Medullary substrate and differential cardiovascular responses during stimulation of specific acupoints

Electroacupuncture (EA) at P5–P6 acupoints overlying the median nerve reduces premotor sympathetic cardiovascular neuronal activity in the rostral ventral lateral medulla (rVLM) and visceral reflex pressor responses. In previous studies, we have noted different durations of influence of EA comparing P5–P6 and S36–S37 acupoints, suggesting that point specificity may exist. The purpose of this study was to evaluate the influence of stimulating P5–P6 (overlying the median nerve), LI4–L7 (overlying branches of the median nerve and the superficial radial nerve), LI6–LI7 (overlying the superficial radial nerve), LI10–LI11 (overlying the deep radial nerves), S36–S37 (overlying the deep peroneal nerves), or K1–B67 (overlying terminal branches of the tibial nerves) specific acupoints, overlying deep and superficial somatic nerves, on the excitatory cardiovascular reflex and rVLM responses evoked by stimulation of chemosensitive receptors in the cat's gallbladder with bradykinin (BK) or direct splanchnic nerve (SN) stimulation. We observed point-specific differences in magnitude and duration of EA inhibition between P5–P6 or LI10–LI11 and LI4–L7 or S36–S37 in responses to 30-min stimulation with low-frequency, low-current EA. EA at LI6–LI7 and K1–B67 acupoints as well as direct stimulation of the superficial radial nerve did not cause any cardiovascular or rVLM neuronal effects. Cardiovascular neurons in the rVLM, a subset of which were classified as premotor sympathetic cells, responded to brief (30 s) stimulation of the SN as well as acupoints P5–P6, LI10–LI11, LI4–L7, S36–S37, LI6–LI7, or K1–B67, or underlying somatic pathways in a fashion similar to the reflex responses. In fact, we observed a significant linear relationship ( r2 = 0.71) between the evoked rVLM response and reflex change in mean arterial blood pressure. In addition, EA stimulation at P5–P6 and LI4–L7 decreased rVLM neuronal activity by 41 and 12%, respectively, for >1 h, demonstrating that prolonged input into the medulla during stimulation of somatic nerves, depending on the degree of convergence, leads to more or less inhibition of activity of these cardiovascular neurons. Thus EA at acupoints overlying deep and superficial somatic nerves leads to point-specific effects on cardiovascular reflex responses. In a similar manner, sympathetic cardiovascular rVLM neurons that respond to both visceral (reflex) and somatic (EA) nerve stimulation manifest graded responses during stimulation of specific acupoints, suggesting that this medullary region plays a role in site-specific inhibition of cardiovascular reflex responses by acupuncture.

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Brain stem mechanisms underlying acupuncture modality-related modulation of cardiovascular responses in rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.01365.2004 ◽

2005 ◽

Vol 99 (3) ◽

pp. 851-860 ◽

Cited By ~ 54

Author(s):

Wei Zhou (Yi Syuu) ◽

Stephanie C. Tjen-A-Looi ◽

John C. Longhurst

Keyword(s):

Brain Stem ◽

Median Nerve ◽

Sympathetic Neurons ◽

Low Frequency ◽

Cardiovascular Responses ◽

Splanchnic Nerve ◽

Thoracic Spinal Cord ◽

Median Nerve Stimulation ◽

Cardiovascular Neurons ◽

Stimulation Of

The present study was designed to investigate brain stem responses to manual acupuncture (MA) and electroacupuncture (EA) at different frequencies at pericardial P (5–6) acupoints located over the median nerve. Activity of premotor sympathetic cardiovascular neurons in the rostral ventral lateral medulla (rVLM) was recorded during stimulation of visceral and somatic afferents in ventilated anesthetized rats. We stimulated either the splanchnic nerve at 2 Hz (0.1–0.4 mA, 0.5 ms) or the median nerve for 30 s at 2, 10, 20, 40, or 100 Hz using EA (0.3–0.5 mA, 0.5 ms) or at ∼2 Hz with MA. Twelve of 18 cells responsive to splanchnic and median nerve stimulation could be antidromically driven from the intermediolateral columns of the thoracic spinal cord, T2–T4, indicating that they were premotor sympathetic neurons. All 18 neurons received baroreceptor input, providing evidence of their cardiovascular sympathoexcitatory function. Evoked responses during stimulation of the splanchnic nerve were inhibited by 49 ± 6% ( n = 7) with EA and by 46 ± 4% ( n = 6) with MA, indicating that the extent of inhibitory effects of the two modalities were similar. Inhibition lasted for 20 min after termination of EA or MA. Cardiovascular premotor rVLM neurons responded to 2-Hz electrical stimulation at P 5–6 and to a lesser extent to 10-, 20-, 40-, and 100-Hz stimulation (53 ± 10, 16 ± 2, 8 ± 2, 2 ± 1, and 0 ± 0 impulses/30 stimulations, n = 7). These results indicate that rVLM premotor sympathetic cardiovascular neurons that receive convergent input from the splanchnic and median nerves during low-frequency EA and MA are inhibited similarly for prolonged periods by low-frequency MA and EA.

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Emergence of Radial Nerve Dominance in Median Nerve Cortex After Median Nerve Transection in an Adult Squirrel Monkey

Journal of Neurophysiology ◽

10.1152/jn.1997.77.1.522 ◽

1997 ◽

Vol 77 (1) ◽

pp. 522-526 ◽

Cited By ~ 26

Author(s):

C. E. Schroeder ◽

S. Seto ◽

P. E. Garraghty

Keyword(s):

Median Nerve ◽

Squirrel Monkey ◽

Ulnar Nerve ◽

Action Potentials ◽

Radial Nerve ◽

Current Source ◽

Short Latency ◽

Nerve Transection ◽

A Site ◽

Stimulation Of

Schroeder, C. E., S. Seto, and P. E. Garraghty. Emergence of radial nerve dominance in median nerve cortex after median nerve transection in an adult squirrel monkey. J. Neurophysiol. 77: 522–526, 1997. Throughout the glabrous representation in Area 3b, electrical stimulation of the dominant (median or ulnar) input produces robust, short-latency excitation, evident as a net extracellular “sink” in the Lamina 4 current source density (CSD) accompanied by action potentials. Stimulation of the collocated nondominant (radial nerve) input produces a subtle short-latency response in the Lamina 4 CSD unaccompanied by action potentials and followed by a clear excitatory response 12–15 ms later. Laminar response profiles for both inputs have a “feedforward” pattern, with initial activation in Lamina 4, followed by extragranular laminae. Such corepresentation of nondominant radial nerve inputs with the dominant (median or ulnar nerve) inputs in the glabrous hand surface representation provides a likely mechanism for reorganization after median nerve section in adult primates. To investigate this, we conducted repeated recordings using an implanted linear multi-electrode array straddling the cortical laminae at a site in “median nerve cortex” (i.e., at a site with a cutaneous receptive field on the volar surface of D2 and thus with its dominant afferent input conveyed by the median nerve) in an adult squirrel monkey. We characterized the baseline responses to median, radial, and ulnar nerve stimulation. We then cut the median nerve and semi-chronically monitored radial nerve, ulnar nerve and median nerve (proximal stump) evoked responses. The radial nerve response in median nerve cortex changed progressively during the weeks after median nerve transection, ultimately assuming the characteristics of the dominant nerve profile. During this time, median, and ulnar nerve profiles displayed little or no change.

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Direct MRI mapping of neuronal activity evoked by electrical stimulation of the median nerve at the right wrist

Magnetic Resonance in Medicine ◽

10.1002/mrm.21857 ◽

2009 ◽

Vol 61 (5) ◽

pp. 1073-1082 ◽

Cited By ~ 23

Author(s):

Yiqun Xue ◽

Xiying Chen ◽

Thomas Grabowski ◽

Jinhu Xiong

Keyword(s):

Electrical Stimulation ◽

Median Nerve ◽

Neuronal Activity ◽

The Right ◽

Stimulation Of

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Modulation of cardiovascular excitatory responses in rats by transcutaneous magnetic stimulation: role of the spinal cord

Journal of Applied Physiology ◽

10.1152/japplphysiol.01130.2005 ◽

2006 ◽

Vol 100 (3) ◽

pp. 926-932 ◽

Cited By ~ 19

Author(s):

Wei Zhou (Yi Syuu) ◽

Ian Hsiao ◽

Vernon W. H. Lin ◽

John C. Longhurst

Keyword(s):

Spinal Cord ◽

Median Nerve ◽

Opioid Receptors ◽

Magnetic Stimulation ◽

Pressor Response ◽

Intrathecal Injection ◽

Cardiovascular Responses ◽

Opioid Antagonist ◽

Gastric Distension ◽

Cardiovascular Reflex

This study investigated the efficacy of magnetic stimulation on the reflex cardiovascular responses induced by gastric distension in anesthetized rats and compared these responses to those influenced by electroacupuncture (EA). Unilateral magnetic stimulation (30% intensity, 2 Hz) at the Jianshi-Neiguan acupoints (pericardial meridian, P 5–6) overlying the median nerve on the forelimb for 24 min significantly decreased the reflex pressor response by 32%. This effect was noticeable by 20 min of magnetic stimulation and continued for 24 min. Median nerve denervation abolished the inhibitory effect of magnetic stimulation, indicating the importance of somatic afferent input. Unilateral EA (0.3–0.5 mA, 2 Hz) at P 5–6 using similar durations of stimulation similarly inhibited the response (35%). The inhibitory effects of EA occurred earlier and were marginally longer (20 min) than magnetic stimulation. Magnetic stimulation at Guangming-Xuanzhong acupoints (gallbladder meridian, GB 37–39) overlying the superficial peroneal nerve on the hindlimb did not attenuate the reflex. Intravenous naloxone immediately after termination of magnetic stimulation reversed inhibition of the cardiovascular reflex, suggesting involvement of the opioid system. Also, intrathecal injection of δ- and κ-opioid receptors antagonists, ICI174,864 ( n = 7) and nor-binaltorphimine ( n = 6) immediately after termination of magnetic stimulation reversed inhibition of the cardiovascular reflex. In contrast, the μ-opioid antagonist CTOP ( n = 7) failed to alter the cardiovascular reflex. The endogenous neurotransmitters for δ- and κ-opioid receptors, enkephalins and dynorphin but not β-endorphin, therefore appear to play significant roles in the spinal cord in mediating magnetic stimulation-induced modulation of cardiovascular reflex responses.

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Splenic and renal sympathetic responses to stimulation of splenic receptors in cats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1984.247.5.r856 ◽

1984 ◽

Vol 247 (5) ◽

pp. R856-R865 ◽

Cited By ~ 5

Author(s):

F. R. Calaresu ◽

J. C. Tobey ◽

S. R. Heidemann ◽

L. C. Weaver

Keyword(s):

Venous Pressure ◽

Electron Microscopic Examination ◽

Physiological Saline ◽

Cardiovascular Responses ◽

Systemic Arterial Pressure ◽

Renal Nerves ◽

Electron Microscopic ◽

Reflex Responses ◽

Adequate Stimulus ◽

Stimulation Of

The effect of selective stimulation of splenic receptors on reflex responses of splenic and renal efferent nerves was studied in anesthetized, vagotomized, sinoaortic denervated cats. The following substances were injected into the artery or vein of vascularly isolated spleens: warm physiological saline (congestion), capsaicin (CAPS), bradykinin (BK), and norepinephrine (NE). Splenic congestion increased efferent activity of splenic and renal nerves, splenic venous pressure, systemic arterial pressure, and heart rate. CAPS and BK elicited responses similar to those produced by congestion but caused greater excitation of splenic than renal nerves. Reflex responses were eliminated by section of splenic nerves. Injection of NE increased splenic venous pressure but did not elicit reflex responses. Finally, in contrast to a previous report light- and electron-microscopic examination of splenic nerves revealed myelinated, as well as unmyelinated, fibers. These results have demonstrated that activation of splenic receptors elicits reflex cardiovascular responses and excitation of splenic and renal efferent nerves, contraction of the spleen does not produce reflex responses, the adequate stimulus for reflex responses is stretch of vessels and possibly capsule, and splenic receptors play a role in the reflex control of circulation.

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Role of ventrolateral medulla in reflex cardiovascular responses to activation of skin and muscle nerves

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.6.r1464 ◽

1995 ◽

Vol 268 (6) ◽

pp. R1464-R1471 ◽

Cited By ~ 2

Author(s):

P. Ruggeri ◽

R. Ermirio ◽

C. Molinari ◽

F. R. Calaresu

Keyword(s):

Nerve Stimulation ◽

Sural Nerve ◽

Tibial Nerve ◽

Pressor Response ◽

Cardiovascular Responses ◽

Ventrolateral Medulla ◽

Electrolytic Lesions ◽

Cardiovascular Neurons ◽

Muscle Nerve ◽

Stimulation Of

Central neuronal circuits mediating reflex cardiovascular responses to skin and muscle nerve stimulation were studied in rats under urethan anesthesia. Responses of right rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) cardiovascular neurons to stimulation of contralateral skin and muscle afferent fibers were investigated. Stimulation of the tibial (muscle) nerve excited 19 (86%) of 22 CVLM neurons and inhibited 18 (82%) of 22 RVLM neurons. Stimulation of the sural (skin) nerve excited 20 (91%) of the 22 RVLM neurons but did not affect the firing rate of any of the 22 CVLM neurons. Electrolytic lesions of the CVLM abolished the depressor responses induced by stimulation of the tibial nerve without affecting the pressor response caused by sural nerve stimulation. Similarly, reversible blockade of the CVLM by microinjection of gamma-amino-butyric acid or CoCl2 abolished the depressor response to stimulation of the tibial nerve without affecting the pressor response induced by sural nerve stimulation. These results suggest that vasodepressor responses to muscle nerve activation are mediated by a neuronal inhibitory pathway to the RVLM relayed through the CVLM.

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Double-Shock Stimulation of the Superficial Radial Nerve Compared With Standard Medial Plantar Nerve Conduction in the Early Detection of Asymptomatic Diabetic Neuropathy

Journal of Clinical Neurophysiology ◽

10.1097/wnp.0000000000000522 ◽

2018 ◽

Vol 35 (6) ◽

pp. 474-480

Author(s):

Mohamed N. Thabit ◽

Alaaeldin Sedky ◽

Mohamed A. Sayed ◽

Hemed M. Baddary ◽

Menatollah Mohamed

Keyword(s):

Early Detection ◽

Diabetic Neuropathy ◽

Nerve Conduction ◽

Radial Nerve ◽

Medial Plantar Nerve ◽

Superficial Radial Nerve ◽

Stimulation Of

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Serotonergic projection from nucleus raphe pallidus to rostral ventrolateral medulla modulates cardiovascular reflex responses during acupuncture

Journal of Applied Physiology ◽

10.1152/japplphysiol.00477.2009 ◽

2010 ◽

Vol 108 (5) ◽

pp. 1336-1346 ◽

Cited By ~ 45

Author(s):

Ali Moazzami ◽

Stephanie C. Tjen-A-Looi ◽

Zhi-Ling Guo ◽

John C. Longhurst

Keyword(s):

Blood Pressure ◽

Rostral Ventrolateral Medulla ◽

Reflex Response ◽

Ventrolateral Medulla ◽

Serotonergic Neurons ◽

Homocysteic Acid ◽

Reflex Responses ◽

Cardiovascular Reflex ◽

Raphe Pallidus ◽

Stimulation Of

We have demonstrated that stimulation of somatic afferents during electroacupuncture (EA) inhibits sympathoexcitatory cardiovascular rostral ventrolateral medulla (rVLM) neurons and reflex responses. Furthermore, EA at P5-P6 acupoints over the median nerve on the forelimb activate serotonin (5-HT)-containing neurons in the nucleus raphe pallidus (NRP). The present study, therefore, examined the role of the NRP and its synaptic input to neurons in the rVLM during the modulatory influence of EA. Since serotonergic neurons in the NRP project to the rVLM, we hypothesized that the NRP facilitates EA inhibition of the cardiovascular sympathoexcitatory reflex response through activation of 5-HT1Areceptors in the rVLM. Animals were anesthetized and ventilated, and heart rate and blood pressure were monitored. We then inserted microinjection and recording electrodes in the rVLM and NRP. Application of bradykinin (10 μg/ml) on the gallbladder every 10 min induced consistent excitatory cardiovascular reflex responses. Stimulation with EA at P5-P6 acupoints reduced the increase in blood pressure from 41 ± 4 to 22 ± 4 mmHg for more than 70 min. Inactivation of NRP with 50 nl of kainic acid (1 mM) reversed the EA-related inhibition of the cardiovascular reflex response. Similarly, blockade of 5-HT1Areceptors with the antagonist WAY-100635 (1 mM, 75 nl) microinjected into the rVLM reversed the EA-evoked inhibition. In the absence of EA, NRP microinjection of dl-homocysteic acid (4 nM, 50 nl), to mimic EA, reduced the cardiovascular and rVLM neuronal excitatory reflex response during stimulation of the gallbladder and splanchnic nerve, respectively. Blockade of 5-HT1Areceptors in the rVLM reversed the NRP dl-homocysteic acid inhibition of the cardiovascular and neuronal reflex responses. Thus activation of the NRP, through a mechanism involving serotonergic neurons and 5-HT1Areceptors in the rVLM during somatic stimulation with EA, attenuates sympathoexcitatory cardiovascular reflexes.

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