Nucleus ambiguus cholinergic neurons activated by acupuncture: Relation to enkephalin

Abstract

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.

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

“…On the other hand, opioids released during EA inhibited cardiopulmonaryinduced activation of parasympathetic outflow. We recently have shown that preganglionic cholinergic NAmb neurons activated with acupuncture are located in close proximity to enkephalinergic fibers (13). Although in this anatomical study we were unable to determine whether the EA-activated cholinergic (preganglionic) neurons were of cardiac origin (13), enkephalin is known to be present in fibers in close proximity to cardiac vagal neurons in the NAmb (4,48).…”

“…Enkephalin microinjected into the NAmb in contrast decreases HR (1). Additionally, we recently have shown that cholinergic preganglionic parasympathetic neurons in the NAmb activated by EA are situated in close proximity to fibers containing enkephalin, suggesting the potential for interaction (13). These studies suggest that modulation of NAmb neuronal activity by EA may reduce PBGinduced bradycardia and cardiac vagal-evoked activity in the NAmb, possibly through an opioid or a GABAergic mechanism.…”

Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats

“…In this regard, we recently have shown that this region participates in gastric distention-induced bradycardia associated with hypercapnia and respiratory acidosis (39). EA at P5-P6 acupoints activates NAmb neurons in close proximity to enkephalinergic processes, implying that EA exerts at least part of its cardiovascular actions through this nucleus and that enkephalin participates in EA processing in this region (13). Furthermore, we observed that EA at the P5-P6 acupoints inhibited evoked neuronal discharge in the NAmb during vagal afferent fiber stimulation (41), an action that was attenuated by blockade of GABA A receptors with gabazine.…”

Effects of Electroacupuncture on Methamphetamine‐Induced Behavioral Changes in Mice

“…Zhao et al [42] recently suggested that acupuncture at HT7, but not at PC6, reduces alcohol withdrawal effects through increasing TH mRNA and protein expression in the VTA and NAc, respectively, along with dopamine levels in the NAc. However, stimulation of PC6 can effectively treat Internet addiction [43] and alleviate the withdrawal syndrome of heroin addiction [44]; the acupoint is also involved in neurotransmitter regulation [45]. It seems compatible with the above description; ST36 has also been reported to influence opioid-induced addiction and side effects; however ST36 was not effective on the current METH study with no reports of the cocaine studies [46].…”