Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome

Abstract Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects. We used fMRI to evaluate verum and sham acupuncture stimulation at acupoint LI‐4 in Carpal Tunnel Syndrome (CTS) patients and healthy controls (HC). CTS patients were retested after 5 weeks of acupuncture therapy. Thus, we investigated both the short‐term brain response to acupuncture stimulation, as well as the influence of longer‐term acupuncture therapy effects on this short‐term response. CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC, controlling for the non‐specific effects of sham acupuncture. A similar difference was found between CTS patients at baseline and after acupuncture therapy. For baseline CTS patients responding to verum acupuncture, functional connectivity was found between the hypothalamus and amygdala – the less deactivation in the amygdala, the greater the activation in the hypothalamus, and vice versa. Furthermore, hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients (inter‐digit separation distance). This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC, through a coordinated limbic network including the hypothalamus and amygdala.

[1]  Thomas E. Nichols,et al.  Placebo Effects Mediated by Endogenous Opioid Activity on μ-Opioid Receptors , 2005, The Journal of Neuroscience.

[2]  M Ingvar,et al.  A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy , 1999, PAIN®.

[3]  J. Binder,et al.  A Parametric Manipulation of Factors Affecting Task-induced Deactivation in Functional Neuroimaging , 2003, Journal of Cognitive Neuroscience.

[4]  T. Kaptchuk The Web That Has No Weaver : Understanding Chinese Medicine , 1983 .

[5]  M. Vangel,et al.  Brain Activity Associated with Expectancy-Enhanced Placebo Analgesia as Measured by Functional Magnetic Resonance Imaging , 2006, The Journal of Neuroscience.

[6]  B. Pomeranz,et al.  Naloxone blockade of acupuncture analgesia: endorphin implicated. , 1976, Life sciences.

[7]  V. Neugebauer,et al.  Differential sensitization of amygdala neurons to afferent inputs in a model of arthritic pain. , 2003, Journal of neurophysiology.

[8]  T. Pritsch,et al.  [Carpal tunnel syndrome]. , 2004, Harefuah.

[9]  C. Chiang,et al.  [The peripheral afferent pathway in acupuncture analgesia]. , 1974, Zhonghua yi xue za zhi.

[10]  H. Breiter,et al.  Reward Circuitry Activation by Noxious Thermal Stimuli , 2001, Neuron.

[11]  Jisheng Han Acupuncture and endorphins , 2004, Neuroscience Letters.

[12]  Peter White,et al.  Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture , 2005, NeuroImage.

[13]  V. Napadow,et al.  A systematic study of acupuncture practice: acupoint usage in an outpatient setting in Beijing, China. , 2004, Complementary therapies in medicine.

[14]  Anthony K. P. Jones,et al.  Pain processing during three levels of noxious stimulation produces differential patterns of central activity , 1997, Pain.

[15]  D. Zald The human amygdala and the emotional evaluation of sensory stimuli , 2003, Brain Research Reviews.

[16]  Peter J Keir,et al.  Pathomechanics of peripheral nerve loading. Evidence in carpal tunnel syndrome. , 2005, Journal of hand therapy : official journal of the American Society of Hand Therapists.

[17]  H. Breiter,et al.  Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study , 1999, Magnetic resonance in medicine.

[18]  B. Rosen,et al.  Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects , 2000, Human brain mapping.

[19]  R. VetrugnoMD,et al.  Sympathetic skin response , 2003 .

[20]  Jing Liu,et al.  The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI , 2005, NeuroImage.

[21]  E. Haker,et al.  Effect of sensory stimulation (acupuncture) on sympathetic and parasympathetic activities in healthy subjects. , 2000, Journal of the autonomic nervous system.

[22]  B R Rosen,et al.  Central nervous pathway for acupuncture stimulation: localization of processing with functional MR imaging of the brain--preliminary experience. , 1999, Radiology.

[23]  Jouko Siivola,et al.  Sympathetic pathology evidenced by hand thermal anomalies in carpal tunnel syndrome. , 2005, Pathophysiology : the official journal of the International Society for Pathophysiology.

[24]  Pietro Cortelli,et al.  Sympathetic skin response: basic mechanisms and clinical applications. , 2003, Clinical autonomic research : official journal of the Clinical Autonomic Research Society.

[25]  G. Vasilenko,et al.  The study of the central grey matter in mechanisms of different kinds of analgesia: Effects of lesions , 1983, Pain.

[26]  A. Sato,et al.  Calcitonin gene-related peptide produces skeletal muscle vasodilation following antidromic stimulation of unmyelinated afferents in the dorsal root in rats , 2000, Neuroscience Letters.

[27]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[28]  C. Büchel,et al.  Subcortical structures involved in pain processing: evidence from single-trial fMRI , 2002, PAIN.

[29]  J M Besson,et al.  Involvement of the spino-parabrachio -amygdaloid and -hypothalamic pathways in the autonomic and affective emotional aspects of pain. , 1996, Progress in brain research.

[30]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[31]  T. Kaptchuk,et al.  Acupuncture: Theory, Efficacy, and Practice , 2002, Annals of Internal Medicine.

[32]  T. Hisamitsu,et al.  Descending pain inhibitory system involved in acupuncture analgesia , 1992, Brain Research Bulletin.

[33]  Kevin J. Tracey,et al.  The inflammatory reflex , 2002, Nature.

[34]  B. Gerdle,et al.  Effects of acupuncture on skin and muscle blood flow in healthy subjects , 2003, European Journal of Applied Physiology.

[35]  Karl Magnus Petersson,et al.  Context-dependent Deactivation of the Amygdala during Pain , 2004, Journal of Cognitive Neuroscience.

[36]  J. Firrell,et al.  The prevalence and characteristics of nerve compression symptoms in the general population. , 2001, The Journal of hand surgery.

[37]  Jen-Chuen Hsieh,et al.  Activation of the hypothalamus characterizes the acupuncture stimulation at the analgesic point in human: a positron emission tomography study , 2001, Neuroscience Letters.

[38]  Martin Ingvar,et al.  Imaging cognitive modulation of pain processing , 2002, Pain.

[39]  E. W. Kairiss,et al.  Long‐Term synaptic potentiation in the amygdala , 1990, Synapse.

[40]  C. Carlsson Acupuncture mechanisms for clinically relevant long-term effects--reconsideration and a hypothesis. , 2010, Acupuncture in medicine : journal of the British Medical Acupuncture Society.

[41]  R. Burstein Somatosensory and visceral input to the hypothalamus and limbic system. , 1996, Progress in brain research.

[42]  V. Napadow,et al.  Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture , 2007, Human brain mapping.

[43]  Hidetoshi Mori,et al.  Decreased heart rate by acupuncture stimulation in humans via facilitation of cardiac vagal activity and suppression of cardiac sympathetic nerve , 1997, Neuroscience Letters.

[44]  Vitaly Napadow,et al.  Somatosensory cortical plasticity in carpal tunnel syndrome—a cross-sectional fMRI evaluation , 2006, NeuroImage.

[45]  H. Yamashita,et al.  Factors That Influence the Applicability of Sham Needle in Acupuncture Trials: Two Randomized, Single-Blind, Crossover Trials With Acupuncture-Experienced Subjects , 2006, The Clinical journal of pain.

[46]  E. Guney,et al.  Sympathetic skin response in idiopathic and diabetic carpal tunnel syndrome , 2005, Clinical Neurology and Neurosurgery.

[47]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Jing Liu,et al.  Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI , 2005, Human brain mapping.

[49]  C Büchel,et al.  Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. , 2002, Brain : a journal of neurology.

[50]  E. Stranden,et al.  Effects of mechanical irritation on the autonomic part of the median nerve , 2005, European journal of neurology.

[51]  Johannes Sarnthein,et al.  Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients , 2006, NeuroImage.

[52]  J M Besson,et al.  Nucleus centralis of the amygdala and the globus pallidus ventralis: electrophysiological evidence for an involvement in pain processes. , 1992, Journal of neurophysiology.

[53]  S. Stone-Elander,et al.  Anticipatory coping of pain expressed in the human anterior cingulate cortex: a positron emission tomography study , 1999, Neuroscience Letters.

[54]  A. Parent,et al.  Carpenter's Human Neuroanatomy , 1996 .

[55]  A. Freeland,et al.  Biochemistry of carpal tunnel syndrome , 2005, Microsurgery.

[56]  V. Neugebauer,et al.  The Amygdala and Persistent Pain , 2004, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[57]  J. E. Holden,et al.  Stimulation of the lateral hypothalamus produces antinociception mediated by 5-HT1A, 5-HT1B and 5-HT3 receptors in the rat spinal cord dorsal horn , 2005, Neuroscience.