Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies Ji-Sheng Han Trends in Neurosciences 2003, 26:17-22 Brain functions are regulated by chemical messengers that include neurotransmitters and neuropeptides. Recent studies have shown that acupuncture or electrical stimulation in specific frequencies applied to certain body sites can facilitate the release of specific neuropeptides in the CNS, eliciting profound physiological effects and even activating self-healing mechanisms. Investigation of the conditions controlling this neurobiological reaction could have theoretical and clinical implications   Neuropeptides play important roles in various aspects of brain function (e.g. opioid peptides in pain control [1] and neuropeptide Y (NPY) in appetite modulation [2], among others). This review discusses evidence that neuropeptides could be mobilized by peripheral electric stimulation to benefit human health. It has been shown that physiological and pathological conditions can induce release of neuropeptides. Two well-known examples are a severe painful stimulus inducing the release of opioid peptides to ease pain, and sucking of the nipples promoting the secretion of milk. Oxytocinergic neurons fire at a very low rate, of ~1 Hz (0.1–2.6 Hz) in basal conditions, but prolonged sucking by ten or more pups can bring the firing rate up to 16–50 Hz, followed by strong milk ejection within 10–12 seconds [3]. This finding suggests that neuropeptide release could be modulated by external stimulation. Clinically, intracranial [4] or intra-spinal [5] electrical stimulation has been used through neurosurgical procedures to provide relief for patients suffering from chronic pain, with a success rate of 50–80% after one year of treatment. This pain-relief effect could involve the release of neuropeptides [6], raising the attractive possibility that non-invasive methods might be used to modulate neuropeptide release for therapeutic intervention. The question is, would such an approach be effective and practical? Frequency-dependent neuropeptide release in vitro In isolated rat neurohypophyses, field electrical stimulation induces the release of arginine vasopressin (AVP) and oxytocin (OT) into the incubation medium. Stimulation at a frequency such as 15–30 Hz was much more effective than a lower frequency such as 2–3 Hz in triggering peptide release [7], and burst stimulation was more effective than constant-frequency stimulation [8]. Furthermore, in superfused rat spinal cord slices, the release of the neuropeptide substance P (SP) per pulse of electrical stimulation was increased by frequencies in the range of 20–50 Hz, whereas release of the small-molecule neurotransmitter 5-hydroxytryptamine (5-HT) per pulse remained constant [9]. Hokfelt proposed that peptide release requires bursting or high-frequency activities, whereas individual action potentials firing at a low frequency will not induce the release of peptides [10,11] . The facilitation of peptide release by high-frequency stimulation was considered to be due to the lengthening of the action potential duration, together with the increase in frequency, leading to an increase in Ca2+ entry and in the amount of secretion per unit of action potential [12]. This concept has been supported by more recent reports [13]. However, frequency requirement can vary for different neuropeptides. In a similar experimental setting, thyrotropin-releasing hormone (TRH) could be released by electrical stimulation at a frequency as low as 0.5 and 3 Hz [14].   Go to the Full Article > >  As a BioMedNet member you have free full-text access to this article within BioMedNet Reviews for 14 days  You will have full-text access to all articles if your institute subscribes. Recommend a subscription to your librarian  There are 15,000 more Review articles in BioMedNet Reviews  Please send us your feedback on this magazine		BioMedNet Magazine 15th - 28th January 2003 Magazine Home Email to a Friend Full Article PDF printer ready version   Further Reading* Complementary and alternative medicine in neurology: hype, hope and hazards [Review] Edzard Ernst Trends in Neurosciences 2002, 25:644-645   Chronic pain: mechanisms and treatment [Review] Timothy D. Priest and Barbara Hoggart Current Opinion in Pharmacology 2002, 2:310-315   Is acupuncture effective for the treatment of chronic pain? A systematic review [Review] Jeanette Ezzo et al. Pain 2000, 86:217-225     * Full text access to the journal articles above is available to BioMedNet Reviews institutional subscribers       Related Links in BioMedNet Reviews Journal Table of Contents Table of Contents by email Related Full Text Articles Search BioMedNet Reviews