to electrical stimulus to the tibial nerve causes NO-mediated activation of somatosympathetic reflexes in this pathway resulting in sympathoinhibition and analgesia.

Figure 2

Frequency-dependent changes in mean arterial pressure (MAP, top) and heart rate (bottom) induced by EA ST36 in anesthetized Sprague–Dawley rats. Hypotensive and bradycardiac responses to EA stimulation of ST36 were significantly blocked by microinjection of lidocaine into gracile nucleus (P < 0.05, analysis of variance, n = 7/group). Parameters of stimulation: 6 V, 1 ms pulse duration, 3, 10 and 30 Hz for 10 s. [Reproduced with permission from Chen and Ma (44).]

Figure 3

Frequency–response curves for changes in mean arterial blood pressure (MAP) in responses to EA stimulation of ST36 before and after microinjection of L-arginine into the gracile nucleus in anesthetized rats. Microinjection of L-arginine into the gracile nucleus enhanced the depressor and bradycardiac responses to EA ST36 (P < 0.05, analysis of variance, n = 5/group). Other details are shown in legend to figure 2. [Reproduced with permission from Chen and Ma (44).]

Figure 4

Time response histogram of antisense oligos to nNOS in the gracile nucleus on the cardiovascular responses caused by EA ST36 in rats. The depressor (top) and bradycardiac responses (bottom) were inhibited by microinjection of nNOS antisense oligos into the gracile nucleus (P < 0.05, analysis of variance, n = 5/group). The inhibiting effects began at 30 min after injection, and the maximum effects occurred at 45 min. The effects reversed at 90 min after the injection. Microinjection of nNOS sense oligos into the gracile nucleus did not alter the responses to stimulation of ST36. Other details are shown in legend to figure 2. [Reproduced with permission from Chen and Ma (44).]