Responses of opioid and serotonin containing medullary raphe neurons to electroacupuncture

2012

Brain Research

Self Cite

Acupuncture regulates autonomic function. Our previous studies have shown that electroacupuncture (EA) at the Jianshi–Neiguan acupoints (P5–P6, underlying the median nerve) inhibits central sympathetic outflow and attenuates excitatory cardiovascular reflexes, in part, through an opioid mechanism. It is unknown if EA at these acupoints influences the parasympathetic system. Thus, using c-Fos expression, we examined activation of nucleus ambiguus (NAmb) neurons by EA, their relation to cholinergic (preganglionic parasympathetic) neurons and those containing enkephalin. To enhance detection of cell bodies containing enkephalin, colchicine (90–100 μg/kg) was administered into the subarachnoid space of cats 30 hr prior to EA or sham-operated controls for EA. Following bilateral barodenervation and cervical vagotomy, either EA for 30 min at P5–P6 acupoints or control stimulation (needle placement at P5–P6 without stimulation) was applied. While perikarya containing enkephalin were observed in some medullary nuclei (e.g., râphe), only enkephalin-containing neuronal processes were found in the NAmb. Compared to controls (n=4), more c-Fos immunoreactivity, located principally in close proximity to fibers containing enkephalin was noted in the NAmb of EA-treated cats (n=5; P<0.01). Moreover, neurons double-labeled with c-Fos and choline acetyltransferase in the NAmb were identified in EA-treated, but not the control animals. These data demonstrate for the first time that EA activates preganglionic parasympathetic neurons in the NAmb. Because of their close proximity, these EA-activated neurons likely interact with nerve fibers containing enkephalin. These results suggest that EA at the P5–P6 acupoints has the potential to influence parasympathetic outflow and cardiovascular function, likely through an enkephalinergic mechanism.

Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Nucleus ambiguus cholinergic neurons activated by acupuncture: Relation to enkephalin

Guo

2012

Brain Research

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“…EA-related restoration of blood pressure responses to cardiopulmonary reflex stimulation was not significantly influenced by blockade in the NAmb, suggesting that distinct central mechanisms and regions unique to the action of EA, such as its influence on sympathetic vasomotor centers like the RVLM and raphé nuclei in the brain stem may be involved in this aspect of EA modulation. Similar to the NAmb, GABA and opioids in the RVLM and raphé nuclei contribute to the inhibitory effects of EA on sympathoexcitatory reflex responses (12,33,40). The CVLM also regulates vasomotor tone through a GABAergic mechanism, although its importance in EA has yet to be demonstrated (30).…”

Section: Discussionmentioning

confidence: 98%

“…Thus sympathoexcitatory-induced increases in blood pressure are reduced by EA at P5-6, which overlie the median nerves (35). We have shown in a series of studies that several neurotransmitter systems, including opioids and ␥-aminobutyric acid (GABA) participate in the inhibitory influence of acupuncture (11,12,33,39). The rostral ventrolateral medulla (RVLM) and nucleus raphé pallidus (NRP) in the brain stem, which regulate sympathetic outflow, receive input from P5-6, two acupoints that exert strong cardiovascular actions (24, 28).…”

mentioning

confidence: 99%

Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and γ-aminobutyric acid

Tjen‐A‐Looi

American Journal of Physiology-Regulatory, Integrative and Comp

2012

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Stimulation of cardiopulmonary receptors with phenylbiguanide (PBG) elicits depressor cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated in part by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus (NAmb). The present study examined NAmb neurotransmitter mechanisms underlying the influence of electroacupuncture (EA) on the PBG-induced hypotension and bradycardia. We hypothesized that somatic stimulation during EA modulates PBG responses through opioid and γ-aminobutyric acid (GABA) modulation in the NAmb. Anesthetized and ventilated cats were studied during repeated stimulation with PBG or cardiac vagal afferents while low-frequency EA (2 Hz) was applied at P5-6 acupoints overlying the median nerve for 30 min and NAmb neuronal activity, heart rate, and blood pressure were recorded. Microinjection of kainic acid into the NAmb attenuated the PBG-induced bradycardia from -60 ± 11 to -36 ± 11 beats/min. Likewise, EA reduced the PBG-induced depressor and bradycardia reflex by 52 and 61%, respectively. Cardiac vagal afferent evoked preganglionic cellular activity in the NAmb was reduced by EA for about 60 min. Blockade of opioid or GABA(A) receptors using naloxone and gabazine reversed the EA-related modulation of the evoked cardiac vagal activity by 73 and 53%, respectively. Similarly, naloxone and gabazine reversed EA modulation of the negative chronotropic responses from -11 ± 5 to -23 ± 6 and -13 ± 4 to -24 ± 3 beats/min, respectively. Thus EA at P5-6 decreases PBG evoked hypotension and bradycardia as well as the NAmb PBG-sensitive preganglionic cardiac vagal outflow through opioid and GABA neurotransmitter systems.

“…Nuclei in the hypothalamus, midbrain, and medulla process this somatic input during EA to modulate sympathoexcitatory reflex responses (26,28,43). Several neurotransmitter systems, including opioids and ␥-aminobutyric acid (GABA), participate in the inhibitory influence of acupuncture on excitatory cardiovascular responses (13,17,43,46). The activity of presympathetic neurons in the rostral ventrolateral medulla (rVLM) and nucleus raphé pallidus (NRP) are modulated by EA applied to P5-6 acupoints (27,28).…”

mentioning

confidence: 99%

GABA in nucleus tractus solitarius participates in electroacupuncture modulation of cardiopulmonary bradycardia reflex

Tjen‐A‐Looi

Guo

American Journal of Physiology-Regulatory, Integrative and Comp

2014

Self Cite

Tjen-A-Looi SC, Guo ZL, Longhurst JC. GABA in nucleus tractus solitarius participates in electroacupuncture modulation of cardiopulmonary bradycardia reflex. Am J Physiol Regul Integr Comp Physiol 307: R1313-R1323, 2014. First published September 17, 2014 doi:10.1152/ajpregu.00300.2014 stimulates cardiopulmonary receptors and cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus and nucleus tractus solitarius (NTS). Electroacupuncture (EA) at P5-6 stimulates sensory fibers in the median nerve and modulates these reflex responses. Stimulation of median nerves reverses bradycardia through action of ␥-aminobutyric acid (GABA) in the nucleus ambiguus, important in the regulation of heart rate. We do not know whether the NTS or the neurotransmitter mechanisms in this nucleus participate in these modulatory actions by acupuncture. We hypothesized that somatic nerve stimulation during EA (P5-6) modulates cardiopulmonary inhibitory responses through a GABAergic mechanism in the NTS. Anesthetized and ventilated cats were examined during either PBG or direct vagal afferent stimulation while 30 min of EA was applied at P5-6. Reflex heart rate and blood pressure responses and NTS-evoked discharge were recorded. EA reduced the PBG-induced depressor and bradycardia reflexes by 67% and 60%, respectively. Blockade of GABA A receptors in the NTS reversed EA modulation of bradycardia but not the depressor response. During EA, gabazine reversed the vagally evoked discharge activity of cardiovascular NTS neurons. EA modulated the vagal-evoked cardiovascular NTS cellular activity for 60 min. Immunohistochemistry using triple labeling showed GABA immunoreactive fibers juxtaposed to glutamatergic nucleus ambiguus-projecting NTS neurons in rats. These glutamatergic neurons expressed GABA A receptors. These findings suggest that EA inhibits PBG-evoked bradycardia and vagally evoked NTS activity through a GABAergic mechanism, likely involving glutamatergic nucleus ambiguus-projecting NTS neurons. vagal excitation; phenylbiguanide; glutamic acid CLINICAL AND EXPERIMENTAL STUDIES suggest that acupuncture reduces hypertension, hypotension, and myocardial ischemia (4,11,37,41,42,51). Modulation of cardiovascular function and elevated sympathetic activity is effective with low frequency and voltage stimulation of electroacupuncture (EA) at specific acupoints P5-6 positioned to activate the underlying median nerves (44 -46). Bilateral stimulation of P5-6 acupoints activates thinly myelinated and unmyelinated sensory fibers in the median nerve and neural pathways that project to cardiovascular-related regions in the central nervous system, which regulate autonomic activity and hence hemodynamic responses (21,23,39). Nuclei in the hypothalamus, midbrain, and medulla process this somatic input during EA to modulate sympathoexcitatory reflex responses (26,28,43). Several neurotransmitter systems, including opioids and ␥-aminobutyric...