Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats

Repeated injection of corticosterone (CORT) induces dysregulation in the HPA axis, resulting in depression and anxiety. Many studies have shown that acupuncture, which is widely used for the treatment of stress and mental illness, in East Asian countries, is an effective therapeutic intervention for psychosomatic disorders. We investigated the influence of acupuncture therapy on chronic CORT-induced behavioral responses to the forced swimming test (FST) and elevated plus maze (EPM) and expression of neuropeptide Y (NPY) in the rat brain using immunohistochemistry. Male Sprague-Dawley rats were injected with CORT (40 mg/kg, i.p.) once daily for 19 consecutive days. The dysregulation of HPA axis by external injection of CORT was confirmed by measuring the CORT concentration in plasma and the expression level of CRF in hypothalamus. Acupuncture was performed at the PC6 acupoint for 5 min before CORT injection. Acupuncture significantly reduced depression- and anxiety-like behavior and increased NPY expression in the hypothalamus. These results demonstrated that stimulation of the PC6 acupoint suppresses the symptopathology of the hypoactivated HPA axis in chronic CORT-induced rat model of depression.

Acupuncture Effect and Central Autonomic Regulation

Abstract

Acupuncture is a therapeutic technique and part of traditional Chinese medicine (TCM). Acupuncture has clinical efficacy on various autonomic nerve-related disorders, such as cardiovascular diseases, epilepsy, anxiety and nervousness, circadian rhythm disorders, polycystic ovary syndrome (PCOS) and subfertility. An increasing number of studies have demonstrated that acupuncture can control autonomic nerve system (ANS) functions including blood pressure, pupil size, skin conductance, skin temperature, muscle sympathetic nerve activities, heart rate and/or pulse rate, and heart rate variability. Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by an imbalance between the sympathetic and parasympathetic activities but also modulates adaptive neurotransmitters in related brain regions to alleviate autonomic response. This review focused on the central mechanism of acupuncture in modulating various autonomic responses, which might provide neurobiological foundations for acupuncture effects.

Conclusion

Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by imbalance between the sympathetic and parasympathetic activities but also modulates adaptive neurotransmitter in related brain regions to alleviate autonomic response. However, it is not clear whether different pathway is activated by specific acupoint, such as local points and distant points, or the autonomic regulation effect of acupoints from different meridians. Further rigorous RCTs are required for the study of this topic. It enables us to understand the importance of acupuncture therapy in the autonomic regulation. Then, acupuncture can be used in the treatment of various autonomic disorders as a novel alternative therapy.

Acknowledgments

The study was funded by the New Century Excellent Talents in University (NCET-09-0007) and the Technology New Star Program of Beijing (2009B46).

Description text goes here

Abstract

The study of the mechanism of acupuncture action was revolutionized by the use of functional magnetic resonance imaging (fMRI). Over the past decade, our fMRI studies of healthy subjects have contributed substantially to elucidating the central effect of acupuncture on the human brain. These studies have shown that acupuncture stimulation, when associated with sensations comprising deqi, evokes deactivation of a limbic-paralimbic-neocortical network, which encompasses the limbic system, as well as activation of somatosensory brain regions. These networks closely match the default mode network and the anti-correlated task-positive network described in the literature. We have also shown that the effect of acupuncture on the brain is integrated at multiple levels, down to the brainstem and cerebellum. Our studies support the hypothesis that the effect of acupuncture on the brain goes beyond the effect of attention on the default mode network or the somatosensory stimulation of acupuncture needling. The amygdala and hypothalamus, in particular, show decreased activation during acupuncture stimulation that is not commonly associated with default mode network activity. At the same time, our research shows that acupuncture stimulation needs to be done carefully, limiting stimulation when the resulting sensations are very strong or when sharp pain is elicited. When acupuncture induced sharp pain, our studies show that the deactivation was attenuated or reversed in direction. Our results suggest that acupuncture mobilizes the functionally anti-correlated networks of the brain to mediate its actions and that the effect is dependent on the psychophysical response. In this work, we also discuss multiple avenues of future research, including the role of neurotransmitters, the effect of different acupuncture techniques, and the potential clinical application of our research findings to disease states including chronic pain, major depression, schizophrenia, autism, and Alzheimer's disease.

Conclusion

We have explored the effect of acupuncture on the brain in healthy subjects through several studies. Together these studies show that the sensations constituting deqi are associated with decreased brain activity in the limbic system and in the default mode network, while sharp pain is generally associated with signal increases in these same regions. To better group the set of regions involved in the response to acupuncture, we have defined the limbic-paralimbic-neocortical network, consisting of the amygdala, hypothalamus, and default mode network, thereby encompassing the limbic system. At the same time, we have shown that tactile sensory stimulation as control primarily affects somatosensory areas. Given our findings, we propose that the observed effect on the limbic system by acupuncture is central to its mechanism of action, and goes beyond the effect of attention on the default mode network, as described in the literature.

There are multiple avenues of future research to be pursued. To what extent neurotransmitters play a role in the response to acupuncture is little understood, and maybe elucidated through animal models or by developing avenues such as magnetic resonance spectroscopy or positron emission tomography. The extent to which differences in techniques affect the central effects and its clinical relevance needs further exploration. Finally, the clinical use of acupuncture needs further testing through well-designed clinical trials. We believe our findings of the central effect of acupuncture on the limbic system supports the testing of acupuncture for therapeutic use in affective and cognitive disease states, as well as its traditional role in the treatment of chronic pain.

Acknowledgments

The work was supported in part by the NIH/National Center for Complementary and Alternative Medicine (R21-AT00978) (1-P01-AT002048-01) (2-P01-AT002048-06) (K01-AT-002166-01), (F05-AT003770), the National Center for Research Resources (P41RR14075), the Mental Illness and Neuroscience Discovery Institute and the Brain Project Grant NS 34189. We wish to thank Nikos Makris for consultations on neuroanatomy, and Randy Buckner for useful discussions on the default mode system. There are no conflicts of interest for any author.

The effects of acupuncture on stress-induced biochemical and behavioral responses

The effects of acupuncture stimulation at PC6 (Neiguan) on chronic mild stress-induced biochemical and behavioral responses

Abstract

In the present study, the effects of acupuncture on the behavioral and physiological responses induced by chronic mild stress (CMS) were evaluated. Sprague-Dawley rats were exposed to a variety of chronic unpredictable, mild stressors for 8 weeks. The effects of acupuncture on stress-induced anxiety and anhedonia were investigated using the elevated plus maze (EPM) and sucrose intake test. In addition, c-fos expression, as an early neuronal marker in the brain was also examined utilizing Fos-like immunohistochemistry (FLI). CMS rats significantly reduced the consumption of sucrose intake and latency in the open arms of the EPM, and gained body weight more slowly, compared to non-stressed normal rats. Exposure to CMS also significantly increased FLI in the paraventricular nucleus (PVN) of the hypothalamus. Acupuncture stimulation at point PC6 on the pericardium channels (3 min), but not at other point (TE5), restored stress-induced decrease in the latency in the open arms and significantly attenuated FLI in the PVN produced by CMS. Acupuncture stimulation also tended to restore stress-induced decrease in the sucrose intake. The present results demonstrated that acupuncture was effective in restoring CMS-related biochemical and behavioral impairments such as anxiety and anhedonia and that acupuncture point was more effective than non-acupuncture point. These results suggest that acupuncture has a therapeutic effect on chronic stress-related diseases such as depression and anxiety.