Selective potentiating effect of RS14203 on a serotoninergic pathway in anesthetized rats

2000 ◽  
Vol 78 (9) ◽  
pp. 708-713
Author(s):  
Chantal Savoie ◽  
Chi-Chung Chan ◽  
Ian W Rodger ◽  
Annette Robichaud
Keyword(s):  
Electrical Stimulation ◽  
Side Effects ◽  
Vagal Nerve ◽  
Nausea And Vomiting ◽  
Pulmonary Diseases ◽  
Selective Inhibitors ◽  
Anesthetized Rats ◽  
Afferent Fibers ◽  
Vagal Afferent

The usefulness of selective inhibitors of type 4 phosphodiesterase (PDE4) in the treatment of inflammation and pulmonary diseases is limited by their side effects: nausea and vomiting. We studied the effect of three structurally diverse PDE4 inhibitors on the vagal nerve afferent and efferent fibers in anesthetized rats. The effects of RS14203, (R)-rolipram, and CT-2450 were evaluated on the von Bezold-Jarisch reflex (vagal afferent fibers) and in a model of vagal electrical stimulation (vagal efferent fibers). All three PDE4 inhibitors were administered at 1, 10, or 100 µg/kg (iv) 15 min prior to the induction of bradycardia by an iv injection of 2-methyl-5-HT (von Bezold-Jarisch reflex) or by vagal electrical stimulation. At 100 µg/kg, RS14203 significantly potentiated the 2-methyl-5-HT response. No statistically significant effects were observed with (R)-rolipram or CT-2450 at the doses studied. RS14203, (R)-rolipram, or CT-2450 (1-100 µg/kg iv) did not affect the bradycardia induced by vagal electrical stimulation. Consequently, our results show that RS14203 selectively facilitates serotoninergic neurotransmission in vagal afferent fibers. The emetic action of RS14203 may be mediated by this mechanism.Key words: PDE4 inhibitors, von Bezold-Jarisch reflex, emesis, vagal afferent and efferent fibres, bradycardia.

Responses of medullary raphe neurons to electrical and chemical activation of vagal afferent nerve fibers

1993 ◽  
Vol 70 (5) ◽  
pp. 1950-1961 ◽  
Author(s):  
A. R. Evans ◽  
R. W. Blair
Keyword(s):  
Electrical Stimulation ◽  
Chemical Activation ◽  
Vagal Afferents ◽  
Frequency Dependent ◽  
Afferent Fibers ◽  
Vagal Afferent ◽  
Mixed Responses ◽  
Excitatory Responses ◽  
Dose Dependent ◽  
Stimulation Of

1. Various intensities, frequencies, and pulse widths of electrical stimulation of vagal afferent fibers were used to assess the responses of 87 medullary raphe neurons to vagal afferent fiber input in pentobarbital sodium-anesthetized, barodenervated paralyzed cats. Thirty-seven neurons were antidromically activated from the T2-T3 segments of the thoracic spinal cord, and 40 neurons could not be antidromically activated. Neurons were located in the nucleus raphe magnus (79%) and the nucleus raphe obscurus (15%). The remaining 6% of the neurons were not found; however, their locations were comparable in depth and position on the midline with other neurons in the same animals whose locations were identified. 2. The responses of 60 neurons to electrical stimulation of vagal afferent fibers were classified as excitatory (38%), inhibitory (24%), or mixed, (7%). The mixed responses were characterized by excitation at one frequency or intensity and inhibition at another frequency or intensity. The remaining 27 neurons did not clearly respond. 3. The excitatory responses to electrical stimulation of the cervical vagus nerve were intensity and frequency dependent. Inhibitory responses were frequency dependent at lower frequencies of stimulation and both frequency and intensity dependent at higher frequencies. The mixed responses were frequency dependent. Overall, longer pulse widths produced significantly greater responses than shorter pulse widths. 4. Thirty-three neurons were tested for responses to chemical stimulation of vagal afferents with intra-atrial injections of three doses of veratridine. Twenty-one percent were excited, 55% were inhibited, and 6% had mixed responses. For the mixed responses, excitation occurred at one dose and inhibition at another. The remaining 18% of the neurons were unresponsive to veratridine. The excitatory responses were dose dependent, but the inhibitory responses were not. Three doses of phenybiguanide (PBG) were also used to chemically activate vagal afferents in 27 neurons. Eleven percent were excited, 44% were inhibited, and 4% had mixed responses. The remaining 41% were unresponsive to PBG. The excitatory and inhibitory responses were dose dependent. 5. When comparing responses in projection and nonprojection neurons, inhibition was seen significantly more often in projection neurons and excitation in nonprojection neurons. Sixty-three percent of the neurons inhibited by electrical stimulation were raphespinal neurons, and 78% of the neurons excited by vagal stimulation were nonprojection neurons. Similar observations were made with the responses to chemical activation of the vagus. 6. Neurons with lower spontaneous discharge rates were more often excited by vagal stimulation and neurons with higher rates were more often inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

Vagal afferent inhibition of primate thoracic spinothalamic neurons

1983 ◽  
Vol 50 (4) ◽  
pp. 926-940 ◽  
Author(s):  
W. S. Ammons ◽  
R. W. Blair ◽  
R. D. Foreman
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Background Activity ◽  
Linear Regression Analysis ◽  
Cell Activity ◽  
High Threshold ◽  
Thoracic Spinal Cord ◽  
Afferent Fibers ◽  
Vagal Afferent ◽  
Stimulation Of

Spinothalamic (ST) neurons in the C8-T5 segments of the spinal cord were examined for responses to electrical stimulation of the left thoracic vagus nerve (LTV). Seventy-one ST neurons were studied in 39 anesthetized monkeys (Macaca fascicularis). Each neuron could be excited by manipulation of its somatic field and by electrical stimulation of cardiopulmonary sympathetic afferent fibers. LTV stimulation resulted in inhibition of the background activity of 43 (61%) ST neurons. Nine (13%) were excited, 3 (4%) were excited and then inhibited, while 16 (22%) did not respond. There was little difference among these groups in terms of the type of somatic or sympathetic afferent input although inhibited cells tended to be more prevalent in the more superficial laminae. The degree of inhibition resulting from LTV stimulation was related, in a linear fashion, to the magnitude of cell activity before stimulation. LTV inhibition of background activity was similar among wide dynamic range, high threshold, and high-threshold cells with inhibitory hair input. Any apparent differences in LTV inhibitory effects among these groups were accounted for by the differences in ongoing cell activity as predicted by linear regression analysis. LTV stimulation inhibited responses of 32 of 32 ST cells to somatic stimuli. In most cases the stimulus was a noxious pinch; however, LTV stimulation also inhibited responses to innocuous stimuli such as hair movement. Bilateral cervical vagotomy abolished the inhibitory effect of LTV stimulation on background activity (six cells) or responses to somatic stimuli (seven cells). Stimulation of the cardiac branch of the vagus inhibited activity of three cells to a similar degree as LTV stimulation, while stimulation of the vagus below the heart was ineffective in reducing activity of 10 cells. We conclude that LTV stimulation alters activity of ST neurons in the upper thoracic spinal cord. Vagal inhibition of ST cell activity was due to stimulation of cardiopulmonary vagal afferent fibers coursing to the brain stem, which appear to activate descending inhibitory spinal pathways. Vagal afferent activity may participate in processing of somatosensory information as well as information related to cardiac pain.

scholarly journals Transcutaneous Electrical Acupoint Stimulation Reduces Postoperative Analgesic Requirement in Patients Undergoing Inguinal Hernia Repair: A Randomized, Placebo-Controlled Study

2021 ◽  
Vol 10 (1) ◽  
pp. 146
Author(s):  
Mateusz Szmit ◽  
Siddarth Agrawal ◽  
Waldemar Goździk ◽  
Andrzej Kübler ◽  
Anil Agrawal ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Inguinal Hernia ◽  
Side Effects ◽  
Hernia Repair ◽  
Inguinal Hernia Repair ◽  
Adverse Drug Events ◽  
Controlled Trial ◽  
Controlled Study ◽  
Anesthetic Technique ◽  
Analgesic Requirement

Given the rising rate of opioid-related adverse drug events during postsurgical pain management, a nonpharmacologic therapy that could decrease analgesic medication requirements would be of immense value. We designed a prospective, placebo-and-randomized controlled trial to assess the clinical effect of transcutaneous acupoint electrical stimulation (TEAS) on the postoperative patient-controlled analgesia (PCA) requirement for morphine, as well as side effects and recovery profile after inguinal hernia repair. Seventy-one subjects undergoing inguinal hernia repair with a standardized anesthetic technique were randomly assigned to one of three analgesic treatment regimens: PCA + TEAS (n = 24); PCA + sham-TEAS (no electrical stimulation) (n = 24), and PCA only (n = 23). The postoperative PCA requirement, pain scores, opioid-related side effects, and blood cortisol levels were recorded. TEAS treatment resulted in a twofold decrease in the analgesic requirement and decreased pain level reported by the patients. In addition, a significant reduction of cortisol level was reported in the TEAS group at 24 h postoperatively compared to the sham and control groups. We conclude that TEAS is a safe and effective option for reducing analgesic consumption and postoperative pain following inguinal hernia repair.

scholarly journals Seminal Plug Expulsion Induced by Electrical Stimulation of the Intermesenteric Nerve in Anesthetized Rats

2007 ◽  
Vol 77 (4) ◽  
pp. 717-722 ◽  
Author(s):  
Jacques Bernabé ◽  
Pierre Clément ◽  
Pierre Denys ◽  
Laurent Alexandre ◽  
François Giuliano
Keyword(s):  
Electrical Stimulation ◽  
Anesthetized Rats ◽  
Stimulation Of
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